Randomized Explanatory Trial of a Mediterranean Dietary Pattern Weight Loss Intervention for Primary Care Practices
Phase: NA
Conditions: Weight Loss, Diet, Healthy, Cardiovascular Risk Factor
Sponsor: University of North Carolina, Chapel Hill

PROTOCOL 
 
 
Randomized Explanatory Trial of a Mediterranean Dietary Pattern 
Weight Loss Intervention for Primary Care Practices 
 
 
 
NCT number NCT04302727 
Document Date 06/08/2025 
 

 
 
 
Randomized Explanatory Trial of a Mediterranean Dietary Pattern Weight Loss 
Intervention for Primary Care Practices 
(Brief Title:  Med-South Weight Loss RCT) 
Protocol Number: 1.2 
National Clinical Trial (NCT) Identified Number: NCT04302727 
Principal Investigators:  Thomas C. Keyserling, MD, MPH and Carmen Samuel 
Hodge, PhD, MS, RD 
Sponsor: Center for Health Promotion and Disease Prevention (a CDC funded 
Prevention Research Center) at the University of North Carolina at Chapel Hill.  
Grant Title: Randomized Explanatory Trial of a Mediterranean Dietary Pattern 
Weight Loss Intervention for Primary Care Practices 
Grant Number: 1R61HL142680-01A1 
Funded by: National Heart Lung and Blood Institute 
Version Number:  v.1.9 
Version 1.9: 8 June 2025 
 
 

ii 
 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be published or disclosed without prior 
approval of the Principal Investigator or other participating study leadership and as consistent with the 
NIH terms of award.  
 
 
 
 
 
 
 

 
 
3 
 
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
INVESTIGATOR’S SIGNATURE .............................................................................................................................. 2 
1 
PROTOCOL SUMMARY ............................................................................................................................... 3 
1.1 
Synopsis ................................................................................................................................................ 3 
1.2 
Schema ................................................................................................................................................. 4 
1.3 
Schedule of Activities .......................................................................................................................... 6 
2 
INTRODUCTION ............................................................................................................................................ 7 
2.1 
Study Rationale .................................................................................................................................... 8 
2.2 
Background........................................................................................................................................... 8 
2.3 
Risk/Benefit Assessment .................................................................................................................. 11 
2.3.1 
Known Potential Risks ...................................................... Error! Bookmark not defined. 
2.3.2 
Known Potential Benefits .............................................................................................. 12 
2.3.3 
Assessment of Potential Risks and Benefits .............................................................. 12 
3 
OBJECTIVES AND ENDPOINTS .............................................................................................................. 12 
4 
STUDY DESIGN ........................................................................................................................................... 14 
4.1 
Overall Design .................................................................................................................................... 14 
4.2 
Scientific Rationale for Study Design.............................................................................................. 14 
4.3 
Justification for Intervention ............................................................................................................. 15 
4.4 
End-of-Study Definition ..................................................................................................................... 15 
5 
STUDY POPULATION ................................................................................................................................ 15 
5.1 
Inclusion Criteria ................................................................................................................................ 15 
5.2 
Exclusion Criteria ............................................................................................................................... 16 
5.3 
Lifestyle Considerations .................................................................................................................... 18 
5.4 
Screen Failures .................................................................................................................................. 18 
5.5 
Strategies for Recruitment and Retention ...................................................................................... 19 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ............................................ 28 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration ...................................... 28 
6.1.1 
Study Intervention or Experimental Manipulation Description ................................. 28 
6.1.2 
Administration and/or Dosing ....................................................................................... 33 
6.2 
Fidelity ................................................................................................................................................. 38 
6.2.1 
Interventionist Training and Tracking .......................................................................... 39 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 39 
6.4 
Study Intervention/Experimental Manipulation Adherence.......................................................... 40 
6.5 
Concomitant Therapy ........................................................................................................................ 40 
6.5.1 
Rescue Therapy ............................................................................................................. 40 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ......................................................................................... 41 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ............................................. 41 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 41 
7.3 
Lost to Follow-Up ............................................................................................................................... 42 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 42 
8.1 
Endpoint and Other Non-Safety Assessments .............................................................................. 43 
8.2 
Safety Assessments .......................................................................................................................... 72 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 73 
8.3.1 
Definition of Adverse Events ........................................................................................ 73 
8.3.2 
Definition of Serious Adverse Events .......................................................................... 73 

 
 
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8.3.3 
Classification of an Adverse Event .............................................................................. 73 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 75 
8.3.5 
Adverse Event Reporting .............................................................................................. 76 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 76 
8.3.7 
Reporting Events to Participants ................................................................................. 76 
8.3.8 
Events of Special Interest ............................................................................................. 77 
8.3.9 
Reporting of Pregnancy ................................................................................................ 77 
8.4 
Unanticipated Problems .................................................................................................................... 77 
8.4.1 
Definition of Unanticipated Problems .......................................................................... 77 
8.4.2 
Unanticipated Problems Reporting .............................................................................. 77 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 78 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 78 
9.1 
Statistical Hypotheses ....................................................................................................................... 78 
9.2 
Sample Size Determination .............................................................................................................. 79 
9.3 
Populations for Analyses .................................................................................................................. 80 
9.4 
Statistical Analyses............................................................................................................................ 80 
9.4.1 
General Approach .......................................................................................................... 80 
9.4.2 
Analysis of the Primary Endpoint(s) ............................................................................ 80 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 81 
9.4.4 
Safety Analyses .............................................................................................................. 82 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 82 
9.4.6 
Planned Interim Analyses ............................................................................................. 82 
9.4.7 
Sub-Group Analyses ..................................................................................................... 82 
9.4.8 
Tabulation of Individual Participant Data .................................................................... 83 
9.4.9 
Exploratory Analyses ..................................................................................................... 83 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 83 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 83 
10.1.1 
Informed Consent Process ........................................................................................... 83 
10.1.2 
Study Discontinuation and Closure ........................................................................... 117 
10.1.3 
Confidentiality and Privacy ......................................................................................... 117 
10.1.4 
Future Use of Stored Specimens and Data ............................................................. 118 
10.1.5 
Key Roles and Study Governance ............................................................................ 119 
10.1.6 
Safety Oversight ........................................................................................................... 119 
10.1.7 
Clinical Monitoring ........................................................................................................ 122 
10.1.8 
Quality Assurance and Quality Control ..................................................................... 122 
10.1.9 
Data Handling and Record Keeping .......................................................................... 126 
10.1.10 
Protocol Deviations ...................................................................................................... 126 
10.1.11 
Publication and Data Sharing Policy ......................................................................... 129 
10.1.12 
Conflict of Interest Policy ............................................................................................ 130 
10.2 
Additional Considerations ............................................................................................................... 130 
10.3 
Abbreviations and Special Terms ................................................................................................. 130 
10.4 
Protocol Amendment History ......................................................................................................... 132 
11 
REFERENCES ........................................................................................................................................... 134 
 

 
 
 
1 
STATEMENT OF COMPLIANCE 
 
(1) [The trial will be carried out in accordance with International Council on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 
46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812).  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
 
 
For either option above, the following paragraph would be included: 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the IRB for review and approval. Approval of both the protocol and the consent 
form(s) must be obtained before any participant is consented. Any amendment to the protocol 
will require review and approval by the IRB before the changes are implemented to the study. All 
changes to the consent form(s) will be IRB approved; a determination will be made regarding 
whether a new consent needs to be obtained from participants who provided consent, using a 
previously approved consent form.] 
 
 

 
 
 
2 
INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances 
that this study will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable US 
federal regulations and ICH guidelines, as described in the Statement of Compliance above. 
 
Principal Investigator or Clinical Site Investigator: 
Signed: 
Thomas C. Keyserling 
Date: 
1/23/20/updated 
review 6/8/25 
 
Name*:  Thomas C. Keyserling, MD MPH 
 
Title*: Professor of Medicine 
 
Investigator Contact Information 
Affiliation*:  Center for Health Promotion and Disease Prevention (a CDC funded Prevention Research 
Center) at the University of North Carolina at Chapel Hill. 
Address: 1700 Martin Luther King, Jr BLVD   Chapel Hill, NC 27599 
Telephone:  919-966-6081 
Email: jato@med.unc.edu 
 
[For multi-site studies, the protocol should be signed by the clinical site investigator who is responsible 
for the day to day study implementation at his/her specific clinical site.] 
Signed: 
 
Date: 
 
 
Name:  
 
Title: 
 
 
Affiliation: 
 
 
 
 
 

 
 
 
3 
1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
 
Title: 
Randomized Explanatory Trial of a Mediterranean Dietary Pattern 
Weight Loss Intervention for Primary Care Practices 
Grant Number: 
1R61HL142680-01A1 
Study Description: 
The US Preventive Services Task Force recommends primary care 
patients be screened for obesity and those with a body mass index 
(BMI) ≥30 kg/m2 receive an intensive, multi-component behavioral 
weight loss intervention. However, the effectiveness of weight loss 
interventions implemented in primary care settings has been limited. 
Also, most weight loss programs have not promoted a dietary pattern 
associated with reduced rates for cardiovascular (CVD) and other 
chronic diseases such as a Mediterranean (Med)-style eating pattern.  
 
The DELISH (Delicious Eating for Life in Southern Homes) Study will test 
if a weight loss intervention emphasizing a healthful eating pattern 
(Med-style) can yield long-term weight loss and improved CVD risk 
profiles. Patients will be recruited from 5-8 primary care practices 
located in the Chapel Hill area and in eastern NC. Study participants will 
be randomized to the Med-Style Weight Loss Intervention or 
Augmented Usual Care (Weight Watchers™). The interventions are 
given free of charge. Study measurement visits are at baseline and 4, 
12, and 24 month follow-up. 
 

 
 
 
4 
Objectives*: 
 
Primary Aim (efficacy):  Weight loss at 24 months.  Hypothesis: Mean 
weight loss in the intervention group will exceed that in augmented 
usual care by ≥ 4% of initial body weight (e.g., ≥ 5% intervention, ~1% 
control). 
Secondary weight outcomes:  Assess difference between study groups 
in proportion losing ≥ 5% body weight and differences in mean 
weight loss and proportion losing ≥ 5% across 3 pre-specified 
subgroups: 1) with vs. without diabetes; 2) females vs. males; and 3) 
Whites vs. African Americans. 
Secondary Aim 1—Physiologic and Lifestyle Outcomes:  Assess change 
in blood pressure, A1c, markers of inflammation, skin carotenoids, 
and self-reported dietary patterns by study group. 
Secondary Aim 2—Process and Psychosocial Factors:  Assess process 
variables (attendance, fidelity, and acceptability of the Med-style 
dietary intervention), and key behavioral and psychosocial variables, 
including self-regulation/monitoring skills, self-efficacy, motivation, 
and quality of life. 
Secondary Aim 3--Economic Outcomes:  Assess implementation cost, 
and incremental cost-effectiveness of the intervention relative to 
control in terms of cost per percentage reduction in weight (i.e., kg 
lost) and cost per quality adjusted life years (QALYs) gained. 
Exploratory Outcome—Stool Microbiome:  Assess change in stool 
microbiome in response to the interventions.  
Endpoints*: 
As outlined above under aims.  
Study Population: 
Participants will be enrolled in central and eastern North Carolina.  The 
overall sample size is 360. We will conduct contemporaneous 
enrollment of sub-groups to ensure that at least 40% of participants 
will be African American, diagnosed with diabetes, and male.  
Phase* or Stage: 
Phase III  
Description of 
Sites/Facilities Enrolling 
Participants: 
Participants will be recruited from the UNC Department of Medicine 
Internal Medicine Clinic in Chapel Hill, at least 2 community practices 
within 20 miles of Chapel Hill, and at least 2 community practices from 
eastern North Carolina.  
 
Description of Study 
Intervention/Experimental 
Manipulation: 
The study intervention promotes a Mediterranean-style diet 
throughout the 2 year intervention period. (We use Mediterranean-
style diet as a commonly recognized term for an evidence-informed 
dietary pattern--the intervention is Mediterranean Style, adapted for 
the southeastern US and informed by current evidence on dietary 
patterns and health outcomes).  The Intervention has multiple contacts 
with study participants as outlined below. Format is individual 
counseling, face-to-face and phone, with the latter supported by web-
based shared screen technology.  
Study Duration*: 
42 months  
Participant Duration: 
24 months 
1.2 
SCHEMA  

 
 
 
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1.3 
SCHEDULE OF ACTIVITIES  
 
The schedule of study activities is outlined in the flow diagram below.  Please note, this diagram was 
prepared January, 2020 and is correct for Phase I study activities.  As of January, 2020, Phases II and III 
are still being refined. These phases will be undated in Version 2 (for Phase II) and Version 3 (Phase III) of 
this protocol document.  Also, please note the following study activities prior to Baseline Measures. 
 
Recruitment and Enrollment will occur during two phone calls. 
• 
Eligibility phone call.  Patients who are referred to the study by their primary care provider will 
be called to assess interest and eligibility.  Anticipated call duration is 10-15 minutes.  If 
interested and eligible, the potential participant will be sent the study consent form and asked 
to review before the consent phone call. 
• 
Consent phone call.  This call is planned for 1-2 weeks after the eligibility call and is expected to 
last 20 to 30 minutes.  Study staff will review the study in detail going over each key component 
of the consent form. If the potential participant agrees to participate, he/she will be invited to 
document consent through an IRB approved e-consent process.  If the participant does not wish 
to use e-consent, he/she will give verbal consent and will sign the consent form at the 
enrollment visit, depicted on the diagram as “baseline measures.”  Note, the IRB has granted 
the study a waiver to collect baseline questionnaire data based on verbal consent. After the 
consent phone call, those who agree to participate will be encouraged to complete baseline 
questionnaires on-line (using REDCap) or by phone before the enrollment visit.  
 
Allowable window for measurement and counseling visits. 
• 
Allowable widows for measurement visits. 
o 4 month:  3-8 months. 
o 12 months: 11-18. 
o 24 months: 23-30. 
• 
Allowable visits for counseling visits.  
o See flow diagram for sequence.  The sequence will be followed as in the flow diagram.  If 
a participant is falling behind the timeline, counseling visits may need to be truncated to 
allow the appropriate next measurement visit to occur within the allowable window.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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2 
 
INTRODUCTION 
 

 
 
 
8 
2.1 
STUDY RATIONALE  
Note: the text for sections 2.1 and 2.2 is presented in Section 2.2  
 
2.2 
BACKGROUND  
 
2.2a. “Explain importance of the problem or critical barrier to progress that the proposed project 
addresses.” 
 
Among adults with obesity, modest weight loss can prevent or delay the onset of diabetes, improved 
glycemic control in those with diabetes, and improve other physiologic risk factors for cardiovascular 
disease (CVD).1, 2 Accordingly, the US Preventive Services Task Force (hereafter, called the “Task Force”) 
recommends that primary care clinicians screen all adults for obesity and offer or refer those with a BMI 
≥ 30 kg/m2 to intensive behavioral weight loss interventions.2 In formulating this recommendation, the 
Task Force “found adequate evidence that intensive, multicomponent behavioral interventions for 
obese adults can lead to an average weight loss of 4 to 7 kg (8.8 to 15.4 pounds).2   
 
Despite the Task Force guideline endorsing intensive weight loss interventions, the effectiveness of 
weight loss interventions has been limited in both primary care and community settings. In a recent 
meta-analysis by Booth3 assessing behavioral weight loss programs delivered in primary care settings, 
pooled results across 15 randomized controlled trials (RCTs) demonstrated only modest weight loss at 
12 (-1.4 kg, 95% CI -2.1 to -0.6) and 24 month follow-up (-1.2 kg, 95% CI -2.3 to -0.2). Weight loss was 
also modest at 12 month follow-up (-2.2 kg, 95%CI -2.9 to -1.4) in a recent meta-analysis of 5 studies 
assessing commercial weight loss programs.4  In his review on weight loss in primary care settings, 
Wadden5 suggests primary care-based weight loss interventions often fail due to inadequate intensity 
for successful weight loss.  
 
Weight loss is difficult to achieve and hard to sustain, especially for vulnerable patients (racial/ethnic 
minorities, rural patients, residents of the South) who are more likely to be obese, yet have been 
underrepresented in weight loss intervention studies.6 Those with diabetes have an even harder time 
losing weight and maintaining weight loss.7 This is especially true for African American women with type 
2 diabetes.6    
 
Emerging paradigms of care provide a framework for more effective clinic-based weight loss 
interventions. If an intervention is going to be implemented and sustained in routine primary care 
practice settings, its intensity should be aligned with practice staffing and it should be reimbursed. 
Wadden5 suggests a team approach is needed to provide the requisite intensity (frequency and amount 
of contact time) for successful weight loss. He notes physicians typically do not have the time or training 
to give counseling, which might better be given by other staff (e.g., registered dietitians, medical 
assistants, nurses, etc.) -- the type of staff currently employed by patient centered medical homes 
(PCMHs).8 Over 12,000 practices have PCMHs,9 which have been shown to reduce the cost of care and10, 
11 improve care management for chronic diseases11 including diabetes;12 thus, they offer promise as a 
venue to deliver successful weight loss interventions.  
 

 
 
 
9 
Most weight loss interventions assessed in RCTs conducted in the US have NOT focused on promoting 
a healthful dietary pattern associated with reduced CVD events and total mortality. The Task Force 
“found inadequate direct evidence about the effectiveness of these (weight loss) interventions on long-
term health outcomes (for example, death, CVD, and hospitalizations).”2 Notably, most weight loss trials 
in the US have tested a low-fat dietary pattern,1, 13-16 which is not associated with decreased CVD risk17, 18 
and is difficult to maintain over time.17  With the publication of the PREDIMED RCT main results in 
201319 (see information on retraction20 and republication in June, 2018,21 Sec. 1.2d), which 
demonstrated a 30% reduction in CVD events among those following a Mediterranean-style (Med-style) 
dietary pattern in Spain, there has been an increasing appreciation that a Med-style  dietary pattern (or 
more generally, a healthful dietary pattern that includes generous consumption of high-quality fats22, 23 
and carbohydrates,24-26) is associated with improved health outcomes27-29 including a reduction in CVD 
events and premature mortality.  
 
Thus, the major problems that this proposal addresses are: 1) the limited efficacy of previously tested 
weight loss interventions conducted in primary care settings, 2) the lack of weight loss interventions that 
also promote a healthful dietary pattern, and 3) the scarcity of previously evaluated and effective weight 
loss interventions tailored to the needs of vulnerable patients. 
 
2.2b. “Describe the scientific premise for the proposed project, including consideration of the strengths 
and weaknesses of published research.”  In this section, we address: 1) strengths and weaknesses of the 
Task Force recommendation for primary care clinicians to recommend weight loss interventions, 2) 
rationale for developing and testing a weight loss intervention promoting a Med-style dietary pattern, 
and 3) strengths and weaknesses of the literature on the efficacy of weight loss interventions promoting 
a Med-style dietary pattern.   
 
Strengths and weaknesses of the Task Force guidelines recommending intensive weight loss 
interventions in primary care settings for patients who are obese. In the evidence review1 for the Task 
Force, 21 behavioral weight loss studies with 12 to 18 month follow-up were included. The mean weight 
loss was 3.0 kg (95% CI, 2.0 to 4.0), but only 5 were conducted in primary care settings and only 2 of 
these in the US. Thus, more research on weight loss interventions given in US primary care practice 
settings is needed. 
 
Rationale for developing and testing a weight loss intervention promoting a healthful dietary pattern. 
The Task Force weight loss recommendations apply to patients with and without diabetes. The 
prevalence of diabetes in the US is 9.4%, 25% in those over 65, and almost twice as common among 
African Americans.30 As patients with diabetes are seen in clinic often, they account for ~40% of adult 
clinic visits in primary care.31 In addition, about 1/3 of US adults have pre-diabetes (A1c 5.7-6.4%).30 
Because patients with diabetes and pre-diabetes are generally obese,32 most patients seen in primary 
care who qualify for an intensive weight loss intervention per Task Force guidelines have diabetes or 
pre-diabetes. Adults with diabetes are about 2 times more likely to have a heart attack or stroke33, 34 
than the general population and those with pre-diabetes35 and obesity without diabetes36 are also at 
increased CVD risk. Thus, weight loss interventions should also target CVD risk reduction. Extending this 
further, weight loss interventions should strive to reduce premature mortality. These considerations 
represent a paradigm shift from the goal of weight loss to a goal of weight loss with a concomitant 
reduction in chronic diseases and premature mortality. This paradigm shift is supported by the emerging 
literature on dietary patterns and health outcomes,19, 26, 28, 29, 37, 38 discussed in more detail below. 
 

 
 
 
10 
Why the Diabetes Prevention Program (DPP) dietary pattern may no longer be appropriate for a 
weight loss intervention. The DPP RCT15 was a key proof-of-concept study providing strong evidence 
that a lifestyle intervention promoting weight loss can reduce diabetes incidence. Because of this 
important finding, the DPP lifestyle program has received a strong endorsement from federal,39, 40 health 
professional,41 and volunteer organizations42 as an evidence-informed weight loss program for patients 
with or at risk for type 2 diabetes and is currently considered a standard of care. However, the dietary 
pattern advocated by this program43 was developed in the 1990s44 and one of its primary goals is a 
reduction in total fat. As noted in the next paragraph, there is now an emerging consensus that regular 
consumption of high-quality dietary fat is a key component of a healthful dietary pattern.22, 23 Thus, the 
DPP weight loss intervention45 advocating a low-fat diet runs counter to current scientific knowledge.19, 
22  Further, there is high-quality evidence from 2 large, well-conducted RCTs in those with and without 
diabetes that a low-fat dietary pattern does not reduce CVD risk.  Look AHEAD, designed to see if a DPP-
like weight loss intervention would reduce CVD events in overweight or obese patients with diabetes, 
was stopped early for futility16 while the low-fat dietary intervention arm in the Women’s Health 
Initiative RCT also failed to reduce CVD events.17   
 
What type of dietary pattern should be advocated as part of a weight loss intervention?  The 
PREDIMED RCT19 compared a Med-style dietary pattern supplemented with olive oil or nuts to a control 
diet (lower fat diet) and observed a 30% reduction in major CVD events in the intervention arms, with a 
similar reduction in risk for the 49% (n=3614) participants with type 2 diabetes. Moreover, the 
intervention in this trial was associated with a 30% decrease in risk of developing diabetes,46, 47 despite 
only minimal weight loss.48 (In June, 2018, the PREDIMED primary outcomes paper19 was retracted20 due 
to recognized irregularities with randomization, and was republished.21 After “omission of 1588 
participants whose study-group assignments were known or suspected to have departed from the 
protocol,” the findings were unchanged.) Though some will question the PREDIMED findings given the 
recognized irregularities,49 it is important to note a prior secondary prevention RCT noted similar 
favorable results50-52 and multiple well-conducted observational studies have associated healthful 
dietary patterns characterized by increased intake of high-quality fats38 and high-quality 
carbohydrates24-26 with reduced CVD risk, reduced premature mortality, and increased life-expectancy.53 
Indeed, a recent systematic review and meta-analysis of cohort studies27 estimated that a healthful 
dietary pattern is “associated with a significant reduction in the risk of all-cause mortality, CVD, cancer, 
type 2 diabetes, and neurodegenerative disease by 22%, 22%, 16%, 18%, and 15%, respectively.” 
 
Healthful dietary patterns were highlighted in a recent publication29 showing that those who changed to 
or followed more healthful patterns over time, as assessed by the Alternate Healthy Eating Index 
Score,54 the Alternate Mediterranean Diet Score,55 or the DASH score56 had lower all-cause mortality. 
The dietary patterns rated highly by the Alternate Mediterranean Diet Score55 and Alternate Healthy 
Eating Index54, 57 are generally similar and do not focus on fat restriction, as does the DASH diet.58, 59  
Because the health benefits of a Med-style pattern are further supported by RCT evidence,21, 50-52, 60 (the 
other patterns have not been studied to clinical outcomes in RCTs) we will advocate this general dietary 
pattern in our intervention, calling it Med-South, while recognizing this pattern could more generally be 
termed a healthful dietary pattern. As outlined in Sec. 3.3a, our operationalization of the Med-diet 
aligns extremely well with that described as evidence-based in a recent review by Mozaffarian61 entitled, 
“Dietary and Policy Priorities for CVD, Diabetes and Obesity.” 
 
What type of dietary pattern should be advocated for maintenance of weight loss? There is an 
increasing appreciation that dietary composition impacts energy expenditure during weight loss 
maintenance and thus maintenance of weight loss.62-65 In mechanistic weight loss studies, low glycemic 

 
 
 
11 
index and low carbohydrate patterns are associated with less reduction in resting energy expenditure.62, 
63 In support of this formulation are the long-term (6 year follow up) weight loss findings from the 
DIRECT RCT,66, 67 with weight loss maintained in the Med-style and low-carb study arms (greatest in 
Med-style), but not in the low-fat arm. These data speak to the importance of attention to dietary 
composition in support of weight loss maintenance.   
 
What are the strengths and weaknesses of the current literature on the efficacy of weight loss 
interventions promoting a Med-style dietary pattern? This topic was addressed in a recent systematic 
review (2016).68  (Note, we conducted a PubMed search on 6/24/18 using the term “Mediterranean Diet 
Weight Loss” and did not identify other relevant RCTs conducted in the US, beyond those included in 
this review.)  The authors reviewed 5 studies66, 69-72 and concluded that the Mediterranean diet resulted 
in greater weight loss at ≥ 12 months than a low-fat diet and similar weight loss as other comparator 
diets (low-carb66 and low-carb Mediterranean69). Three of these studies report weight loss at 24 months, 
with the Med-style interventions yielding ≥ 4 kg weight loss at this follow-up interval. However, the 
relevance of these 5 studies to obese patients in the US referred for weight loss by their primary care 
clinician is questionable. Two were conducted in Israel66, 69 and one in Italy,73 where the baseline dietary 
pattern is quite different from the US. The 2 US studies enrolled: 1) a sample from Boston, MA via letters 
to primary care physicians and posted flyers (82% white)71 and 2) patients who had a myocardial 
infarction within the prior 6 weeks in Spokane, WA (98% white).72  To our knowledge, no RCT has been 
conducted in the US on a primary care clinic enrolled multi-ethnic population that has tested a Med-
style dietary pattern intervention for weight loss efficacy. 
 
Thus, there is a strong scientific premise in support of conducting an RCT enrolling multi-ethic 
participants referred by primary care clinicians per Task Force guidelines to assess the efficacy of a 
weight loss intervention that promotes a Med-style dietary pattern adapted for Americans. 
 
2.2c. “Explain how the proposed project will improve scientific knowledge, technical capability, and/or 
clinical practice in one or more broad fields.”   If successful, the findings from this study could have a 
significant impact on the challenge of managing obesity in primary care settings. Our findings will 
improve scientific knowledge and technical capacity to promote weight loss in a manner consistent with 
the emerging paradigm that weight loss studies should promote health behaviors associated with 
weight loss AND a decreased risk for CVD events and premature mortality. 
2.3 
RISK/BENEFIT ASSESSMENT  
 
The potential risks of participating in this study are few.  In the PREDIMED randomized trial,20 there were 
no adverse reported outcomes related to the diet intervention.  Similarly, in our recent Heart Healthy 
Lenoir study74, 75 there were no reported adverse outcomes felt to be related to the dietary intervention. 
In this study, moderate physical activity will be recommended for both intervention groups. In terms of 
physical risk, it is unlikely that the recommended moderate intensity physical activity will provoke 
underlying medical conditions such as asthma, coronary heart disease, or musculoskeletal disease. 
Further, we will provide information on what to do if participants experience pain or other problems 
when being active. We will also provide explicit instructions to promote safety when walking for physical 
activity on streets or near highways. In addition, the risks of phlebotomy, though uncommon, include 
pain, fainting, local bruising, and infection at the puncture site. We do not foresee significant 
psychological, financial, legal or other risks from participation in this research study.  
 

 
 
 
12 
2.3.1 KNOWN POTENTIAL BENEFITS  
 
Cardiovascular disease (CVD) is the most common cause of mortality for patients with obesity and 
diabetes and rates of CVD are high for obese patients with diabetes. There are high quality data 
suggesting that adhering to a Mediterranean style dietary pattern is associated with a substantial 
reduction in risk from heart disease and stroke. In addition, weight loss improves cardiometabolic risk 
factors and leads to other improved outcomes such as increased mobility, less joint pain, and less sleep 
apnea. Although participants in the study may not personally benefit over the relatively short time 
frame of the study, if they are able to maintain their lifestyle change, they may benefit over time. 
 
Our hypothesis is that those who are randomized to the Med-South Weight Loss Program may benefit 
more than those randomized to WW, based on our expectation of greater sustained weight loss and 
greater improvement in traditional CVD risk factors such as blood pressure and blood lipids and 
emerging risk factors including markers of inflammation.  That said, we anticipate those randomized to 
WW will experience some weight loss and improvement in risk factors.   
2.3.2 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
The potential risks are small, as noted above.  We outline our approach to minimizing risk above. We 
believe there is much to be gained from this study, especially in the context of minimal risk.  
 
3 
OBJECTIVES AND ENDPOINTS  
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
PUTATIVE 
MECHANISMS OF 
ACTION 
Primary 
 
 
 
Primary Aim (efficacy):  
Weight loss at 24 months.  
Hypothesis: Mean weight 
loss in the intervention 
group will exceed that in 
augmented usual care by ≥ 
4% of initial body weight 
(e.g., ≥ 5% intervention, 
~1% control). 
 
 
Weight change. 
(clarification: 
primary outcome 
is % weight 
change. Weight 
change in Kg will 
be a secondary 
outcome.  
 
Primary outcome.   
Weight loss is the 
anticipated 
outcome of the 
intervention.  
Secondary 
 
 
 
Secondary weight outcomes:  
Assess difference between 
study groups in proportion 
losing ≥ 5% body weight 
and differences in mean 
weight loss and proportion 
losing ≥ 5% across 3 pre-
Weight change. 
Weight loss of 5% or more is 
often an objective for weight 
loss studies.  
 

 
 
 
13 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
PUTATIVE 
MECHANISMS OF 
ACTION 
specified subgroups: 1) 
with vs. without diabetes; 
2) females vs. males; and 3) 
Whites vs. African 
Americans. 
 
Secondary Aim 1—
Physiologic and Lifestyle 
Outcomes:  Assess change 
in blood pressure, A1c, 
markers of inflammation, 
skin carotenoids, and self-
reported dietary patterns 
by study group. 
Change in blood 
pressure, A1c, 
markers of 
inflammation, skin 
carotenoids, and 
self-reported 
dietary patterns. 
These are important, relevant 
physiologic and behavioral 
outcomes. 
Weight change in 
response to a 
healthful diet will 
yield clinically 
important 
changes in these 
outcomes.  
Secondary Aim 2—Process 
and Psychosocial Factors:  
Assess process variables 
(attendance, fidelity, and 
acceptability of the Med-
style dietary intervention), 
and key behavioral and 
psychosocial variables, 
including self-
regulation/monitoring 
skills, self-efficacy, 
motivation, and quality of 
life. 
 
Process variables 
(attendance, 
fidelity, and 
acceptability of the 
Med-style dietary 
intervention) and 
key behavioral and 
psychosocial 
variables, including 
self-regulation/ 
monitoring skills, 
self-efficacy, 
motivation, and 
quality of life. 
Process outcomes are 
important for understanding 
how well the intervention was 
given and psychosocial 
variables may provide insights 
on the intervention 
components associated with 
successful outcomes.  These 
variables may be important 
moderators.   
 
Secondary Aim 3--Economic 
Outcomes:  Assess 
implementation cost, and 
incremental cost-
effectiveness of the 
intervention relative to 
control in terms of cost per 
percentage reduction in 
weight (i.e., kg lost) and 
cost per quality adjusted 
life years (QALYs) gained. 
 
Implementation 
costs.  
These data are needed for 
cost-effectiveness analysis.  
 
Tertiary/Exploratory  
 
 
 
Stool Microbiome: Assess 
change in stool microbiome 
Change in 
microbiome 
 
Emerging literature that 
microbiome composition is 
related to dietary intake.  
Microbiome is 
associated with 
dietary intake.  

 
 
 
14 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
PUTATIVE 
MECHANISMS OF 
ACTION 
in response to the 
interventions. 
 
 
4 
STUDY DESIGN 
 
4.1 
OVERALL DESIGN 
This is an open-label, randomized controlled trial enrolling 360 participants desiring weight loss and 
followed over 24 months. Participants will be randomized 1:1, stratified by practice and diabetes status, 
to either: 
• 
Group 1:  Med-South Weight Loss Program (the intervention);  
• 
Group 2:  Weight Watchers (WW™) (augmented usual care) 
Randomized assignment will be done by a computer program stratifying on site and diabetes status and 
using randomly permuted blocks of random sizes for the randomization to achieve balance in the 
participants’ allocation. 
 
--- 
 
From the perspective of NIH, this is a single site study as the intervention is given by one investigational 
team.  That said, participants will be enrolled from several practices in central and eastern North Carolina.  
 
--- 
 
The acronym for the study is DELISH (Delicious Eating for Life in Southern Homes).  The names of the study 
arms are given above.  
 
--- 
 
WWTM was selected as the control group because we think it represents a current standard of care for a 
high intensity intervention that is generally available in both urban areas as well as smaller towns.  
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
Rationale for study design and RCT overview:  We propose an explanatory RCT to assess the efficacy of 
our weight loss intervention. As the type of intervention we propose has not been previously studied in 
a primary care setting (or otherwise) in the US, we believe there is sufficient scientific equipoise to 
undertake an explanatory trial. The primary focus of the intervention will be on dietary behaviors, 
though general information on physical activity will also be given (to the extent we anticipate this will be 
addressed in the augmented control group). Specifically, our focus is to isolate and study the effect of 
the proposed Med-style dietary pattern on weight loss. We propose a sample larger than needed to test 

 
 
 
15 
the primary outcome as it allows us to address secondary weight loss outcomes in 3 pre-specified 
subgroups: 1) those diagnosed with vs. without type 2 diabetes (hereafter, we will use “diabetes” to 
indicate “type 2 diabetes”), 2) female vs. male, and 3) whites vs. African Americans. All of these sub-
groups will comprise at least 40% of the study sample. As we are proposing a behavioral intervention 
trial with the methodological challenges of a non-blinded RCT,76 we will adhere to the updated (2017) 
recommendations outlined in the CONSORT statement for randomized trials of non-pharmacologic 
treatments.76 
3.2c. Control group considerations:  Current evidence suggests “usual care” dietary interventions in 
primary care settings are either absent (only 20% of patients with CVD, diabetes, or dyslipidemia receive 
clinic-based nutrition counseling),77 ineffective,5 or minimally effective (1.2 kg weight loss at 24 
months).3  However, given Task Force recommendations and ethical considerations for patients who 
enroll in a weight loss study, control participants will be offered a weight loss program of an intensity 
consistent with Task Force guidelines (WW™). It will be given free of charge, similar to the experience of 
the intervention group.  Given prior success of weight loss interventions given in primary care settings3, 5 
and by commercial programs,4 we anticipate weight loss at 24 months in our control group will not 
exceed 1.0% of initial body weight.  As noted by Wadden,5 weight loss in the control groups of studies 
conducted in primary care was typically < 0.5%, even among control participants who received 
augmented usual care.78 As we recognize there will be some overlap in dietary pattern between 
intervention and control groups, we propose objective (skin carotenoids) and rigorous self-reported 
measures of dietary intake in both groups to assess the degree of overlap. 
 
4.3 
JUSTIFICATION FOR INTERVENTION 
 
We propose individual counseling for the Med-South Weight Loss Group. Delivery by individual contacts 
(without group-based format as an option) is an adaptation based on: 1) contextual factors (e.g., poor 
patient uptake of group programs, time needed to train and supervise group facilitators, and logistical 
challenges) that could negatively impact group-based delivery in primary care settings,79 and 2) 
advantages of individual contacts and evidence of comparable weight loss outcomes in group vs. 
individual treatment delivery.3, 80  With this change, intervention delivery is made easier for staff in 
primary care settings, provides the advantage of a closer relationship between participant and 
interventionist, and allows tailoring of the intervention to fit the needs of individual participants.  
Participants who receive the WWTM intervention may attend group session (workshops) or use the 
WWTM digital interface for web and/or smart phones.   
 
The number of contacts are similar to what we have used in prior weight loss studies75, 81, 82 and 
consistent with the notion that successful weight loss programs require an intensive intervention.  
4.4 
END-OF-STUDY DEFINITION 
 
The end of study is defined as completing the 24 month follow-up visit.  
 
5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 

 
 
 
16 
 
In order to be eligible to participate in this study, an identified patient must meet all of the following 
criteria. 
 
Step 1—Identify patients from the electronic health record (EHR) who meet the following criteria 
• age 18-75 (inclusive) 
• BMI ≥ 30 kg/m2 
• do not have advanced kidney disease, defined as estimated glomerular filtration rate 30 
mL/min/1.73 m2 as assessed using the MDRD formula) 
• have had a visit at the participating study site within the last 2 years. 
• (effective 10/9/20):  Weight less than 500 pounds. (For the rest of Wave 1 recruitment, we will 
ask potential participants about their weight and exclude if 500 pounds or greater.  Starting with 
data warehouse pulls for Waves 2 and 3, participants will not be eligible if weight is 500 pounds 
or greater) 
 
Step 2—Referred by the patient’s primary care provider (PCP) to take part in this weight loss study.  
Operationally, the study provides a secure link to an Excel file listing the PCPs patient who qualify based 
on EHR review.  
 
5.2 
EXCLUSION CRITERIA 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
Step 1--In thinking about making a referral to the study, we ask the PCP to consider each of the patient’s 
clinical and social context. Please note, a patient should not be referred if any of the following apply: 
• 
Does not speak English 
• 
Too much medical comorbidity (such that a weight loss intervention is not a priority) 
• 
Psychological or psychiatric reasons 
• 
Has type 1 diabetes 
• 
Prior bariatric surgery 
• 
Malignancy other than non-melanoma skin cancer, unless considered cured > 5 years ago. 
Exceptions include 1) men with localized prostate cancer (treated with usual modalities or 
managed with “active surveillance”), and 2) postmenopausal women receiving adjuvant 
endocrine therapy (e.g., aromatase inhibitor) for non-metastatic, hormone receptor-positive 
breast cancer 
• 
Alcohol or substance abuse 
• 
Other reason (please include reason) 
 
 
Step 2—During the eligibility telephone call, we further assess or re-assess the following. 
• Interest:  if not interested, excluded. 
• Is anyone else in the household a participant?  If yes, not eligible. 
• Age: If less than 18 or over 75 at the time of the EHR review, not eligible.  
• “Are you able to make changes to the food you eat? For example, we would not enroll someone 
who lives in a facility where a set menu is served?” If not able to make changes, not eligible. 

 
 
 
17 
• Are you able to access the internet by computer, tablet, or a smartphone on a weekly basis? If 
answer is no, not eligible.  
o (Above updated 11/24/20): Are you able to access the internet by computer, tablet, or 
smartphone on a weekly and, if so, are you comfortable using the internet for email and 
interacting with commercial websites. (By “you,” we mean the potential participant and 
not a family member.  Examples of commercial web sites:  banks, utilities, UNC MyChart, 
etc.) 
• Reassess prior bariatric surgery: If previous bariatric surgery, not eligible.  
• “Do you plan to have bariatric surgery within the next year?” If answer is yes, not eligible. 
• “During the past year, have you taken part in a formal weight loss program through your 
doctor's office or through a private organization like Weight Watchers™ (now WW™) where you 
have attended more than 12 sessions of the program?” If yes, not eligible.  
• “Are you currently taking or in the prior 3 months have you taken prescription weight loss 
medication?”  If yes, not eligible. 
• “[For women, up to age 50] Are you pregnant, breastfeeding, or do you plan to become 
pregnant within the next year?” If yes, not eligible. 
• “Have you had a problem with drug or alcohol misuse within the past 2 years?” If yes, not 
eligible.  A problem is defined as alcohol use that interferes with work activities and/or has had 
a major negative impact on family/social function, the latter defined as more than 2 episodes 
per month.  
• “Have you lost more than 20 pounds in the last 6 months?” If yes, not eligible. 
• Recalculate BMI on self-reported height and weight.  If < 27.5 kg/m2, not eligible.  
• Reassess type 1 diabetes. If yes, not eligible. (If participant not sure, we will check medical 
record and/or contact the primary care clinician.) 
• Reassess cancer risk with algorithm that follows: 
o Have you been diagnosed with cancer other than skin cancer? 
 
 If yes, ask the following. (If no, not excluded.) 
o Have you been told you are cured of this cancer for 5 or more years?  
 
If no, ask the following. (If yes, not excluded.) 
o Are you currently being treated for this cancer with medication or is surgery planned to 
treat this cancer?  
 
If no, continue with the following. (If yes, not excluded.) 
o Let’s assume it is OK for you to take part in this study so let’s complete this survey but I 
will ask one of the study doctors to review your health record to see if you quality. It is 
possible he may want to speak with you by phone. We will be back in touch with you 
about this soon. After physician review, potential participant determined to be eligible.  
 
If yes, potential participant is eligible. If no, participants is excluded. 
•  (effective 10/9/20):  Participant unable to stand on scale unassisted. If yes, not eligible. 
 
Additions to inclusion/exclusion criteria submitted to IRB on 11/16/20 
• 
COVID-19 
o Mild disease:  defined as asymptomatic, mildly symptomatic, or with moderate 
symptoms but not hospitalized.  May start or resume study activities 30 days after 
diagnosis. 
o Severe disease with recovery:  defined as requiring hospitalization, but recovered.  May 
start or resume study activities 90 days after diagnosis or 60 days after hospital 
discharge, whichever comes first.  Additionally, participant needs to convey they are 

 
 
 
18 
mostly recovered (90% or more back to normal).  This will exclude the so called “long 
haulers.”  
o Severe disease with persistent symptoms:  defined as above, but without recovery at 3 
month follow-up.  Do  not enroll and if enrolled, exclude for medical comorbidity.  
 
• 
If a potential participant is referred by their primary care clinician of record on the date of data 
warehouse data review for eligibility, he/she may take part in the study if he/she changes 
primary care clinician, including a clinician outside the UNC system. 
 
Refinement to eligibility protocol.  
• 
After a potential participant completes the eligibility phone call, if deemed eligible, a study 
physician will review the patient’s electronic health record to assess for any change in medical 
status since referral by the primary care clinician that would disqualify the potential participant 
and to confirm that the potential participant meets study inclusion criteria. 
• 
Update 3/4/21—implementation information 
o Physician EHR review for eligibility started with Wave 1, Cycle 4. 
o Starting with Wave 1, Cycle 6 physician also reviewed for diabetes status, but eligibility 
protocol was not updated.  Staff still askes potential participants about diabetes during 
eligibility interview.  
• 
Update 3/4/21—protocol for EHR review 
o Problem list reviewed for 1) diabetes, 2) malignancy, 3) other diagnoses of concern 
including advanced cirrhosis, interstitial lung disease, etc. 
o Medications reviewed for diabetes, medications used for cancer, weight loss 
medication, and overall medical complexity of the patient. 
o “Results Review (lab tab)” reviewed re change in renal status since referral (eGFR < 30), 
diabetes, and for other medical conditions that might preclude participation. 
o Cytology reports for malignancy. 
o Recent progress notes by the PCP reviewed for overall health status of patient and any 
relevant diagnoses that might have been missed as above.  
 
Addendum 11/4/21.  Previously we have allowed HIV positive patients to participate who were 
considered stable and referred by PCP.  This further defines stable.  Stable now defined as RNA below 
the limit of detection and CD4 counts above 400.  
 
5.3 
LIFESTYLE CONSIDERATIONS 
 
During this study, participants are asked to: 
 
• 
Follow the lifestyle recommendations for both dietary change and to be modestly physically 
active. 
• 
If they are unable to make the recommended changes, they will continue in the study.  
Specifically, participants will not be excluded if they fail to achieve lifestyle goals.   
 
5.4 
SCREEN FAILURES 
 

 
 
 
19 
As noted in Sections 5.1 and 5.2, potential participants will be carefully screened for interest and 
eligibility before the enrollment.  We anticipate the number of “screen failures” at the enrollment visit 
will be small and may occur under 2 circumstances. 
• 
If a participant loses weight between the eligibility phone call (when BMI must be greater than 
27.5 kg/m2) such that the BMI at the visit is less than 27.5 kg/m2, the participant is excluded.  
• 
At our UNC internal medicine practice, 97% of patients identified have a creatinine in the EHR, 
which allows us to calculate estimated glomerular filtration rate (eGFR).  Of these 3% have eGFR 
<  30 mL/min/1.73.  We anticipate no more than 400 potential participants will attend the 
enrollment visit (goal enrollment is 360).  Of these, we anticipate about 16 will not have 
creatinine to calculate eGFR.  As a matter of participant safety (we would not want individuals 
with advanced renal disease to take part in the intervention), we will measure creatinine for 
these participants. Of these, we anticipate none will be excluded, but it is possible 1-2 could be 
excluded and this would be after randomization (randomization take places same day as blood 
draw).  
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Framework:  We will recruit individuals within participating practices and will randomize 360 
participants into one of two arms within practices. We will have 2 study locations:  the Chapel Hill 
catchment area and a catchment area in eastern North Carolina.  Participants enrolled in the Chapel Hill 
catchment area (Waves 1 and 2, see below) will have their measurement visits conducted at Center for 
Health Promotion and Disease Prevention, located at 1700 Martin Luther King, Jr. BLVD, Chapel Hill, NC.  
Those randomized to the Med-South Weight Loss Program will have their face-to-face counseling visits 
at this office.  The location for study visits for the eastern North Carolina catchment area is to be 
determined.  
To insure PCPs will be familiar with the majority of patients identified as eligible using the EHR, only 
PCPs who have been at the practice for 10 or more months will be invited to participate.  We will enroll 
participants in 3 sequential waves, with a sample goal of 120 participants for each wave, as outlined 
below: 
 
Wave 1:  Enrollment to start late March or early April, 2020.  Due to a hold on research activities 
related to the Covid-19 pandemic, the first participant was enrolled 6/12/2020.  
o Participating site is UNC Chapel Hill Internal Medicine Practice (academic practice). 
o All PCPs (attendings and residents) who have been at the practice for 10 or more 
months will be invited to review their panel listings of patients who qualify and make 
referrals to the study. 
 
Wave 2:  Community practices in the Chapel Hill area defined as within 25 miles of our research 
office at 1700 Martin Luther King, Jr. BLVD, Chapel Hill, NC. Enrollment to no later than October, 
2020. Originally our plan was to enroll 2 practices.  However, after first contacts with practices, 
we have learned that at some only a sub-set of clinicians might participate.  Realizing some will 
decline, there is no minimum number of participating clinicians required for the practice to 
participate. Depending on the number of PCPs who participate and their panel sizes, we may 

 
 
 
20 
need to recruit from more than 2 practices.  Ultimately, we identified a 3rd practice for Wave 2 
enrollment.   
 
Wave 3:  Eastern North Carolina.  Enrollment to start no later than April 2021.  We anticipate 
working with 2 practices, but it may be more than 2. 
In January 2021, the investigators recognized 1) due to NIH budget cuts and 2) inefficiencies of setting 
up and staffing a second enrollment site, it would not be financially possible to set up a second 
enrollment site in eastern North Carolina.  Thus, for Wave 3, instead of identifying and enrolling 
participants in eastern North Carolina, a decision was made to enroll at 3 additional practices located 
within 25 miles of our study office in Chapel Hill, NC.  
Participants will be randomized within each site. Our primary rationale for randomization of patients 
and not practices is that weight loss interventions (both intervention and augmented usual care) are 
quite intensive and it is unlikely there will be significant contamination between intervention and 
augmented usual care participants (to minimize contamination only one member of a household may 
participate). Also, the intervention is given by research and not clinic staff (which also minimizes 
contamination). Randomization within practices allows for greater statistical power for the sample size 
enrolled. 
Enrollment schedule: 
Participant Enrollment 
  
Grant Year-
Calendar 
year 
Calendar 
Month 
Month of 
Enrollment 
Wave 1 
Wave 2 
Wave 3 
Total  
  
  
  
  
  
  
  
  
1-2020 April  
1   
20   
  
20 
1-2020 May 
2   
20   
  
40 
2-2020 June 
3   
20   
  
60 
2-2020 July 
4   
20   
  
80 
2-2020 August 
5   
20   
  
100 
2-2020 September  
6   
20   
  
120 
2-2020 October 
7   
  
20   
140 
2-2020 November 
8   
  
20   
160 
2-2020 December  
9   
  
20   
180 
2-2021 Jan 
10   
  
20   
200 
2-2021 Feb 
11   
  
20   
220 
2-2021 March 
12   
  
20   
240 
2-2021 April  
13   
  
  
20 
260 
2-2021 May 
14   
  
  
20 
280 
3-2021 June 
15   
  
  
20 
300 
3-2021 July 
16   
  
  
20 
320 
3-2021 August 
17   
  
  
20 
340 

 
 
 
21 
3-2021 September  
18   
  
  
20 
360 
Recruitment and retention of practices:  Study staff will work with the North Carolina Network 
Consortium (NCNC) to identify and enroll study sites.  All community study sites will be UNC Practice 
Network sites that use the UNC Health Care EHR.  Retention of practices is not an issue because all we 
are asking practices to do is have their PCPs make referrals to the study and be willing to review routine 
study lab work (fasting lipid panel and A1c) as this is obtained at baseline and follow-up.  Once a patient 
is referred, study staff will do all measures and will either give the intervention (Med-South Weight Loss 
Program) and refer to WWTM (augmented usual care).   
Recruitment of individual participants:   
Step-1--Identify potential participants from the Data Warehouse (DWH, also called electronic health 
record or EHR).  The DWH is managed by the NC Translational and Clinical Sciences Institute (NC TracDS)  
• 
Potential participants identified as meeting basic inclusion criteria by TraCS programmer using 
DWH (~2,900).  Inclusion criteria are 
o Age 18-75 inclusive 
o BMI 30 or greater at last visit 
o Patient seen at practice during the past 2 years 
o Current PCP has been at practice 10 or more months. 
• 
At UNC Internal Medicine Practice 
o Those who qualify are listed in Excel file (with identified data) made available to study 
staff.  This will be stored in appropriate folder in Study’s OneDrive account. 
o Study staff adds study ID # to the Excel file.  This will be a 6 digit ID (and may increase to 
7 digits if more than 9 sites).  The first digit indicates site.  The next is a separator 0 and 
then 4 digits listing potential participants at the site.  
o Study staff removes patients of study PI (Keyserling) and Co-I (S. Berkowitz) 
• 
At Collaborative Center Coordinating Center (CSCC) 
o Programmer calculates eGFR and those with values less than 30 are removed from the 
dataset 
o Programmer selects a 50% random sample to create file of about ~1500 potential 
participants. 
o For community practices, will likely use entire listing. 
Step-2—Study staff prepares Excel file for each primary care provider (PCPs) 
Step-3—PCPs are sent email with information on how to complete the Excel file listing their patients 
who qualify for the study and a secure unique link to the Excel file (see letter below).  An attachment or 
link to a one page document with more information about the study is also sent.  
The PCP will be asked to refer patients to the study.  In thinking about referrals, the PCP is asked to 
“consider each of your patient’s clinical and social context. Please note, a patient should not be referred 
if any of the following apply:” 
o Does not speak English 
o Too much medical comorbidity (such that a weight loss intervention is not a priority) 

 
 
 
22 
o Psychological or psychiatric reasons 
o Has type 1 diabetes 
o Prior bariatric surgery 
o Malignancy other than non-melanoma skin cancer, unless considered cured > 5 years ago. 
Exceptions include 1) men with localized prostate cancer (treated with usual modalities or 
managed with “active surveillance”) and 2) postmenopausal women receiving adjuvant 
endocrine therapy (e.g., aromatase inhibitor) for non-metastatic, hormone receptor-positive 
breast cancer 
o Alcohol or substance abuse 
o Other reason (please include reason) 
• 
At weekly intervals, we send reminder emails.  A total of 2 reminders will be sent. 
• 
At 2.5 weeks, Dr. Keyserling will try to reach those who have not responded by phone to 
encourage participation.  
---   
Letter to PCP 
We are writing to request assistance in identifying your patients who might qualify for a weight loss research 
study, the DELISH (Delicious Eating for Life in Southern Homes) Study. Although the US Preventive Services Task 
Force “recommends that clinicians offer or refer adults with a body mass index (BMI) of 30 or higher to intensive, 
multicomponent behavioral interventions” for weight loss (Grade B recommendation), there is uncertainty about 
how best to achieve and maintain weight loss. Our research group at the UNC Center for Health Promotion and 
Disease Prevention has received funding from NIH to conduct a randomized trial comparing a new weight loss 
intervention promoting a healthful Mediterranean-style dietary pattern to Weight Watchers (now called WW™).  
Study participants will be randomly assigned to one of these programs (both given free of charge) for a 2-year 
period. (NOTE: The retail value of WW for 2 years is about $1000.) We think patients are likely to benefit from 
study participation and thus hope you will take the time to read the rest of this note and refer your patients to this 
study as appropriate.  If you would like to learn more about the study, click here (add link). 
With IRB approval (UNC IRB# 19-1712) and using the EHR, we have identified your patients who might qualify for 
this study: age 18-75 (inclusive), BMI ≥ 30, do not have advanced kidney disease, and have had a visit at the UNC 
Internal Medicine Clinic within the last 2 years.  Below we provide a secure link to an Excel file listing a 50% 
random sample of these patients. (As we only plan to enroll 120 patients from the ACC practice, we are focusing 
enrollment efforts on a sub-sample of patients.) We ask you to consider referring these patients to the study. 
Patients randomized to the new weight loss program will a receive an intensive weight loss intervention that 
includes multiple counseling sessions with at least 4 sessions delivered in-person and the others in-person or by 
phone. Those randomized to WW will be encouraged to attended WW group sessions and/or use the WW digital 
intervention program.  
In thinking about referrals, consider each of your patients’ clinical and social context. Please note, a patient should 
not be referred if any of the following apply: 
• 
Does not speak English 
• 
Too much medical comorbidity (such that a weight loss intervention is not a priority) 
• 
Psychological or psychiatric reasons 
• 
Has type 1 diabetes 
• 
Prior bariatric surgery 

 
 
 
23 
• 
Malignancy other than non-melanoma skin cancer, unless considered cured > 5 years ago. Exceptions 
include 1) men with localized prostate cancer (treated with usual modalities or managed with “active 
surveillance”), and 2) postmenopausal women receiving adjuvant endocrine therapy (e.g., aromatase 
inhibitor) for non-metastatic, hormone receptor-positive breast cancer 
• 
Alcohol or substance abuse 
• 
Other reason (please include reason) 
Instructions for completing Excel file – As depicted in screenshot below from sample Excel file, for each patient: 
• 
Type a 1 to indicate a yes response in the appropriate yellow, green, or pink cell.   
• 
If you do not refer, please indicate why by typing 1 in the appropriate cell(s) to the right of the pink 
column. It is OK to indicate more than one reason. 
• 
Study staff will call all referred patients to confirm eligibility. 
• 
Study staff will conduct a chart review for patients you don’t know well enough to consider for 
participation and will determine if patient should be invited to take part. 
Below is the link to the Excel file.  Please note: 
• 
After you click on the link, you will receive a passcode to access the file.  If you do not receive it promptly, 
check your junk/spam mail. 
• 
It is fine to scroll:  the patients’ names along with MRNs and column headings are “fixed” and will not 
move with scrolling. 
• 
It takes about 5-10 minutes for every 20 patients listed. 
• 
The Excel file saves all data automatically when entered.  You do not need to save this file—just close 
when done. 
• 
If not able to complete data entry, you can log back in using the same link at a later time/date.    
 [place link here] 
If you have questions, please call or email Kiira Lyons, Project Manager, at 919-843-9563 or 
kiira_lyons@med.unc.edu. 
 
Thank you, 
 
Don't know 
patient well 
enough to 
consider for 
participation 
Refer 
to 
study 
Do not 
refer to 
study 
Does not 
speak 
English  
Too much 
medical 
comorbidity 
Psychological 
or psychiatric 
reasons  
Has type 
1 
diabetes 
Prior 
bariatric 
surgery 
Malignancy, 
active 
treatment or 
not cured 
Alcohol or 
substance 
abuse 
Other 
If 
other, 
specify 
reason 
  
 1 
1 
Moved 
to DC 
1 
  
  
  
 1 

 
 
 
24 
Thomas C. Keyserling, MD, MPH 
Professor of Medicine, Co-Principal Investigator 
 
Carmen Samuel-Hodge, PhD, RD 
Associate Research Professor of Nutrition, Co-Principal Investigator 
--- 
Step 4—Data from PCPs merged back into working Excel data file using the screening ID  
• 
This file will now include a variable for those potential participants who are referred by their 
primary care providers to the study. 
• 
 If the PCP does not know the patient well enough to make a decision about a referral, the 
patient will not be invited to take part in the study. In other words, all study participants will be 
referred by their PCP to the study.  
[Note, 2/26/20:  Step 5 updated to allow enrollment goal of 40% for sub-groups with fewer potential 
participants available for enrollment.] 
Step 5--Identifying potential participants to assess for eligibility with goal of contemporaneous inclusion 
of sub-groups (diabetes status, race and sex). 
• 
We will undertake contemporaneous enrollment within each wave of enrollment for the study 
(Wave 1, UNC Internal Medicine Practice; Wave 2, community practices in Chapel Hill catchment 
area; and Wave 3, community practices in eastern NC). 
• 
 
Selecting participants to assess interest and confirm eligibility:  Our goal is to enroll at least 40% of 
participants with diabetes, African American, and males and our plan is to enroll and achieve this ratio 
contemporaneously, through a series of cycles as outlined below. Our enrollment dataset will include 
participants’ screening ID, diabetes status, sex, and race (from the EHR – we will ask participants to 
report race on our demographic form and this will be the official race variable).  We anticipate that most 
of the potential participants will have been referred to the study by their PCP before we commence 
selecting participants for a Wave.  However, if PCPs who are tardy in referring potential participants to 
the study do so after a cycle, their patients will be added to the pool for the next cycle. 
 
We will invite participants to participate in sequential “cycles” separated by approximately 1 month. We 
anticipate about 1/4 of those invited will participate and our hope is to complete enrollment in four 
sequential cycles, so we will start with a cycle size of 120 for the UNC site (enrollment goal = 120) and 60 
participants for each of the four community practices (enrollment goal per practice = 60). (If it turns out 
our recruitment strategy at community practices focuses more on clinicians than practices, as in 8 
clinicians from 4 practices, we will adjust our numbers accordingly. We will consider this condition to 

 
 
 
25 
represent a virtual practice and will follow this protocol for contemporaneous enrollment of sub-groups 
as if it was one practice.) There are eight possible combinations from crossing the three sub-groups of 
interest (Table 1 below). In the first cycle at the UNC site, the list will include 120 potential participants 
with 12-18 potential participants per subgroup. To align with the pool of applicants, we will initially 
invite a minimum of 40% from each subgroups.  We will select 1) 4 subgroups with the fewest 
participants in each cell or 2) (if subgroups are similar in size), the 4 subgroups with low Ns that includes 
those anticipated to be most difficult to recruit (e.g. males) for 40% enrollment.  This approach should 
allow us to achieve a minimum of 40% in each subgroup.  
 
 
Table 1.  Number of potential participants per sub-group for the first cycle of screening 
  
  
  
  
UNC 
  
Other practices 
Subgroup 
Participant 
with Diabetes 
African 
American 
Female 
N 
% 
  
N 
% 
1 
Yes 
Yes 
Yes 
18 
0.15 
9 
0.15 
2 
Yes 
Yes 
No 
12 
0.10 
6 
0.10 
3 
Yes 
No 
Yes 
18 
0.15 
9 
0.15 
4 
Yes 
No 
No 
12 
0.10 
6 
0.10 
5 
No 
Yes 
Yes 
18 
0.15 
9 
0.15 
6 
No 
Yes 
No 
12 
0.10 
6 
0.10 
7 
No 
No 
Yes 
18 
0.15 
9 
0.15 
8 
No 
No 
No 
12 
0.10 
  
6 
0.10 
Total 
120 
100% 
60 
100% 
 
When recruitment for a cycle is complete, the next cycle of eligible participants will be randomly 
selected from those unselected in the original screening list (i.e. from step 1) with weights for subgroups 
adjusted based on the observed yield of recruitment efforts in the prior cycle(s) using randomization 
procedures in SAS version 9.4.  In other words, if males are under recruited, a greater number of males 
will be included in the next cycle for screening. 
Updated 2/22/21 
Modification for Enrollment for Wave 2 
• 
Plan as discussed and updated at Investigator meeting 9/17/20 
o 
Wave 2:   
 
In working w/ Jennifer Rees, (Practice-based Research Network practice facilitator), 
she had concerns that practices may not agree to participate (based on our early 
outreach before COVID) given all the stressors they are under and may be even 
more stressed with COVID.  
 
So we pivoted to the option of inviting PCPs at practices to participate if they had 
been at the practice for more than 9 months. Our hope is that most will participate. 
We anticipate that we may need to work with clinicians at 3-5 local practices to 
recruit/enroll 120 participants.  That said, the yield may be higher working with 

 
 
 
26 
local practices vs the geographically disperses patient population at the ACC 
practice. 
 
As of 2/22/21: 3 local practices have agreed to participate 
• 
Chapel Hill Internal Medicine (CHIM):   
• 
Weaver Crossing (across the street from our research office) 
• 
Orange Family Medicine 
 
Modification to protocol for Wave 1: 
• 
Recruitment cycles for community practice will include 60 potential participants instead of 120 
as in Wave 1 
• 
As of 2/22/21, Chapel Hill Internal Medicine has referred 329 potential participants with 
breakdown by subgroups as below. Of note, this practice is anticipated to have the lowest 
percentage of Black patients and patients with diabetes. 
o 
11% Black: n= 36 
o 
46% Male: n= 151 
o 
15% Diabetes at least once: n= 50 
• 
Given current high recruitment in Wave 1 of sub-groups of interest (55% African American and 
45% with diabetes), we will set targets as follows for this practice:   
o Blacks: 30% 
o Diabetes: 35% 
o Male 40% 
 
Note on contemporaneous enrollment entered 6/8/25. 
 
V. Contemporaneous enrollment outcomes 
For Wave 1, given the size of the academic practice and our expectation that ½ of the sample might yield 120 
participants, we initiated enrollment by drawing a 50% probability sample (n = 1435) and preparing a referral 
spreadsheet for each PCC from this subsample. We followed our protocol for contemporaneous enrollment of 
subgroups, as described above, and after Cycle 3 (approximately 360 participants invited to participate), we had 
completely depleted patients in 2 subgroups of interests (African American females and males with diabetes). To 
allow for continued enrollment of all sub-groups of interest, we initiated  a second round of enrollment during 
Wave 1 from the remaining sample (n = 1434), excluding 239 patients whose PCC’s were 3rd year residents who 
had graduated from the program.  From this second round of referrals, we prioritized invitations to those in our 
subgroups of interests. 
For Wave 2, which included 2 internal medicine and 1 family medicine practice, the number of patients 
identified from the Data Warehouse ranged from 418 to 534 per practice, with a smaller percentage of patients 
who were African American or patients with diabetes. For these sites, we invited all African American and patients 
with diabetes to participate, as well as most of the white men.  
For Wave 3, which included 2 family medicine practices and 1 internal medicine/pediatrics, the number of 
patients identified from the EHR ranged from 234 to 351.  During Wave 3, the study met is quota for white females 
without diabetes. Accordingly, the names of 151 white females with diabetes were not included on referral 
spreadsheets distributed to Wave 3 PCCs; all identified as African American, patients with diabetes, and male were 
included on these spreadsheets.  

 
 
 
27 
 
Step 6—Contacting participants identified in Step 5 to assess eligibility and interest  
Mail information brochure and cover letter to potential participants identified as outlined above and 
request that within one week, those who 1) know they are interested or 2) know that they are NOT 
interested send us an email or call to provide this information. Place those who express interest on our 
call list.   
• 
Approximately 10 days after mailing, start calling those who we do not hear from.  Our call 
protocol is as follows: 
o We will call up to 5 times over a 2 week period. We will attempt 2 calls during regular 
work hours (8:30 to 5:30 on weekdays) and 3 after hours, including Mon-Thurs evening 
between 5:31 and 9:00 pm and on Saturday calling between 8:30am and 5:30 pm.  
o We will leave up to 2 phone messages. 
• 
During eligibly calls, data are entered into the REDCap eligibility questionnaire. This form also 
has fields for tracking information on attempted calls for the phone call.  
• 
If a potential participant is interested and eligible, staff will either mail or email the consent 
forms to this individual and an appointment will be made for the consent phone call in about 1 
week.  
 
Step 7—Study staff updates the Excel data base based on eligibility phone call.  
• 
Status variable 
o 1 indicates potential participant agrees to be contacted again for Consent Phone call.  
o 2 indicates potential participant contacted, but not interested.  Identifying data is 
removed. (Name, DOB, address, and phone #). 
o 3 indicates potential participant contacted and is interested, but not eligible.  Identifying 
data is removed. (Name, DOB, address, and phone #). 
o 4 indicates potential participant never contacted by phone. Identifying data is removed. 
(Name, DOB, address, and phone #). 
Step 8—Consent phone call  
• 
At this phone call, key components of the consent form are reviewed in detail to insure that the 
potential participant understands what participation entails.  During the phone call, the “Stored 
Specimens with Identifiers” and “HIPAA Authorization” are also reviewed. It the potential 
participant agrees to sign consent form via e-consent, instructions are given on how to do so. If 
the potential participant prefers to sign at the enrollment visit, then verbal consent to complete 
baseline questionnaires before the enrollment visit will be obtained, as approved by the IRB.   
• 
Instructions for completing baseline forms, on-line or by phone, are given and plans to complete 
these forms are made accordingly.  An appointment date is set for the baseline visit.  
• 
Parameters for contacting the patient are the same as for the eligibility phone call outlined in 
Step 6.  
  

 
 
 
28 
Enrollment visit and randomization: At the enrollment visit, all questions will be answered about the 
study and those who did not sign the consent forms on-line (e-consent) will sign the consent form. Upon 
completion of baseline measures (except for the stool sample) the participant will be ready for 
randomization. The research assistant will use the randomization function in REDCap to ascertain 
randomization assignment. 
 
Insuring enrollment of “vulnerable populations”:  We will purposefully recruit vulnerable populations 
(low-income and minority patients) primarily through our selection of study sites that serve a large 
population of vulnerable patients and also recognizing that these populations are overly represented 
among those with obesity and diabetes. 
Retention of individual participants:  To enhance retention of participants, at enrollment, we will ask 
for home and cell numbers, if it is OK to send text messages, and if it is OK to contact by email and/or 
the web communication function of the EHR (at UNC, this is called MyChart). We will also ask 
participants to provide contact information for an alternate contact (friend or family member) in case 
we are unable to reach them directly. In attempting to schedule a follow-up contact, we will allow up to 
5 attempts to reach a participant over a 2-week period and up to 3 attempts to reach the alternative 
contact. Our goal is to contact participants who are late for study activities early and often in support of 
their participation. Though we will promote participation in a timely fashion as much as possible, we will 
also respect study participant’s desire to withdraw from the study at any time.  
Incentive for participation:  Their weight loss interventions (both Med-South Weight Loss Program and 
WW™) are given for free.  Measurement visit at baseline and 4, 12, and 24 months are compensated at 
the rate of $60, about $20-30 per hour.  Travel for measurement visit greater than 20 miles is 
compensated at the state of NC compensation rate. We do not think this compensation is coercive and 
think the rate is in line with what the IRB typically endorses for measurement visits. To enhance follow-
up at 24 months, compensation was increased to $100.  
Possible competition from other trials, secular trends, and co-interventions: We do not anticipate 
major competition from other weight loss trials. However, if others are funded, as outlined above, we 
believe there are ample numbers of patients with obesity for our trial and others. It is unlikely that 
secular trends will have a major impact on weight change, but if they do, they should have similar 
impacts across our two study arms. Similarly, co-interventions such as diabetes medications that are 
associated with weight loss would likely be equally distributed across study arms. If not, we could 
control for this factor in the analysis as we are assessing specific types of medications for diabetes. 
Finally, participating sites may begin to routinely offer more effective weight loss programs. However, all 
our participants should be taking part in our study weight loss interventions, so it is unlikely that such 
programs would have a major impact on study participants. 
 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION DESCRIPTION 

 
 
 
29 
 
As depicted by the study flow diagram (Section 1.2), the experimental intervention (Med- 
South Weight Loss Program) is given in 3 phases.  In this section, we will outline the overall features of 
the intervention and modifications we plan to make to the previously tested intervention.  However, 
only a detailed description of Phase I will be provided in this version of the protocol.   That is because, as 
planned, we are still revising the Phase II and III interventions to be up-to-date and consistent with the 
literature.  Phase II begins in July, 2020. 
 
The enhanced usual care intervention (control arm of the RCT) will be WW™, both workshop and digital, 
for 2 years.  We will encourage patients in this arm at the outset of the study.  Once the information is 
given about stating WW™ and we are confident the participant knows how to access this program, we 
will not actively promote their participation in the program (our goal is to approximate what might 
happen if a PCP refers a patient to WW™).  As noted above, at measurement visits we will assess 
participation in WW™ and through a data use agreement, WW™ will provide us with process data.  
Information about WW™ can be accessed at the program’s web site: 
https://www.weightwatchers.com/us/. 
 
Description of the Med-South Weight Loss Program (note the text below is take from our research 
proposal and the proposal sub-headings have been maintained.) 
 
3.3. Description of the intervention—the Med-South Weight Loss Program  
Conceptual Model:  The intervention conceptual model (see Fig.) combines constructs from cognitive 
and behavioral change theories. Our behavioral approaches are derived primarily from social cognitive 
theory (SCT),83, 84 targeting self-efficacy, motivation, and self-regulation skills which have been identified 
as the best 
predictors of 
positive weight 
and physical 
activity 
outcomes.85-87 To 
effect these 
predictors, the 
weight loss 
intervention, 
similar to other evidence-based programs,88-92 incorporates techniques such as motivational 
counseling,93 problem-solving,94 self-monitoring, goal-setting, and cognitive (acceptance and 
commitment) strategies to address challenges to self-regulation of diet and physical activity.95 In 
addition, food-related and socioeconomic barriers to lifestyle behavior changes will be assessed and 
addressed in intervention content. At the patient level, our model also recognizes the importance of 
dietary pattern as a key contributor to long-term intervention success. In the Women’s Health Initiative 
RCT, most participants could not achieve and maintain the very low-fat diet that was recommended.17  
However, in the PREDIMED RCT, the higher fat, Med-style diets were maintained by study participants 
for the duration of the RCT.96   
 
Overview: The Heart Healthy Lenoir weight loss intervention described below in ital. will be refined for 
this study.75  The intervention is given in 3 phases as outlined in Fig 2. Below, we first outline 
intervention adaptations to enhance weight loss by phase and then across phases. In Sec. 3.4d we 

 
 
 
30 
describe enhancements for intervention implementation, which are relevant to future dissemination if 
the intervention is shown to be effective.  
--- 
3.1b. Preliminary data directly related to this application--Heart Healthy Lenoir (HHL) lifestyle and 
weight loss study: This study (Keyserling, PI)74, 97 integrated weight loss components from the studies 
described above with a previously tested lifestyle intervention98, 99 to create the intervention that will be 
refined and tested 
in this proposed 
study. With 
funding from 
NHLBI as part of 
the Centers for 
Population Health 
and Health 
Disparities 
(Ammerman, 
overall PI),100 this 
study enrolled 339 
participants. All 
received an initial 
4 month lifestyle 
intervention 
(Phase I), after 
which, those with 
a BMI > 25 kg/m2 
desiring weight 
loss (N = 138) 
enrolled in the 
weight loss intervention (Phase II) offered in 2 formats: 16 weekly group sessions (n = 57) or combination 
of 5 group sessions and 10 phone calls (n = 81). From 12 to 24 months (Phase III), both weight loss 
groups received a telephone-administered maintenance intervention. After Phase I, those who did not 
take part in the weight loss intervention continued with the lifestyle intervention which consisted of 
phone follow-up every 3-4 months. The dietary pattern advocated across all phases was very similar to 
the nut intervention arm tested in the PREDIMED RCT,21 hence, we call it the Med-South diet. 
(Educational materials included in supplement to major outcomes paper.74) The PREDIMED intervention 
diets21 included 13 major recommendations. In Table 1 (see page above), we list these and show that 9 of 
the 13 are virtually identical to those tested in the Med-South diet in HHL. Importantly, we adapted the 
Med-South diet to include foods familiar to and affordable for residents of the Southeast (and more 
generally, the US), such as peanuts and peanut butter (same heart health quality as tree nuts101) as part 
of the recommendation to eat nuts ≥ 3 times a week and full-fat salad dressing as familiar foods with 
high-quality fats. Further, our adapted recipes for traditional southern foods, such as BBQ102 and hush 
puppies,102 were well-received by participants.  
We have recently reported weight loss outcomes (Table 2) through 24 months for those with diabetes 
(n=124) who took part in HHL.75 (As noted in Sec. 3.3d, we expect greater weight loss in this study.) 
 

 
 
 
31 
Table 2:  Weight and change in weight (% change) at 12 and 24 month follow-up for HHL Participants with Diabetes 
 
12 Month Weight Outcomes 
24 Month Outcomes 
Intervention Format 
N 
Baseline Wt. 
% Change (95% CI) 
N 
Baseline Wt. 
% Change (95% CI) 
--with diabetes, group weight loss 
17 
108 
-3.6 (-6.9 to -0.4) 
18 
109 
-4.8 (-8.8 to -0.7) 
--with diabetes, combo weight loss 
27 
110 
-2.6 (-5.0 to -0.2) 
25 
108 
-2.0 (-4.3 to 0.1) 
--with diabetes, lifestyle only 
52 
100 
-0.2 (-2.0 to 1.6) 
50 
101 
-3.8 (-5.9 to -1.8) 
 
Overall, among participants with diabetes, the mean percent weight change at 24 months was -3.6% (-
5.0 to -2.0). In addition, 33% of participants with diabetes maintained 5% weight loss and 20% 
maintained 7.5% weight loss at 24 months. Ninety percent of those in the weight loss program were 
satisfied or very satisfied with the program. Importantly, among those in the lifestyle only group, weight 
loss was -3.8 kg (-5.9 to -1.8) at 24 months, suggesting a change in dietary pattern may have led to 
weight loss75 without an explicit intervention to lose weight. A possible explanation for weight loss in this 
group, as compared to PREDIMED participants who on average lost minimal weight,48 is difference in 
baseline diet, with more poor quality carbohydrates and processed food in the American diet compared 
to the European diet 103 and particularly so in the southeastern United States.104-107 In this setting of 
excess poor quality carbohydrate intake, a change to a Med-style, unrestricted high-quality fat diet may 
have positive metabolic and appetite suppressing effects.62, 63, 65  A major limitation of HHL weight loss 
outcomes was the pre-post study design, though weight loss over time is not commonly observed for 
adults and there were no secular trends suggesting weight loss in NC during the time of this study.108 
Also, the weight loss trajectory among participants with diabetes in HHL was different from most weight 
loss studies—weight loss improved over time, instead of the usual rapid weight loss over 6 months with 
attenuation of weight loss typically seen at 12 and 24 months.109  This trajectory of weight loss may be 
clinically important in light of increased CVD risk reported for those with weight fluctuations.110 
 
Among participants without diabetes in HHL, weight loss was 0.4 kg (-1.4, 0.6) at 24 months. There are 
several reasons why those without diabetes may have had less weight loss. On average, they weighed 8 
kg (103 vs. 95) less at baseline75 and the majority (54%) did not choose to be in the weight loss 
intervention. Thus, they may have had a lower level of motivation to lose weight than those with 
diabetes. Furthermore, both short- and long-term weight loss has been shown to be greater when the 
trigger for weight loss is medical in nature.111 
 
3.3a. Phase I (4 months), lifestyle phase:   
Behavioral content enhancements: We will enhance the initial 4 month lifestyle phase with additional 
content that focuses on preparing participants for the weight loss intervention in Phase II by introducing 
a set of stability skills shown to improve long-term weight management.112  Proposed stability skills 
enhancements include: 1) learning how to eat healthfully without feeling deprived or dissatisfied; 2) 
becoming comfortable with frequent self-weighing (making peace with the scale); and 3) navigating 
inevitable disruptions.112 However, there is still no expectation for weight loss during this phase.   
 
Dietary composition enhancements/rationale: The tested Med-South program recommended frequent 
consumption of vegetable oils (including olive oil, but not specifically recommending olive oil) and nuts, 
including peanuts.113 Given the benefits of extra virgin olive oil as demonstrated in PREDIMED,21 we will 
encourage consumption of extra virgin olive oil for those who like the taste and can afford it. However, 
the intervention will continue to recommend consumption of low cost and familiar oils such as soybean, 

 
 
 
32 
peanut, and canola oil, as the scientific data supporting the positive health effects of vegetable oils with 
high polyunsaturated fatty acids (PUFAs) content are compelling,114-116 including a beneficial effect of 
omega 6 PUFAs on CVD and total mortality.38  Our rationale for recommending fish ≥ 1 serving per week 
vs. ≥3 servings is 1) cost-related, as fish can be expensive, and 2) scientific, as most of the benefit from 
fish consumption is realized with 1 serving per week.117  PREDIMED limited spread fats to < 1 serving per 
week, but now that non trans-fat tub margarines are available with high-quality fat content (e.g., Smart 
Balance™ and others), we recommend consumption of high-quality spreads. As sofrito sauce is not 
commonly consumed in the US, we are not recommending it, but instead, familiar foods made with 
tomatoes, onions, and garlic such as salsa. 
 
Of note, the proposed modified Med-South dietary recommendations are consistent with 1) the 
recently updated guidelines (2018)118 from the American Diabetes Association, which recognize the 
merits of a Med-style dietary pattern, and 2) USDA Dietary Guidelines 2015-2020.119 Given 
commercialization of the American food environment (chain restaurants/processed foods), food 
consumption patterns are similar across the country; thus, the Med-South dietary approach is likely an 
appropriate intervention for most of the US. 
 
3.3b. Phase II (next 8 months), weight loss:  The proposed behavioral weight loss intervention builds on 
the HHL weight loss program (Sec. 3.1b, see above).    
 
Weight loss enhancements: To improve short- and long-term outcomes, recent research supports the 
integration of additional cognitive components into the cognitive-behavioral treatment of obesity.95, 120-
122  These cognitive approaches, which include skills in mindful eating, acceptance of cravings and 
behavioral fatigue, behavioral commitment to clearly-defined values, and increasing awareness of how 
internal and external cues motivate eating decisions,95, 120-122 will be incorporated into the content of the 
weight loss intervention. In addition, 3 key modifications are proposed to enhance the implementation 
of an adapted-HHL intervention delivered in a primary care setting. These modifications include: 1) an 
extended weight loss period (increased from 6 to 8 months); 2) individual contacts only (in-person and 
by phone); and 3) early identification of non-responders with optional stepped up care. The extended 
weight loss period of 8 months (2 months longer than standard 6-month treatment duration) is largely 
based on the desire to allow more time for weight loss and a 12-month measurement interval from 
baseline. With this longer weight loss period, participants may also benefit from additional intervention 
contacts. Delivery by individual contacts (without group-based format as an option) is an adaptation 
based on: 1) contextual factors (e.g., poor patient uptake of group programs, time needed to train and 
supervise group facilitators, and logistical challenges) that could negatively impact group-based delivery 
in primary care settings,79 and 2) advantages of individual contacts and evidence of comparable weight 
loss outcomes in group vs. individual treatment delivery.3, 80  With this change, intervention delivery is 
made easier for staff in primary care settings, provides the advantage of a closer relationship between 
participant and interventionist, and allows tailoring of the intervention to fit the needs of individual 
participants. New research123, 124 guides our decision to identify non-responders early and then adapting 
the intervention to fit the needs of the individual. With this modification, we can step-up care for those 
participants who need additional contacts while maintaining the standard treatment for “responders.”  
 
3.3c. Phase III (next 12 months), long-term weight loss and maintenance of weights loss:  The 12 
month (Phase III) follow-up period provides an opportunity to determine weight loss maintenance 
success and weight change after the initial weight loss period. Weight loss maintenance following 
intentional weight loss remains challenging125-127 mainly due to poor adherence to behavioral strategies 
and “physiological adaptations that promote weight regain.”128  Extending treatment following intense 

 
 
 
33 
weight loss programs can produce maintenance of an additional 3.2 kg of weight loss over 18 months, 
compared with no-treatment controls.125  
 
Weight loss enhancements: We will build on strategies proven effective in our own studies and in other 
published research, while being cognizant of primary care setting contextual factors. Based on a review 
of the current evidence, extended care using personal contacts showed greater effectiveness in weight 
loss maintenance than technology-based interventions.129 Some of the more effective weight loss 
maintenance interventions130-132 have used phone counseling,133, 134 and/or in-person contacts, generally 
delivered on a monthly basis. Our program includes monthly phone contacts with the option of biweekly 
contacts depending on individuals’ progress. Adapting the number of contacts to match individual 
responsiveness is an important modification that addresses individual variability as a behavioral 
challenge to weight loss maintenance.  
 
3.3d. Intervention enhancements across all phases 
Dietary composition: In recognition that dietary composition impacts energy expenditure during weight 
loss maintenance (Sec. 1.2d) with low-glycemic and low-carbohydrate dietary patterns associated with 
improved maintenance of weight loss,63,64 we will update our materials on carbohydrate 
recommendations to emphasize even more the importance of 1) regularly consuming lower glycemic 
fruits, less starchy vegetables, and whole grains and 2) reduced intake of their starchy/refined 
counterparts. 
 
With these enhancements, we anticipate mean weight loss of ≥ 5% body weight at 24 month follow-up. 
 
3.3e. Physical activity (PA) component. In HHL, we devoted about 25% of counseling time to an 
individually tailored, goal-oriented PA intervention advocating increased moderate intensity PA and 
decreased sitting time.74 For this proposed explanatory trial with a primary focuses on dietary pattern 
and weight loss, we do not propose a high intensity PA intervention component. Instead, we will 
periodically mention PA recommendations consistent with national guidelines,135 but no structured 
counseling is planned for PA behaviors. We anticipate PA will be roughly the same in intervention arms; 
however, we will carefully measure self-reported PA so we can control in our analysis for observed 
differences between groups, if present. We will ask participants to report their physical activity, 
particularly walking. We will assist participants in tracking their steps with use of a smart phone and will 
provide a pedometer to those without a smart phone for this purpose. 
 
6.1.2 ADMINISTRATION AND/OR DOSING 
 
Logistics of giving the Med-South Weight Loss Program 
• 
The intervention will be given by trained research staff.  
• 
For participants recruited from the Chapel Hill catchment area, the intervention will be 
delivered in person and by phone: 
o In person, face-to-face counseling visits, will be given at the UNC Center for Health 
Promotion and Disease Prevention, located at 1700 Martin Luther King, Jr BLVD, Chapel 
Hill, NC 27599. A minimum of 4 in-person counseling visits will be delivered at this 
location (first visit of Phase I, first visit of Phase II, 2 month follow-up visit of Phase II, 
and first visit of Phase III).  
o The other visits may be given in person or by phone.  The phone counseling sessions 
may be supplemented with use of shared screen technology (e.g., Zoom™ session) 

 
 
 
34 
• 
The location of our counseling sessions in Eastern North Carolina is to be determined and will 
included in a further version of the protocol.  (Enrollment visits in eastern North Carolina will 
start no later than April, 2021.) 
• 
We will encourage participants to take part in all sessions.  However, a participant will not be 
dropped from the study based on session participation.  In the extreme, we will invite 
participants back for measurement visit even if they did not participate in any intervention 
counseling sessions.  
• 
If a participant takes part in 70% or more of anticipated visits, we will consider this a “full-dose.”   
• 
The intervention format for this study is individual; there will be no group sessions or activities.  
 
Description of Intervention for Phase 1 
Phase I – Lifestyle Intervention:  The content for this phase is currently available at:  
http://hpdp.unc.edu/research/medsouth/med-south-materials/.  As outlined below under Phase I 
modifications, we will adapt the current physical activity intervention so that 1) it is less intensive than 
previously tested by our group and 2) approximates what we anticipate to be the physical activity 
recommendations in the augmented control group.  Our goal in doing so is to isolate the dietary pattern 
as the primary behavioral intervention evaluated in this study. 
Session Content and Delivery: The following content is addressed during the 4 major counseling session: 
• 
Session 1:  Nuts, Dressings, and Oils 
• 
Session 2:  Vegetables, Fruit, Whole Grains, and Beans.  
• 
Session 3:  Drinks, Desserts, Snacks, Eating Out, and Salt 
• 
Session 4:  Fish, Meat, Poultry, Dairy, and Eggs 
At the first session, an overview of the program is given, an assessment of dietary behaviors relevant to 
session content is administered, and then the specific dietary content for Session 1 is presented.  At the 
end of the session, the participant and counselor developed an individually tailored action plan to help 
guide the participant’s eating behaviors for the next month (or until the next counseling session).  To do 
so, they first review the assessment page for Session 1 and identify current eating behaviors that “could 
be improved” (middle column) or “need to be improved” (right most column) of assessment page. (In 
the Web-based version, problematic eating behaviors are presented according to an algorithm that 
prioritizes behaviors most in need of modification to improve CVD risk and counseling is organized as 
described for the paper version in this section.)  Then they review the dietary tips for these problematic 
eating behaviors on the tip sheet for Section 1 with tips linked by number and color coding to the items 
on the assessment page.  Of note, the tip sheet includes recipe suggestions in a "Southern Style" 
cookbook given to all participants.   Finally, the counselor and participant identify 2 achievable goals 
(participants can opt to choose 1) to work on before the next visit and document them on the goal 
sheet.  Subsequent sessions follow the same format but open with a check-in on progress toward goals 
and address diet and physical activity.   
Approximately 1 week after the counseling sessions outline above, there is a follow-up phone call.  
During this phone call, the counselor will check on goals and 1) offer reinforcement for success in 
achieving goals or 2) problem solved issues related to lack of success in achieving goals.  If the latter is 

 
 
 
35 
the case, the counselor and participants may collaboratively selected new goals to focus on before the 
next session. We anticipate these phone calls will last 10-15 minutes. 
Phase I Enhancements/Modifications: In addition to the behavioral components already integrated into 
the lifestyle intervention, we propose to add a small set of cognitive skills that have been shown to 
improve weight loss maintenance, even without continued program contacts.112 These skills increase 
intrinsic motivation to engage in lifestyle and self-regulation behaviors. Some of these ‘stability skills’ 
were included in our prior weight loss research, but not in the initial lifestyle phase. The table below 
(based on the Kiernan study112) includes a brief summary of 4 stability skills and examples of 
activities/discussions that will be integrated into the 4 monthly sessions. 
 
Stability Skills 
Skill-Building Activities / Discussions 
□ Learning how to eat 
healthfully without feeling 
deprived or dissatisfied 
o Reduce comparisons between ‘healthy vs. less healthy foods’ (to lower 
perceived deprivation) 
o Find tasty replacements for foods that should be limited in frequency and 
quantity 
□  Becoming comfortable with 
frequent self-weighing 
(making peace with the scale) 
o Weigh daily, track weight, and observe fluctuations to identify personal 
range 
o Practice interpreting weight fluctuations (gains) with calm, relaxed 
awareness and fine-tuning/adjustments 
□  Making quick and easy 
adjustments to stabilize 
weight 
o Making small adjustments without keeping food/activity records 
o Eating (savoring and enjoying food) mindfully 
□  Navigating inevitable 
disruptions 
o Recognize that disruptions are to be expected 
o Practice navigating high-calorie meals (e.g., Sunday family gatherings, 
vacations) 
Other Cognitive and Behavioral Skills (based on principles and techniques of Cognitive Behavioral and Acceptance 
Commitment Therapy) 
□ Cognitive Behavioral Skills: Motivation, Self-Compassion, Distorted Thinking, Cognitive Restructuring, Positive 
Thinking, Emotional and Situational Triggers, Problem-solving, etc. 
□ Acceptance-Based Skills: Commitment to Behavior Change, Distress-Tolerance Skills, Mindful Awareness (eating 
behaviors) 
 
For this proposed explanatory trial with a primary focuses on dietary pattern and weight loss, we do not 
propose a high intensity physical activity intervention component. Instead, we will periodically mention 
physical activity recommendations consistent with national guidelines, but no structured counseling is 
planned for PA behaviors. 
 
Phase II – Behavioral Weight Loss Intervention: 
 

 
 
 
36 
PHASE II WEIGHT LOSS PROGRAM (8 MONTHS) 
 
 
 
 
Overview:  The weight loss program for this study builds on our previously successful weight loss programs,[1-5] 
especially the Heart Healthy Lenoir Project.[3, 5]  Refinements for this program include:  
o 
Dietary factors:  Research into macronutrient composition of meals, meal timing, and satiety and fullness, and 
partial use of portion-controlled meals are among the dietary factors we incorporate into the intervention for 
personalizing the approach to weight loss and especially for early non-responders 
o 
Cognitive and Behavioral strategies:  Principles of cognitive behavioral therapy (CBT), acceptance commitment 
therapy (ACT), and mindfulness are integrated into the refined program content. 
Planned sessions as outlined in consent form:   
 
Phase II 
• 14 core sessions: the first and 
a visit about 2 months later 
must be in-person; choice of 
in-person or phone for all 
others. 
• 6-12 follow-up phone calls  
• Core session (in-
person) = 45-60 min. 
• Core session (phone) = 
30-45 min. 
• Follow-up call = 20-30 
min. 
 
8.7 – 14 hours 
(core) 
 
4.7 – 9.5 hours 
(Follow-up) 
 
More detail on sessions and adaptive approach.  As outlined in the table below: 
• 
The first 8 core sessions are given weekly with the first in-person. 
• 
The next 6 core sessions are given monthly, with 1-2 shorter follow-up phone calls given between 
sessions. 
• 
Adaptive approach: Non-responders will be identified at 2 months and the intervention adapted to 
address the factors contributing to non-response.  Limit to number of contacts in last 6 months is 
maximum of 2 monthly phone follow-up contacts added to the core monthly session. 
• 
Note: Phase II Weight Loss Program content (sequence in which content is covered) may be adapted to 
meet the needs of individual participants.  Each session includes conversations specific to dietary 
behaviors, the Med-South eating pattern, and weight loss progress 
 
Session 
Core Session Content  
Week 1*  
In-person visit required (4M Data Collection visit). 
 Review of weight loss phase and study weight loss goal**  
 Self-monitoring strategies (focus on self-weighing and food intake) 
 Estimated energy needs + caloric restriction for modest weight loss 
 Weight loss and diabetes and high blood pressure (safety recommendations 
for those on medication for diabetes and/or blood pressure) 
 PA recommendations for weight loss 
 
Week 2 
 Med-South weight loss – personal meal planning (macronutrient composition 
match to adherence; timing of meals, etc.) 
 Values, commitment, and behaviors  
 Planning, food purchasing and meal prep 

 
 
 
37 
 
Week 3 
 Social support communication 
 Food, fullness, and satiety 
 Revisit Breakfast meal 
 Additional resource: whole grains and fiber (Manual pg. 25) 
 
Week 4 
 Stress management 
 Emotional Eating 
 Revisit Lunch meal 
 Additional resource: meal prepping (Manual pg. 76) 
 
Week 5 
 Personal Feedback Report 
 Managing thoughts  
 Revisit Dinner meal 
 
Week 6 
 Time management and values 
 Revisit Snacks 
 Mindful eating – Part 1 
 Additional resources: Desserts, sweets, and snacks (Manual pg. 42), Kitchen 
Tips and Tricks (Manual pg. 75) 
 
Week 7 
 Control and acceptance 
 Problem-solving skills 
 
Week 8 
 Eating out, Special occasions 
 Hunger cues 
 Additional resource: Eating out and strategies (Manual pg. 44) 
 
Monthly contacts with 1 - 2 follow-up phone contacts (Months 3-8) 
Session 9*  
+ f/u contact  
In-person visit (required for non-responders) 
 Personal feedback report 
 Adapted weight loss approach based on personal factors (dietary and 
behavioral) 
 Eating pattern review and adjustments (meal timing, size, etc.) 
 
Session 10 
+ f/u contact 
 Mindfulness -Part 2 
 Overeating triggers 
Session 11 
+ f/u contact 
 Revisit self-monitoring 
 Distorted thinking 
Session 12 
+ f/u contact 
 Personal feedback report (6M) 
 Adaptations to weight loss approach based on personal factors 
 Revisit Motivation 
 
Session 13 
+ f/u contact 
 Rewards and Affirmations 
 Relapse prevention 
 Weight loss maintenance 
 

 
 
 
38 
Session 14 
+ f/u contact 
 Support for weight loss maintenance 
 Study WLM goals (review) 
 Visioning 24 months out 
 
*In-person visit required 
**To-achieve a 5% weight loss at 24 months, we need to account for at least a 1-3% weight regain. 
Thus our aim is for about 7% weight loss goal by 12 months (end of Phase 11 weight loss program). 
 
REFERENCES 
 
1. 
Samuel-Hodge, C.D., et al., A pilot study comparing two weight loss maintenance interventions among 
low-income, mid-life women. BMC Public Health, 2013. 13: p. 653. 
2. 
Samuel-Hodge, C.D., et al., Translation of a behavioral weight loss intervention for mid-life, low-income 
women in local health departments. Obesity (Silver Spring), 2013. 21(9): p. 1764-73. 
3. 
Keyserling, T.C., et al., A community-based lifestyle and weight loss intervention promoting a 
Mediterranean-style diet pattern evaluated in the stroke belt of North Carolina: the Heart Healthy Lenoir 
Project. BMC Public Health, 2016. 16: p. 732. 
4. 
Samuel-Hodge, C.D., et al., Family PArtners in Lifestyle Support (PALS): Family-based weight loss for 
African American adults with type 2 diabetes. Obesity (Silver Spring), 2017. 25(1): p. 45-55. 
5. 
Embree, G.G., et al., Successful long-term weight loss among participants with diabetes receiving an 
intervention promoting an adapted Mediterranean-style dietary pattern: the Heart Healthy Lenoir Project. 
BMJ Open Diabetes Res Care, 2017. 5(1): p. e000339. 
 
 
 
Phase III – Continued Weight Loss and Maintenance of Weight Loss:: 
 
Phase 3 of DELISH counseling (Maintenance) prioritized three in-person visits (start of year 2, the 18-month 
halfway point, and the final visit at the 24-month end point) to educate the participants on weight-loss 
maintenance and how to continue with their goals once the intervention ended. In between these in-person 
counseling and measurement sessions, counselors provided monthly counseling sessions via phone as needed for 
each participant. Additional in-between phone call check-ins were available if requested by the participant. These 
sessions, both monthly and in-between calls, were more flexible and allowed the participants to choose which 
materials and educational handouts they wanted to focus on before finishing the intervention. This individualized 
counseling approach allowed for specialization of each participant’s interests and needs as they finished up the 
intervention.  
 
 
6.2 
FIDELITY 
 

 
 
 
39 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
 
We will assess fidelity in intervention delivery as follows: 
• 
Enhanced usual care (WW™):   
o 
Per our data use agreement, WW™ has agreed to provide the study with the following 
process data:  number of workshops attended (including dates of visits), workshop 
weights (if available), number of website or phone app logins (including dates and 
duration if available), and participant reported dietary and physical activity data.  
o At all study follow-up measurement visits (4, 12, and 24 months), research staff will 
carefully assess number, type, and duration of weight loss counseling sessions complete 
as part of the WW™ program. 
• 
Med-South Weight Loss Program:  We will assess fidelity of intervention delivery through 
multiple channels as describe below. 
o All counseling sessions will be logged into our REDCap data management program, 
including date and duration of visit.  
o After each visit, the counselor completes a checklist to indicate the components of 
counseling that were covered during the visit. 
o Audio recordings of up to 20% of sessions will be conducted during the 2-year period.   
 
During Phase I and the early part of Phase II (first 2 months) a random 50% of 
the recorded counseling sessions will be reviewed and feedback provided to 
counselors.  Recordings will be reviewed by study staff using a checklist to 
assess planned counseling components (accuracy of content covered and 
quality of delivery). If we find delivery fidelity is less than 80% of anticipated 
based on successful completion of counseling components, then the frequency 
of providing feedback to counselors from reviewed audio recordings will 
increase to ensure that the delivery fidelity goal has been achieved.  
 
During the latter part of Phase II (last 6 months) and Phase III, audio recording 
will drop to 10% of visits (with review of up to 50% of recorded sessions), unless 
delivery fidelity is not achieved, in which the proportion reviewed will be 
increased to document achievement of fidelity goals. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
Randomization 
This is an open-label, randomized controlled trial of 360 participants desiring weight loss and followed 
over 24 months. Participants will be randomized 1:1, stratified by practice and diabetes status, to either: 
• 
Group 1: Med-South Weight Loss Program (the intervention);  
• 
Group 2: WW™ (Augmented usual care).  
Randomized assignment will be done by using the randomization function in REDCap stratifying on site 
and diabetes status and using randomly permuted blocks of random sizes for the randomization to 
achieve balance in the participant allocation.  
 
Unblinding Plan 
 
As an open-label study, participants, providers, and many study staff will know to which group individual 
participants have been randomized. The investigative team, MPIs and Co-Is, (excluding the study 
statisticians Daniela Sotres-Alvarez and David Couper) will be blinded to group assignment of any 

 
 
 
40 
aggregated outcome data available before the completion of all data collection. Drs. Sortres-Alvarez and 
Couper will not be blinded to study groups as their reports prepared for the DSMC will include 
unblinded data.  Any key decisions by the study investigators (excluding the biostatisticians) regarding 
study outcomes, the appropriateness of test statistics or model assumptions, changes to this analysis 
plan, or any other statistical issues will be made in a masked review of the data (i.e., masked to the true 
randomization groups).  
 
A randomization table (using randomly permuted blocks of random sizes for the randomization to 
achieve balance in the participant’s allocation) will be prepared by the study statistician.  This will be 
updated to the REDCap system by Drs. Sortres-Alvarez.  Only study biostatisticians will have access to 
this table. Outcome datasets provided to the statistician by the data management team will include the 
randomized arm assignment. Other study investigators will not have access to the primary outcome 
data until all data have been collected.  
6.4 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
 
Adherence to the intervention 
• 
Twenty percent of counseling visits, selected at random, will be recorded and a subset of these 
reviewed to assess counselor adherence to the study protocol.   In addition, the counselor will 
complete a brief questionnaire after each counseling session to record his/her observations 
about the process of the counseling session. This questionnaire will also be part of our 
assessment of fidelity.  
• 
The extent to which participants perform weight management behavioral skills and cognitive 
strategies,136 will be assessed from questionnaire data addressing self-monitoring of weighing, 
dietary behaviors, and goal-setting (instruments listed in the Measurement Table, Section 8.1.2). 
 
6.5 
CONCOMITANT THERAPY 
Participation in this study does not preclude use of medications that are associated with weight loss. 
FDA approved weight loss medication will be allowed in both intervention and usual care groups, if 
recommended by the participant’s clinician. Similarly, medications for diabetes associated with weight 
loss (SGLT2 inhibitors and GLP1 agonists) may be used during this study.  We will specifically address use 
of these medications at all measurement visits. If an imbalance in use occurs across study groups, we 
will account for this in our sensitivity analyses.  
Bariatric Surgery 
At enrollment, we assess interest in bariatric surgery and if a potential participant is contemplating this 
within the next year, he/she will not be enrolled.  That said, a patient may elect to have bariatric surgery 
at any time during his/her participation in this study.  If a participant has bariatric surgery, he/she will be 
withdrawn from the study at that time.  Data collected prior to withdrawal will be included in the 
analysis.  
 
6.5.1 RESCUE THERAPY 
 
No rescue therapy outside of the study protocol is planned if participants do not lose weight.  

 
 
 
41 
 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
The study intervention will not be discontinued unless the participant withdraws or is withdrawn as 
outlined in the above section. 
 
If a participant withdraws or is withdrawn, no attempts will be made to collect follow-up measures.   
 
If a participant requests to withdraw from the intervention but is willing to continue the measurement 
component of the study, he/she will be invited to continue with follow-up measures.  
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY  
 
Participants are free to withdraw from participation in the study at any time upon request. 
 
Participants will be withdrawn according to protocol for the following reasons: 
• 
New diagnosis of condition on study entry exclusion criteria list (type 1 diabetes and cancer, as 
defined on the list).  
• 
Other medical diagnosis typically associated with significant weight loss (5% or more of body 
weight).  In addition to malignancy, examples include nonmalignant gastrointestinal disease, 
endocrinopathies, infectious disease, rheumatologic diseases, etc.  As Dr. Berkowitz (study Co-I, 
general internist) will be blinded to participants’ study group assignment, he will adjudicate in 
these situations, seeking consultation from medical colleagues as appropriate.  
• 
New diagnosis of cognitive decline confirmed by PCP as sufficient to interfere with insight 
related to food selection. 
• 
New diagnosis of medical condition such that participation in a behavioral weight loss 
intervention is no longer appropriate.  
• 
Permanent change in living situation (e.g. from home to nursing home) such that the participant 
has limited food options. 
 
Pregnancy:  Study participants who become pregnant may continue to participate in the study with the 
understanding that weight loss goals will be suspended during pregnancy through 3 months postpartum. 
If a pregnant participant wishes to continue with counseling session during pregnancy, the focus on 
counseling will be on dietary quality.  The participant may resume full participation 3 months 
postpartum. Any data collected while the participant is pregnant will be censured and follow-up data 
will not be collected until the participant is 6 months postpartum.  
 
 
A participant will be considered lost to follow-up if we are unable to contact him/her according to this 
algorithm.   
• 
Attempts at telephone contact: 

 
 
 
42 
o We will call up to 5 times over a 2 week period. We will attempt 2 calls during regular 
work hours (8:30 to 5:30 on weekdays) and 3 after hours, including Mon-Thurs evening 
between 5:31 and 9:00 pm and on Saturday calling between 8:30 and 5:30 pm.  
o We will leave up to 2 phone messages. 
o If no contact is made over this initial 2 week period as outlined above, we will undertake 
more limited contact attempts for an additional 2 weeks including up to 2 phone calls 
per week, 1 during business and the other  during evening hours or on the weekend.   
• 
Email:  If a participant gives us permission to contact by email, we will send up to 4 weekly 
emails. 
• 
Text:   If a participant gives us permission to contact by text, we will send up to 4 weekly texts. 
• 
Alternative contact:  During enrollment, we will collect information on an alternative contact 
that we are given permission to contact. We will attempt to contact this individual up to 3 times 
a week for 4 weeks. 
 
No replacement is planned for those who withdraw from the intervention for the study.  
 
7.3 
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if we are unable to contact him/her according to this 
algorithm.   
• 
Telephone contact: 
o We will call up to 5 times over a 2 week period. We will attempt 2 calls during regular 
work hours (8:30 to 5:30 on weekdays) and 3 after hours, including Mon-Thurs evening 
between 5:31 and 9:00 pm and on Saturday calling between 8:30 and 5:30 pm.  
o We will leave up to 2 phone messages. 
o If no contact is made over this initial 2 week period as outlined above, we will undertake 
more limited contact attempts for an additional 2 weeks including up to 2 phone calls 
per week, 1 during business and the other  during evening hours or on the weekend.   
• 
Email:  If a participant gives us permission to contact by email, we will send up to 4 weekly 
emails. 
• 
Text:   If a participant gives us permission to contact by text, we will send up to 4 weekly texts. 
• 
Alternative contact:  During enrollment, we will collect information on an alternative contact 
that we are given permission to contact. We will attempt to contact this individual up to 3 times 
a week for 4 weeks. 
 
If we are unable to contact a participant as outlined above, a letter will be sent to the current mailing 
address in the EHR outlining our attempts to contact the participant and inviting the participant to 
contact us if he/she still wishes to participate in this study.   
  
Should the participant continue to be unreachable and does not respond to the mailed letter within 4 
weeks, he or she will be considered to have withdrawn from the study with a primary reason of lost to 
follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 

 
 
 
43 
8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
 
8.1.1:  Screening, eligibility assessment, and consent 
• 
Outlined in detail in Section 5.5, Strategies for Recruitment and Retention.  
 
8.1.2:  Overview of study measures 
 
Study data will be collected at baseline, 4, 12, and 24 months. Process data for the intervention group 
(Med-South Weight Loss Program) will be collected as part of the intervention via the web-based 
platform and via REDCap questionnaires completed by counselors immediately after counseling 
sessions. Process data for the enhanced usual care group will be assessed via a Data Use Agreement 
with WW™ and by questionnaire at follow-up visits. As recommended by NIH, our measures include 
ADOPT137-139 core constructs (in blue) and specific instruments (in blue underlined) as noted in the Table. 
 
Primary and Secondary Aims 1 and 2:  
 
Table 3:  Outcomes/ Measures 
Collection Time 
(min)  
Data collected times 
(months) 
Comment 
 
 
0 
4 
12 
24 
 
Weight (primary outcome), by electronic scale 
as the average of two measures, and height 
(baseline only). SECA 874 dr scales will be used 
and assessed monthly for accuracy with 
standardized weights.. 
5 
x 
x 
x 
x 
At study outset, 
seven standardized 
50 lb. weights 
certified for 
accuracy by NC 
state standards 
lab.* 
Secondary Outcomes 
Objective measures 
 
 
 
 
 
 
--Blood pressure by noninvasive automated 
monitor (Omron HEM-907XL, Vernon Hills, 
IL) with a first measure after seated for 5 
minutes and 2 repeat measures at 1-minute 
intervals 
10 
x 
x 
x 
x 
 
--Blood work:  performed by LabCorp 
• 
Fasting lipid panel: total cholesterol, 
triglycerides, HDL, and calculated LDL and 
VLDL.  If participants are unable to fast a 
non-fasting sample is collected with non-
fasting stat noted 
• 
A1c 
• 
Other chemistry: glucose, ALT, creatinine 
(if not previously checked in prior 2 years 
and only at baseline), and CRP 
10 
x 
x 
x 
x 
Creatinine collected 
at baseline for those 
without measure in 
preceding 2 years.  

 
 
 
44 
--blood work:  preformed in lab of Dr. Steve 
Hursting.  Serum and plasm specimens are 
frozen to – 80 C. immediately after collection 
and processing.  
• 
 interleukin (IL)-6, tumor necrosis factor 
(TNF)-alpha, and C-reactive protein (C-
RP) 
--skin carotenoids, Reflection Spectroscopy 
Device (“Veggie Meter”™)140-142 
5 
x 
x 
x 
x 
 
Questionnaires:   
 
 
 
 
 
These data collected 
before the actual 
visit, on-line via 
REDCap or by 
phone.  Window 
before baseline visit 
is 4 weeks.  Window 
before follow-up 
and after follow-up 
visits is is 2 weeks.   
--Demographics and medical history (baseline 
only) 
15 
x 
 
 
 
 
--Diet assessment:  diet quality,143  adapted 
PREDIMED checklist19, 96  
10 
x 
x 
x 
x 
 
--Detailed assessment of diet quality:  Willett 
Food Frequency Questionnaire144 
20-30 
x 
x 
x 
x 
 
--Physical activity and sedentary behaviors:  
GPAQ for physical activity and sedentary 
behavior,145 participant report of 
monitored steps  
5 
 
x 
x 
x 
x 
 
--Quality of life (EQ5D146)  
5 
x 
x 
x 
x 
  
--Food insecurity147  
2 
x 
x 
x 
x 
 
Diet Self-Efficacy Scale148  
3 
x 
x 
x 
x 
 
Weight Loss Self-efficacy Short-Form (WEL-
SF1)149, 150 
3 
x 
x 
x 
x 
 
Early Self-Weighing Questionnaire151 
1 
x 
x 
x 
x 
 
Self-Regulation: Dietary Self-Regulation 
(TSRQ)152 
3 
x 
x 
x 
x 
 
Three-Factor Eating Questionnaire153 
3 
x 
x 
x 
x 
 
Mindful Eating Questionnaire154 ** 
5 
x 
x 
x 
x 
 

 
 
 
45 
Perceived Stress Scale155 
3 
x 
x 
x 
x 
 
PHQ-8156 
3 
x 
x 
x 
x 
 
--Medications for high BP, high blood lipids, 
diabetes, and weight loss (self-report with EHR 
review) 
5 
x 
x 
x 
x 
 
--Adverse outcomes, CVD events, ER visits, and 
hospitalizations (follow-up only) 
5 
 
x 
x 
x 
 
--Acceptability (follow-up only) 
5-10 
 
x 
x 
x 
 
Diet and PA goals and success achieving goals 
(collected by web-based intervention platform 
and counselor) 
NA 
 
 
 
 
Collected after each 
counseling session 
in intervention 
group. 
Exploratory Outcome 
 
 
 
 
 
 
Stool microbiome (participants may elect not 
to complete this measure) 
NA 
x 
x 
x 
x 
First sample will be 
collected in the 2 
week period 
immediately after 
randomization. 
(These are the only 
baseline data 
collected after 
randomization.) The 
follow-up samples 
will be collected 
w/n a 2 week 
window of follow-
up visit date. 
Other 
 
 
 
 
 
 
--EHR to assess/confirm adverse health 
outcomes  
NA 
 
x 
x 
x 
To confirm 
information 
collected by 
questionnaire at 
these visit time 
points 
* http://www.ncagr.gov/standard/Labs/ 
**Added to baseline on 12/22/20.  No follow-up data had been collected at this point in the study.  
Note:  table last updated 3/1/21 
 
Additional Study measures—economic outcomes 
 
The budgetary impact assessment and numerator for the cost effectiveness analysis will be based on 
Activity Based Costing Questionnaires previously developed and applied by Dr. Finkelstein in similar 
studies99, 157 along with participants’ health care claims data that will be used to compare resource 

 
 
 
46 
utilization between the intervention and control groups. The denominator for the cost effectiveness 
analysis will focus on weight loss (kg) and health related quality of life as assessed using the EQ-5D-5L.146  
 
8.1.3:  Detailed protocol for data collection 
 
8.1.3a:  Protocol Updated 3/16/21:  Study visits after hospitalization. 
• 
Enrollment and follow-up measurement visits:   
o May occur 2 or more weeks after hospital stay if less than 7 days (defined as 2-7 nights 
in the hospital). 
o May occur 30 or more days after hospital stay of more than 7 days (defined as 8 or more 
nights in the hospital). 
o Note: ER visits and 1 night in the hospital (often defined as observation) do not count as 
hospitalization.  
• 
Counseling sessions: 
o 
No interval specified.  To be determined by counselor and participant. 
 
 
Note:  Research staff will be trained and periodically retrained on data collection protocols. Baseline 
training will include detailed review of and practice with protocols under the direction of the study’s 
MPIs, Study Manager, and Data Manager. Retraining will occur at quarterly intervals.  
 
8.1.3.1: Weight and height protocols  
• 
At study outset, weights (seven 50 pound weights) assessed and adjusted for accuracy on 
12/3/19 by North Carolina Department of Agriculture and Consumer Services Standards 
Laboratory. 
• 
Weights to be re-assessed and adjusted for accuracy annually. 
• 
Scales tested for accuracy the first week of each month during their use in this study.  
 
Seca 874 dr Scale Tolerance Testing 
(updated 1/28/20) 
 
The scale's 6 AA batteries should be replaced at least once a year. 
It is imperative that tolerance weights be handled carefully (no slamming around or banging against one 
another) to maintain their accuracy.  
Before starting the test set the ON-OFF switch to ON.  Press the start key with no load on the scale.  If 
necessary switch the weight display from kg to lbs by pressing the 2 in 1 key for approximately 3 
seconds.  
1) Place a 50 lb wt in the center of the scale and record weight. (~50 lbs)  Remove the 50 lb wt. Press 
start key. 
2) Carefully stack two 50 lb wts on top of one another in the center of the scale.  The first weight must 
be gently vibrated until the second is in place to prevent the scale from prematurely locking in and 
giving an erroneous reading.  Record the weight reading (~ 100 lbs).  Press the 2 in 1 key. 

 
 
 
47 
3) Place a third 50 lb wt on the scale and record weight. (~50 lbs  The sum of this weight and the weight 
observed in step 2, ~ 100 lbs,  is the observed reading for the expected weight of 150 lbs )  Remove 
the top 50 lb wt. only. 
 4) Place two 50 lb wts on top of the two remaining weights vibrating the stack as before.  Record the 
weight reading (~ 100 lbs The sum of this weight and the weight observed in step 2, ~ 100 lbs,  is the 
observed reading for the expected weight of 200 lbs).  Remove all four weights.  Press start key. 
5) Carefully, but quickly, stack five 50 lb wts on top of one another in the center of the scale, gently but 
firmly vibrating the stack until the fifth weight is added.  Record the weight reading (~ 250 lbs).  Press 
the 2 in 1 key.    
6) Place a sixth 50 lb wt on the scale and record weight. (~50 lbs  The sum of this weight and the weight 
observed in step 6, ~ 250 lbs,  is the observed reading for the expected weight of 300 lbs)  Remove the 
top 50 lb wt. only. 
7) Place two 50 lb wts on top of the five remaining weights vibrating the stack as before.  Record the 
weight reading (~ 100 lbs The sum of this weight and the weight observed in step 6, ~ 250 lbs,  is the 
observed reading for the expected weight of 350 lbs).  Remove all weights. 
8) Set ON-OFF switch to OFF. 
 
During the testing if any observed reading falls outside the tolerance range repeat the testing steps to 
verify the reading.  No need to continue testing the scale if a weight is out of range and verified.   Scales 
failing the tolerance testing should no longer be used.  
 
lbs 
0.40% 
 
 
Tolerance 
 
 
Limit  
Range 
 
 
50 
0.2 
49.8 - 50.2 
100 
0.4 
99.6 - 100.4 
150 
0.6 
149.4 – 150.6 
200 
0.8 
199.2 – 200.8 
250 
1 
249.0 – 251.0 
300 
1.2 
298.8 – 301.2 
350 
1.4 
348.6 – 351.4 
 
 
Scale S/N 
  

 
 
 
48 
Date 
    
Expected 
Observed  
Difference 
0.40% 
Weight (lbs.) 
Weight (lbs.) 
(lbs.) 
Tolerance 
Limit 
(lbs.) 
50 
  
  
0.2 
100 
  
  
0.4 
(50)  
 
 
 
 
 
150 
  
  
0.6 
(100)  
 
 
 
 
 
200 
  
  
0.8 
250 
  
  
1 
(50)  
 
 
 
 
 
300 
  
  
1.2 
(100)  
 
 
 
 
 
350 
  
  
1.4 
 
 
WEIGHT MEASUREMENT PROTOCOL 
(last updated 10/28/19) 
 
Prior to the appointment the participant is instructed to wear light clothing and informed that 
the weight measurements will be made with shoes removed. 
 
 
Materials 
• Seca model 874 dr electronic personal scale 
 
Preparation  
• Place the scale on a hard level surface. 
• Turn the scale ON with the ON-OFF switch.  Press the start key with no load on the scale.  
The scale is automatically set to zero and ready for use. 
• Once the digital display reads zero verify that “lbs” unit is showing.  If “kg” appears in the 
display press the 2 in 1 key for approximately 3 seconds. "lbs” should then show in the 
display.  
 
Procedure 

 
 
 
49 
Participant 
• With shoes removed, scale displaying zero; step onto the middle of the scale. 
• Stand on both feet, knees extended (straight) with arms by sides.  
 
Research Staff 
• Once the reading in the digital display is stable, record the first weight on the Weight 
Measurement Form in lbs, recording the tenths of lb (i.e. 81.4 lbs). 
• Have the participant step off the scale. 
• Have the participant step back onto the scale once zero is displayed.  Note: You may need 
to restart the scale by pressing the start key to obtain the zero and lbs display before 
instructing the participant to step back onto the scale. 
• Once the reading in the digital display is stable, record the second weight on the form. 
• Record the difference between the first and second readings. 
• If the difference is greater than 1 lb repeat and record a third weight. 
• When finished weighing participants turn the scale OFF with ON-OFF switch. 
 
Note  
• A stabilized reading in the scale display is needed for recording.  The participant needs to 
stand very still while breathing naturally.  If moving too much the weight will not stabilize in 
the display.     
Scale Accuracy Testing 
• To insure accuracy the scales have been tested using certified tolerance weights.  
(Performed by research center staff each month).  
• Staff should weigh themselves whenever the scale is set up for participant measurement  
 
Scale Care 
• Treat the scale as a laptop. Do not bump against other objects or expose to extreme 
temperatures.  
• Store in the horizontal position without stacking anything on top. 
• Do not allow anyone to weigh without your supervision and instructions. 
• When not using, turn the ON-OFF switch to OFF to conserve the battery. 
 
8.1.3.2: Height Protocol  
 
HEIGHT PROTOCOL 
(last updated 1/28/20) 
 
Prior to the appointment the participant is instructed to wear light clothing and informed that 
both height and weight measurements will be made with shoes off. 
 
 
Materials 
• Shorr infant/child/adult stadiometer 

 
 
 
50 
 
Procedure 
Participant 
• Shoes removed. 
• Back to the height board, heels all the way to the back. 
• Standing up straight with arms by sides (Evaluate posture to be sure participant is standing 
upright, flat-footed and looking straight ahead with head in the Frankfort horizontal plane, 
the horizontal plane which includes the lower margin of the bony orbit--the bony socket 
containing the eye--the most forward point in the supratragal notch--the notch just above 
the anterior cartilaginous projections of the external ear).  See “Frankfort Plane for 
Measuring Body Height” diagram. 
9 Research Staff 
• Lower the sliding headpiece onto the participant’s head. 
• Read the measuring scale of the stadiometer to the nearest 1/8th inch (Note: stadiometer is 
scaled in inches, not centimeters). 
• Two measures are taken and recorded on REDCap form.  The participant steps off the 
stadiometer between measures.  If the two measures differ by >1/4 inch a third measure is 
taken and recorded in the “blank” for the 3rd observation. 
• Height is determined from the 2-3 observations (the average of the 2 closest 
measurements, rounding up to nearest 1/8th inch) and recorded on the form. 
• Record your staff ID number on the REDcap form. 
 
Notes: 
• If the participant is breathing heavily enough to cause oscillations in the sliding headpiece, 
you must wait until s/he has settled down or ask to exhale and hold breath. 
• If the participant’s hairstyle interferes with measurement, be flexible and creative and get an 
accurate measurement (i.e. remove ponytail holders, measure hair height with tape measure, 
flatten hairdo, etc.). 
• If the participant’s buttocks cause an irregular or very unnatural posture when the heels are 
against the back of the board, allow standing with feet under hips (heels will not be against 
the back of the board in this case). 
 

 
 
 
51 
 

 
 
 
52 
 
8.1.3.2: Blood pressure protocol 
 
BLOOD PRESSURE PROTOCOL 
(updated 1/28/20) 
 
Warnings 
• 
Do not share an electric outlet with another unit or electric appliance. 
• 
Keep unit at least 5 feet from cell phones and computers. 
• 
Unplug AC adaptor from electric outlet if unit is unused for an extended period of time. 
• 
Do not inflate the cuff without being wrapped over the arm. 
• 
Do not store unit under high temperature and high humidity. 
• 
Transport the unit inside a car, not in the trunk. 
 
 
 
Materials 
• 
Omron Model HEM-907XL blood pressure monitor with small, medium, large, and extra large cuffs 
 
• 
Tape measure 
 
Note:  The Omron cannot be used on arms with a circumference greater than 17” (large Omron cuff 
does not fit) or if the Omron is unable to take the measurement.  
 
Procedure using the Omron 
Set up 
• 
Connect the AC adapter to the DC jack of the main unit and the electric outlet. 
• 
Connect the air tube to the main unit by securing the air plug to the base of the air connector.  This 
air tube is for use with the small, medium, and large cuffs only.  The extra large cuff has its own non-
detachable air tube for connection to the main unit. 
 
Participant 
• 
Should avoid caffeine, exercise, and smoking for at least 30 min before measurement. 
• 
Invite participant to empty bladder before measurement . 
• 
Shirt, blouse, or dress sleeves are loose fitting enough not to cause constriction of the arm even 
when pushed up for wrapping the cuff onto the bare arm.  If too tight, the arm needs to be placed 
outside the sleeve.   
• 
Remains quietly seated in a chair with both feet flat on the floor and back supported while 
measurements are taken.  Neither the participant nor the staff should talk during the 5 min rest 
period or during the measurement.  
 
Research Staff 
• 
Apply the cuff to the right arm of the seated participant.  All BP measurements are made using the 
right arm unless prevented by injury or deformity.  If the left arm is used it is indicated on the BP 
and Heart Rate (BPHR) form and subsequent BP measures are taken using the left arm.  See “How to 
Apply the Cuff” diagram. 

 
 
 
53 
o Measure the circumference of the largest part of the upper arm and select the cuff according to 
arm size. 
◂ 
7”-9” small 
◂ 
9”-13” medium 
◂ 
13”-17” large 
◂ 
17”- 20”extra large 
o Connect the air tube and the cuff/bladder set by rotating the Luer connection. 
o Place the participant’s hand with the palm upward. 
o Align the Artery Position Mark on the cuff with the brachial artery. 
o Wrap the cuff snugly using both hands and securely fasten it with the Velcro™ tape.  The lower 
edge of the cuff should be placed ½” to 1” above the inner side of the elbow joint. 
◂ 
If the INDEX is positioned outside the RANGE, select the cuff suitable for the patient’s 
arm circumference and wrap it again.  Wrap the cuff so that you can insert only one 
finger between the cuff and arm.  If the upper arm is more pyramid shaped rather than 
cylinder shaped it is necessary to wrap the cuff in a slightly diagonal fashion so that both 
the upper and lower borders of the cuff fit snugly against the skin. 
o Keep the level of the cuff at the same level as the heart during the measurement.  The 
participant should sit upright in the chair, not slouching, with arm supported (eg, resting on a 
desk)..   
• 
Take the blood pressure. 
o Push the ON/OFF (power) BUTTON to turn on the power. 
o Set the MODE Selector to “AVG”.  The monitor has been programmed to: 
◂ 
Wait 5 min. until the 1st measurement. 
◂ 
Take 3 measurements. 
◂ 
Wait 1 min. between measurements. 
o Set the P-SET (inflation level setting) Knob to “AUTO”. 
o Push the HIDE button for non-display of results. 
o Push the START Button to begin measurement.  The 5 minute countdown will be displayed.  
After 5 minutes the monitor takes the first measurement and then displays the results.  One 
minute later the 2nd measurement is taken.  The monitor takes the 3rd and final measurement 
after another minute.   
◂ 
To stop a measurement, push the STOP Button.  The unit will rapidly deflate. 
◂ 
Do not push the START Button without first wrapping the cuff around the participant’s 
arm. 
◂ 
If an error occurs during measurement, the monitor will automatically start 
measurement again.  If a second error occurs, measurement will automatically stop. 
◂ 
If the monitor determines that the pressure value is not correct, an error display 
appears (Er1 to 9).  In this case, refer to Page 28 of the manual and start the 
measurement again. 
◂ 
If the blood pressure is unattainable using the monitor the measure will be missing.   
Note this on the form by checking appropriate option 1) arm circumference greater 
than 17” 2) Omron unable to measure.  
o Push the HIDE button for display of results. 
 
• 
Enter measurement results on the form. 
o After all 3 measurements are completed; the average value will be displayed. 

 
 
 
54 
o Enter the average pulse rate (BPM) on the form. 
o Press the DEFLATION (deflation control) /Measurement Result Display Switch Button to display 
the 1st measurement for entering. 
o Press the same button again to display the 2nd measurement for entering. 
o Press the button again to display the 3rd measurement for entering. 
• 
Push the ON/OFF (power) Button to turn off the power. 
• 
Mark right/left arm and record your staff ID number on the form. 
 
Blood Pressure Feedback Card 
• 
Fill in the date and the average of the 3 readings. 
• 
Check a blank for recommendation if appropriate. 
• 
Give to participant and point out any checked recommendation. 
• 
If blood pressure is > 140/90 we will recommend the following:  
• 
140-159/90-99 [Check with your clinician within 2 months.]  
• 
160-179/100-109 [Check with your clinician within 1 month.]  
• 
180-219/110-129 [Check with your clinician within 1 week.] Also, staff will send Epic note to primary 
care clinician. 
• 
Greater than 220/130 [Check with your clinician within 24 hours.] Also, staff will send Epic note to 
primary care clinician. 
• 
*If the systolic and diastolic pressures are in different categories, follow the recommendations for 
the category with the shortest follow-up interval 
 
8.1.3.3: Blood specimen collection protocol 
 
Collection of Blood Specimens 
(drafted 11/26/19) 
 
This document outlines the lab protocols for this study.  It is organized into 2 sections:   
• 
Lab work that will done by a commercial laboratory and generally considered routine clinical lab 
tests 
• 
Special research lab tests 
 
Routine Clinical Labs Tests 
• 
This lab work will be performed by LabCorp (Burlington, NC).  As our negotiated pricing is 
favorable, we are able to do some additional testing not included in our NIH proposal, as 
outlined below.  
• 
Lab measurement time points:  baseline and 4, 12, and 24 months follow-up.  Routine clinical 
lab tests will be collected at all time points, except for creatinine as noted below.  Note, in the 
proposal, non-fasting blood work was proposed, but we have modified the protocol to collect 
fasting blood work.  
• 
Lab tests to be done as outlined in the proposal 
o total cholesterol, HDL cholesterol, A1c, CRP, creatinine (on participants who do not have 
a creatinine in the medical record within the last 2 years, baseline only) 
• 
Additional lab tests 
o Fasting glucose -- with the decision to collect a fasting sample, we might observe 
changes in fasting glucose and this test will allow for calculation of HOMA-IR 

 
 
 
55 
o Triglycerides -- with the decision to collect a fasting sample, we might observe changes 
in triglyceride levels and having triglycerides will allow us to calculate LDL.  
o ALT – we will use as single lab test as a crude monitor of fatty liver 
 
Test Collection and Sample Stability Information (as outlined on LabCorp website) 
 
 
Collection Protocol 
• 
Participants will be asked to fast for 9 hours before blood collection.  Liquids w/o calories are 
acceptable as is taking medication. Those with diabetes will be instructed to bring a snack with 
them in case they experience low blood glucose.   
• 
If participant has not fasted for at least 9 hours, he/she will be re-scheduled for another time. 
• 
The LabCorp requisition and 2 tube labels will already be filled out by study staff with the 
exception of SPECIMEN DATE and SPECIMEN TIME (Collection Date and Time for labels).  These 
will need to be filled in by lab personnel. Note:  lab for routine clinical lab tests will include 
identifying data including participants name and date.  The report from LabCorp will be entered 
into the UNC electronic medical record as a scanned document.  The specimens will be 
discarded according to the standard operating procedures of LabCorp.  
• 
Lab personnel will need to fill in their first and last initials in the appropriate boxes for tubes 
collected on the LabCorp Specimen Collection form.  
• 
Using standard phlebotomy technique, collect: 
o 8.5 cc SST (gel) tube (total cholesterol, HDL Cholesterol, triglycerides, glucose, ALT and 
creatinine).  After collection: 
 
Gently invert the gel-barrier tube 5 times to mix the clot activator and blood 
 
Place the collection tube in the upright position in the rack, and allow the blood 
to clot at room temperature for 30 to 60 minutes (aim for 45 minutes). 
(Minimum clotting time is 30 minutes for patients with an intact clotting 
process.) 
 
After allowing the clot to form, insert the tube in the centrifuge, stopper end up. 
Operate the centrifuge for 10 minutes at the speed recommended by the 
manufacturer. Prolonged centrifugation may cause hemolysis. Do not exceed 10 
minutes of spin time unless otherwise specified. 
Test 
Code 
Tube 
Preparation 
Vol. 
Temp 
Stable 
Total 
cholesterol 
001065 
Gel 
barrier 
Separate serum or 
plasma from cells 
within 45 minutes of 
collection 
.5 ml 
room 
14 days 
HDL 
cholesterol 
001925 
As above 
As above 
.5 ml 
Room  3 days 
Triglycerides  
001172 
As above 
As above 
.5 ml 
Room  7 days 
Creatinine 
001370 
As above 
As above 
.5 ml 
Room  14 days 
Glucose 
001032 
As above 
As above 
.5 ml 
Room  14 days 
ALT 
001545 
As above 
As above 
.5 ml 
Room  7 days 
CRP 
006627 
As above 
Not stated 
1 ml 
Room  14 days 
A1c 
001453 
Lavender 
top 
Not needed 
4 ml stated; ped 
tube may be 
used 
Room 14 days 

 
 
 
56 
 
Turn the centrifuge off, if not an automatic turn off, and allow it to come to a 
complete stop. Do not stop it by hand or brake. Remove the tube carefully 
without disturbing the contents. Inspect the barrier gel to ensure that it has 
formed a solid seal between the serum and packed cells. 
 
It is not necessary to transfer serum to a plastic transport tube. Serum 
specimens may be sent at room temperature. 
o 3cc lavender-top tube (Hgb A1c) 
 
No centrifugation needed. 
o Process as usual for LabCorp pick-up (samples do not need to be refrigerated) 
 
Study research staff will notify LabCorp if courier does not stop by daily.  
 
Special Research Labs Tests 
• 
Special research tests to be performed as outlined in the proposal 
o Inflammation:  IL-6, TNF-a, CRP (CRP will be done as part of the clinical lab work, as 
above) 
• 
Additional research tests that may be done:  
o Energy homeostasis:  adiponectin, leptin [could also consider amylin] 
o Hunger/satiety:  Ghrelin – [could also consider Glucagon-like peptide (GLP)-1, PYY] 
o Metabolic function:  insulin to assess insulin sensitivity (HOMA-IR, based on glucose and 
insulin level) 
 
The collection protocol for blood specimens to be assessed for special research tests as outlined above 
requires freezing at -80 C. as promptly as possible. Within the Chapel Hill catchment area, which will 
include at least ½ of the study participants, plasma and serum specimens will be collected in a setting 
where collection time to placement in a -80 C. freezer will be approximately 20-30 minutes for plasma 
and 40 minutes for serum samples. Outside of the Chapel Hill catchment area, it may not be possible to 
collect specimens and move to cold storage in this time frame.  
 
All participants in both catchment areas will have a sample collected to be stored for potential future 
DNA analysis.  
 
Tubes will be pre-labelled.  Tubes for cold storage will include PT ID#, date of collection, and first and 
last initial.  Tubes for DNA collection will include PT ID#, date of collection, but NO initials.  
 
Plasma Cold Storage:  6 cc green-top (sodium heparin) vacutainer for plasma  
• 
Tap the tube gently to release additive adhering to the tube or stopper diaphragm. (See Figure.) 
 
• 
Permit the vacuum tube to fill completely. Failure to fill the tube will cause an improper blood-
to-anticoagulant ratio and yield questionable and/or QNS test results. 

 
 
 
57 
• 
To avoid clotting, mix the blood with the anticoagulant or preservative immediately after 
drawing each sample. 
• 
To allow adequate mixing, slowly invert the tube eight to ten times using a gentle wrist rotation 
motion. 
• 
Immediately centrifuge the specimen for 20 minutes (room temperature is acceptable). 
Do not remove the stopper. 
• 
Turn the centrifuge off, if not an automatic turn off, and allow it to come to a complete stop. 
Do not stop it by hand or brake. Remove the tube carefully without disturbing the contents. 
• 
Remove the stopper and carefully aspirate plasma, using a separate disposable Pasteur pipette 
for each tube. 
• 
Place the tip of the pipette against the side of the tube, approximately ¼ inch above the cell 
layer. Do not disturb the cell layer or carry any cells over into the pipette. Do not pour off; use 
transfer pipette. 
• 
Using the pipette transfer 1.5-1.75 ml plasma to each of two 2 ml cryovials, capping one with a 
YELLOW cap and one with a BLUE cap.    
• 
Place in study storage box in -80 C. freezer according to color of vial cap.  There will be a box for 
each color.  
 
Serum Cold Storage:  8.5 cc SST (gel) tube   
• 
Prepare using protocol for gel tube outlined above.  
• 
Transfer 1.5-1.75 ml of serum to each of two 2 ml cryovials, capping one with a GREEN cap and 
one with a RED cap.   
• 
Place in study storage box in -80 C. freezer according to color of vial cap.  There will be a box for 
each color.  
 
DNA:   10 cc PAXgene Blood DNA tube (collects 8.5 ml blood) 
• 
Should be the last tube drawn in a series of tubes 
To guard against backflow: 
 
Place participant’s arm in a downward position 
 
Hold tube with the stopper uppermost 
 
Make sure tube additives do not touch stopper or end of the needle 
during venipuncture  
 
• 
After collection gently invert the tube 8-10 times 
• 
For locations with access to -80 C freezer.  Place in box in Freezer. 
• 
For locations without access to -80 freezer.  Store tube upright at room temperature.  
Will ship every 2 weeks to Dr. Steve Hursting’s lab for storage at -80 C.  
 
Note:  Transfer of specimens to Dr. Steve Hursting’s lab at the UNC Gillings School of Public Health 
• 
Specimens stored in cold freezers with generator backup will be transferred on dry ice to the 
Hursting lab approximately 2 months. 
• 
Specimens stored in cold freezers without generator backup will be transferred on dry ice to the 
Hursting lab every 2 weeks.  Update 3-25-21:  Transfer may be up to every 6 weeks depending 
in part on number of specimens collected. 
 
8.1.3.3a:  Lab Protocol Update 3-25-21: 

 
 
 
58 
• 
Protocol amended 9-17-20 re baseline phlebotomy.  If unable to get blood specimens on 
randomization day due to lack of success by phlebotomist and if participant agrees, will allow for 
return phlebotomy within 10 days.   
• 
Protocol amended 3-25-21 re blood work collection by UNC Phlebotomy.  
o If study phlebotomist/staff unable to obtain blood after a minimum of 3 tries, 
participant may go to UNC phlebotomy lab for blood draw within 10 days, but 
preferably w/n 3 days.  From campus site, there will be a 10-15 min delay in processing.  
From Eastown site, there will be about a 10 min delay in processing. 
o If study phlebotomist/staff are not available for a measurement visit, participant may 
stop by UNC lab to have study phlebotomy done before coming to study office for the 
measurement visit.  The samples will be brought to the research office promptly for 
processing.  
Protocol specification note 3-25-21.  If we are unable to obtain baseline blood work, we will not 
attempt to obtain follow-up blood work.  For 2 reasons:  first, likelihood of success on follow-up may be 
low as “difficult stick” and second, no baseline for comparison. 
 
8.1.3.4: Veggie meter protocol    
 
Veggie Meter (RS-Assessed Skin Carotenoid Device) Measurement Protocol 
(updated 1/26/20) 
Objective 
Participant skin carotenoids will be assessed using a pressure-mediated reflection spectroscopy (RS) 
device (Veggie Meter). RS uses broad-band white light to measure skin carotenoids directly through 
their respective absorptions from 400-750 nm. Reflected light is routed to a spectrograph coupled with a 
room-temperature detector array. The RS device measures finger skin tissue and adjusts for potentially 
confounding effects of melanin and hemoglobin. Participants will clean their hands with soap and water, 
the right index finger will be scanned 3 times and the average value will be used in our analysis. Each 
scan take ~3 seconds. Regarding RS cross-calibration to ensure comparability across the NC and MN 
sites, each RS Device comes with a standard calibration method that is used for all devices. In order to 
assess reliability (reproducibility of the measure), we will use the same strategy used in our small validity 
paper, 61 wherein RS measures are taken three times in the same person at the same time point, and we 
will calculate reliability. 
 
To use the Veggie Meter, the finger is inserted into the instrument’s finger cradle to a) bring the pad of 
the fingertip in close contact with a light delivering and collecting contact lens, and b) to gently apply 
pressure to the finger such that blood is temporarily squeezed out of the measured skin region. A laptop 
computer interfaced to the instrument analyzes the light that is reflected from the finger, and 
subsequently derives a carotenoid score. The measurement takes 10 or 45 seconds, depending on 
whether a single- or multiple measurement mode is chosen, respectively. In multiple measurement 
mode, the finger is inserted and retracted three times and an average score is determined for the three 
measurements.  In this study, we will use single-measurement mode, and will ask participants to insert 
and reinsert their fingers three times. Since carotenoid levels differ slightly between fingers, always 
measure the same finger when tracking changes. For this study’s purposes, we will use the right index 
finger. 

 
 
 
59 
 
Veggie Meter Supplies and Calibration 
1. Supplies 
a. The Veggie Meter consists of a box shaped base or pedestal that contains the 
electronics and an oval-shaped housing unit on top of the base that provides an optical 
interface for the fingertip to be measured (see Figure 4). 
b. Two cables (gray and black) 
c. Laptop 
d. Stopwatch 
e. Note that the Veggie Meter is highly sensitive so avoid exposure to excessive heat and 
bright light. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2. Device Calibration  
a. Prior to skin measurements, connect the two cables of the Veggie Meter with the USB 
ports on the laptop. The gray cable from the base goes into the back port and the black 
cable from the housing goes into the front port. Note that the two USB ports are NOT 
interchangeable (see Figure 5). 
Figure 4. Veggie MeterComponents

 
 
 
60 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
b. Connect the laptop with the power outlet or run the Veggie Meter/laptop system on 
battery for a few hours. 
c. Power up the laptop by pressing and releasing the power button located above the 
keyboard on the right. 
d. Tap on the mouse pad to activate user screen and enter password “project”. 
e. Power on the Veggie Meter by pressing the power button in the back of the instrument 
housing. There are two buttons. The power button is the bottom button that sits above 
the black cable connection (see Figure 6). Ignore the top button. 
 
 
 
 
 
 
 
 
Figure 5 Veggie MeterSetup
Black and gray cables from 
h
i
d b
ti
l
Black cable in front 
Power Button

 
 
 
61 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
f. The Veggie Meter takes approximately 5 minutes to warm up. A color display on the 
top of the housing unit initially displays the number 5 and then counts down the 
remaining minutes (see Figure 7). After 5 minutes, the display goes dark.  
 
 
 
 
 
 
 
 
 
 
 
 
Figure 7. Veggie MeterWarm-up Display

 
 
 
62 
 
 
 
 
 
 
 
 
 
g. After the display has gone dark, move the computer cursor to the “Longevity_02_25_16 
Shortcut” icon on the computer desktop. Double click to activate the program. 
h. The Veggie Meter program window will now open. There are three panels: a) a top 
panel for entry of subject demographics; b) a right panel for selection of the desired 
measurement mode (“single scan” or “average of 3 scans”) and for the activation of 
calibration measurements (DARK REFERENCE and WHITE REFERENCE buttons); and c) a 
large display panel. The display panel is blank at the beginning. 
i. 
Gently slide the dark reference stick (see Figure 8) with its two side rails over the 
housing’s finger cradle such that the rails are pointing down and the black felt at the 
bottom of the stick is facing the lens and positioned a few millimeters above the lens. 
The stick should push against the two inside plastic pegs while protruding from the 
housing. While positioned properly, the instrument’s white LED light will illuminate the 
black felt. Keep felt clean. Do not touch it. Blow off lint/dust if needed. 
 
 
 
 
 
 
 
 
 
 
 
Dark Reference Stick
Figure 8 Veggie MeterDark Reference Stick

 
 
 
63 
 
 
 
 
 
 
 
 
j. 
After proper positioning, click on the DARK REFERENCE button located in the right panel 
of the program window. The display panel will now show the reflection spectrum for the 
dark reference. It should look similar to the spectrum shown below (Figure 9), consisting 
of a strong peak at about pix number 70 and a weaker, broad band, in the 80-200 pixel 
number region. The height/intensity of the strong peak which is indicated on the vertical 
axis should be ~10,000 ± 500. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
64 
 
 
 
 
 
 
k. Insert the white reference stick into the finger cradle such that the indentation in the 
white plastic material fits snugly over the contact lens. Make sure the white surface is 
pointing down. 
l. 
After proper positioning, click on the WHITE REFERENCE button in the right panel of the 
program window. A spectrum is displayed that should look similar to the one shown 
above, but smoother, consisting of a strong peak and a broad band. The intensity of the 
strong peak should be in the range of 42,000 to 56,000. 
m. Once calibrated, the instrument is ready for skin measurements. 
n. Be sure to calibrate the device after each participant’s three readings are completed. 
 
 
Veggie Meter Measurement  
1. Participant will be asked to wash hands with soap and water prior to measurement. 
2. Choose Single Scan mode in the Veggie Meter display window (we will have participant insert 
and re-insert finger three separate times, so do NOT choose Average of 3 Scans mode). 
3. Enter the participant’s ID# into the Subject ID field in the display window. Do NOT enter the 
participant’s name. 
4. . 
5. Please turn the Veggie Meter computer screen away from the participant to “blind” him/her to 
the output from the Veggie Meter scan.  
6. Ask the participant to insert his/her right index finger. The index finger should be positioned in 
the cradle such that the finger sits snugly into the indentation (see Figure 10). 
 
 
 
 
 
 
 
 
Fi
10 V
i M t
Fi
Pl
t

 
 
 
65 
 
 
 
 
 
 
7. Click on START. In Single Scan mode, the display window will first flash SCANNING IN PROGRESS, 
display a progress bar, and after finishing the scan, will show the Carotenoid Score on a scale 
from 0 to 800 (see Figure 11). 
8. In the display panel at the right, the measured score is compared with a histogram of scores for 
the general population. The histogram region corresponding to the measured score is shown in 
RED.  
9. Record the Veggie Meter value (i.e., Your Carotenoid Score) BEFORE clicking the Close button! 
Record all three of the values on the Tanita print out so the participant can review it after all 
measurements are completed. 
10. Click on the Close button to return to the measurements screen and start a new scan.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11. The measurement data are automatically saved in a folder on disk C called ResultsM. A shortcut 
is placed on the desktop. 
Fi
11 V
i M t
C
t
id S

 
 
 
66 
12. Note: The average carotenoid score is approximately 200. 
Veggie Meter Troubleshooting 
Sometimes the communication between computer and instrument can be lost. In those cases, 
corresponding measures will appear in the program window. To re-establish communication, exit the 
program and/or unplug and reconnect the instrument’s USB connections and start over. 
Veggie Meter Shut Down 
1. After the scores have been recorded for each participant on the data collection form, turn off 
the power on the Veggie Meter housing unit (low button in back). 
2. In the measurements screen, click on upper right window button (x) to close program window. 
In following Exit window, click on the OK button. 
3. Pull up main computer menu by sliding up on mouse pad, click on “Power” and “Shut down” on 
the following window. 
 
Stool Collection Protocol added 3/2/20 
 
Stool Collection and Shipping Instructions Important notes: 
1. 
Please read through all instructions before beginning the collection. 
 
2. 
Please only collect your sample on Sunday, Monday, or Tuesday. 
 
3. 
Please select a day when you do not have atypical diarrhea or constipation. We are interested in your 
usual bowel movement. 
 
4. 
Please ship your sample, or return your sample to the clinic, within 24  
    hours of collecting your sample. 
 
5. 
Please contact [study contact], at [study contact phone number],  
    if you have questions or if you will be returning your sample to   
    the clinic. 
 
Your collection kit contains the following items: 
  
1 Small shipping container with label (paper towels inside) 
  
3 Stool collection tubes with a brown caps 
  
3 Larger clear transport tubes with white caps 
 
  
3 Biohazard bags 
 
  
1 Stool collection commode kit 
 
  
1 Water-soluble bag (clear color) 
 
  
1 Bubble bag (clear color) 
  
1 Pair of disposable gloves (cream-color) 
  
1 Study questionnaire 
  
1 Blue zip-lock bag 
  
How to collect the stool samples: 
 

 
 
 
67 
 
  
 
 
 
STEP 1. 
 
• 
Lift the toilet seat and place the stool collection frame on the back of the toilet bowl. 
 
• 
All four corners of the collection frame should be supported by the toilet bowl. 
 
 
 
  
STEP 2. 
 
• 
Line the collection bowl with the water- soluble bag. 
  
 
 
 
STEP 3. 
 
• 
Place the toilet seat down. 
  
 
 
STEP 4. 
 
• 
Insert the lined collection bowl into the frame. 
  
  
 
 
 
 
 
 
 
STEP 5. 
 
• 
Place the collection tubes with the brown caps where you can easily reach them— near the toilet or on 
the back of the toilet. 
 
• 
After your bowel movement you will use these tubes to collect your stool sample. 
 
STEP 6. 
 
• 
Sit on the toilet as you normally would. Any stool passed should naturally collect directly into the lined 
collection bowl. 
 
• 
Please do not urinate into the collection container. If you do get some urine into the collection container, 
please select a sample from a part of the stool away from the urine. 
  
 
STEP 7. 
 
You will collect a total of 3 samples from the same stool: one sample in each of the 3 brown-capped collection 
tubes. 

 
 
 
68 
 
• 
Unscrew the brown cap from one tube. There is a scoop attached to the brown cap. 
 
• 
Please take care not to spill the contents of the tubes because they contain liquid sample preservative and 
glass beads. 
 
• 
Please hold the scoop by the brown cap only. Do not touch the scoop. 
 
• 
While holding the brown cap in your hand, place one full scoop of stool (pea sized) into the small clear 
tube.  
 
• 
Screw the brown cap back on tightly. 
 
• 
Repeat the above steps to collect two additional stool samples in the brown- capped tubes. 
  
 
STEP 8. 
 
• 
After collecting your samples, remove the water soluble bag from the collection bowl and place into the 
toilet. 
 
• 
The bag will dissolve, allowing you to flush your remaining stool. 
 
• 
The toilet frame, bowl, and lid can be discarded. 
  
 
 
 
STEP 9. 
 
• 
Place each brown-capped collection tube into one of the larger white-capped tubes. 
 
• 
You should have 3 collection sets. 
 
• 
Screw the caps tightly for shipping. 
 
STEP 10. 
 
• 
Please vigorously shake the tubes so that the stool mixes well with the sample preservative. 
 
  
 
STEP 11. 
 
• 
Place each of the large tubes inside a biohazard bag and seal the bag completely. 
 
  
 
STEP 12. 
 
• 
Place the 3 sealed biohazard bags with your stool samples into the bubble bag and seal. 
  
 
STEP 13. 
 
• 
Please complete the survey on the day of your collection. 
 
• 
Place the completed survey into the blue ziplock bag 
 

 
 
 
69 
• 
Place the bubble bag containing the collected samples and the blue ziplock bag containing the survey into 
the FedEx box. 
• 
  
 
 
STEP 14. 
 
• 
Ship the samples within 24 hours of stool collection. 
 
• 
See next page for shipping instructions. 
  
How to ship your samples: 
 
You may ship your package by FedEx using 
the instructions below OR you may return 
your package to the study clinic. Please do 
not drop off at a FedEx location. 
 
1) 
Call 1-800-GO-FEDEX (1-800-463-3339) to schedule a home pickup. 
 
2) 
The automated system will answer and ask what you’re calling about. Respond by saying: “Schedule a pick 
up.” 
 
3) 
Wait to hear all of the options and then press 0. 
 
4) 
After next options, press 0. 
 
5) 
Tell the representative: “I would like to schedule a pick-up for express shipment using a prepaid label.” 
 
6) 
The representative will ask you to provide your name, phone number, and address. This information is 
only for the FedEx pick-up service and will not appear anywhere on your study materials. 
 
7) 
The representative will ask you two questions, about the number and weight of your packages. 
a) 
The number of packages is one. 
b) 
The weight of the package is less than 5 pounds. 
 
8) 
The representative will arrange a time for pick-up with you. FedEx can pick-up a package from most 
locations, including your home or workplace. 
 
 
If you have any questions about the stool collection procedures, please do not hesitate to contact [field center 
staff name], at [field center phone number], or email [field center staff email address] 
 
Thank you for your participation in this study! 
 
 
 
Stool Receiving Protocol added 3/2/20 
 
1. Receive and sign for samples 

 
 
 
70 
2. Find Fedex receipt that matches tracking number and date both copies 
a. One copy will be turned in to Mike, the other kept with the sample 
3. Turn on UV light to sterilize biosafety cabinet 
4. Open box and remove samples and home survey 
5. Verify that the Home Survey ID and sample ID’s are the same 
6. Remove Fedex packing slip from front of the box 
7. Staple the Survey, Fedex Receipt, and packing slip together in that order 
8. Add ID, receipt date, sample QC metrics, and time of processing in LIMS 
9. Create participant ID labels using brady label maker for cryo tubes 
a. 6 labels for RNALater – Participant ID R 
b. 6 labels for 95% ethanol – Participant ID E9 
c. 
6 labels for 100% ethanol – Participant ID E10  
10. Label 18 cryo tubes with the labels on the side 
11. Clean Biosafety cabinet with ethanol after UV light is off and cabinet blower is on 
a. To cabinet add the following 
i. Biohazard waste bag 
ii. 2 P1000 pipets 
iii. P1000 tips 
iv. Chem wipes 
v. Solvents 
vi. Vortexer if necessary 
12. Vortex R sample well for 1 minute or longer if necessary to homogenize sample 
a. Pipet 1mL into first 4 tubes with R label 
b. Add 2mL of additional solvent to wash collection tube 
c. 
Vortex additional 10-20 seconds 
d. Pipet remaining 2-3mL of sample into last two tubes with R label – DO NOT FILL PAST ¾ MARK‼! 
13. Repeat with the two Ethanol tubes using 6 labeled cryo tubes per collection tube 
14. Samples to be stored in -80° C in Keyserling Stool Sample boxes. NRI freezers are equipped with 
temperature notification and back-up generators. 
15. Record locations of tubes in Keyserling Sample Sheet (Excel on NRI server) and LIMS 
16. Place hard copies (survey, FedEx, packing slip) in locked file cabinet (our floor is key-card access, and the 
lab door is also locked with restricted access) 
 
 
8.1.4:  Questionnaire data 
 
General protocol for collecting questionnaire data 
• 
See Section 5.5, Strategies for Recruitment and Retention, which outlines how eligibility and 
baseline questionnaires will be administered. 
• 
In brief, at the outset of the study, participants may decide to complete questionnaires on-line 
using the REDCap interface or by phone.  Whatever method they select for the baseline 
measures will be maintained throughout the remainder of the study. 
• 
The data collection windows are 4 weeks before baseline, 12 and 24 month follow-up. 
• 
The data collection window is 2 weeks before the 4 month follow-up visit (this is so the 
participant will have 2 weeks to make changes in behaviors after Counseling Session 4 before 
completing the questionnaire). 
 
Willett FFQ 

 
 
 
71 
• 
Because of the multiple response options on the Willett FFQ, which would be difficult to read 
aloud during a phone call, if a participant selects to complete questionnaires by phone, the 
Willett FFQ will be administered by research staff during the data collection visits (online, using 
REDCap). 
• 
The recall interval (look-back time frame) for the first administration of the Willett FFQ will be 
one year (standard look-back for this instrument).  
• 
To capture possible change in dietary intake in response to the intervention, the look back 
interval for subsequent administrations will be one month.   
 
Medication use 
• 
Our objective is to assess medication use and change in medication use for the following 
conditions. 
o Diabetes 
o High blood lipids 
o High blood pressure 
o Obesity (FDA approved weight loss medication) 
• 
Within 1 week of a measurement visit, the participant’s current medications will be printed for 
review at the visit. 
o At the visit, the list will be reviewed by the RA and medications associated with the 
above conditions will confirmed/updated. After the visit, the study medication REDCap 
form will completed by the RA. 
o If it is apparent that participant is unsure about medications and assistant from a 
clinician is needed to better determine medication use, Dr. Keyserling will be contacted 
to call the patient within 2 weeks of the visit to clarify medication use.  
 
Adverse outcomes 
• 
We do not anticipate adverse outcomes to be  a consequence of the intervention. 
• 
We will however assess for emergency room visits and hospitalizations at each follow-up 
questionnaire.  If the participant responds positive, then per our HIPAA authorization we will 
review the EHR to confirm primary reason for emergency room visit and/or admission.  
• 
We will categorize emergency room and hospitalizations as follows:  
o Acute myocardial infarction 
o Angina pectoris 
o Stroke 
 
Thrombotic 
 
Hemorrhagic 
o TIA 
o Heart failure 
o Coronary bypass surgery 
o Cancer 
 
Type of cancer 
o Broken bone 
 
Type of fracture 
o Light headedness or dizziness 
o Pneumonia 
o Other infection 
 
UTI 

 
 
 
72 
 
Other 
o Hypoglycemia 
o Other 
 
8.1.5: Study measures returned to participants 
 
Routine study measures that participants can interpret, will be returned to participants, including: 
• 
Weight 
• 
Height 
• 
BMI 
• 
Blood pressure 
• 
Blood lipids:  total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol 
• 
A1c 
 
8.1.6:  Study measures available to the participants primary care clinician (PCP) 
• 
The PCP will be notified about high blood pressure as outlined above in Section 8.1.3.2: above.   
• 
The lab report from LabCorp will be uploaded in the EHR.  The PCP is made aware of this upload. 
The lab report includes blood lipids (as above), A1c, and C-reactive protein (CRP) 
 
 
 
8.2. SAFETY ASSESSMENTS 
 
As noted, this study is considered minimal risk.  That said, the following safety procedures are included 
as part of this protocol.  
• 
Patients with advanced chronic kidney disease are at increased risk for high blood potassium 
levels.  This risk may be increased by a dietary pattern high in potassium, specifically a pattern 
with high fruit and vegetable intake, as advocated by our intervention. To reduce this risk, 
potential participants with advanced renal disease are excluded from this study, as follows: 
o As outlined in Section 5.5, participants screened for the study for whom we can 
calculate an eGFR based on a previously measured creatinine are excluded if the eGFR < 
30 mL/min/1.73 m2. 
o As outlined in Section 5.4, among participants referred to the study who have not had a 
creatinine and thus a calculated eGFR as part of their clinical care during the prior 2 
years, we will assess creatinine and eGFR as part of the baseline lab work and potential 
participants will be excluded if eGFR < 30 mL/min/1.73 m2. 
• 
As part of the physical activity intervention, an information sheet on safety while being active 
will be given to participants in the intervention group. 
• 
If a participant loses more than 35 pounds at the 4 month follow-up, 80 pounds at 12 month 
follow-up, or 100 pounds at 24 month follow-up, their study record and the EHR will be 
reviewed by Dr. Keyserling in conjunction with the participant’s PCP to determine if additional 
evaluation is warranted for underlying medical disease that may be contributing to weight loss.  
 
Addendum 7/25/21 to address high LDL cholesterol (> 190 mg/dL):  In addition to uploading LabCorp lab 
report to Epic with CC copy to PCP (which goes to the Epic in box folder “Media Manager”), will also 
send Epic staff message to PCP noting LDL >190 if no entry in the chart indicating high LDL already 

 
 
 
73 
addressed (most commonly this will be due to statin in tolerance).  Rationale for sending “staff 
message” is that this Epic inbox is likely to be reviewed more frequently than “Media Manager.” 
 
8.3  ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.3.1 DEFINITION OF ADVERSE EVENTS 
 
This protocol uses the definition of adverse event from 21 CFR 312.32 (a): any untoward medical 
occurrence associated with the use of an intervention in humans, whether or not considered intervention-
related. 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
 
For this study a serious adverse event includes, as outlined at:  https://www.hhs.gov/ohrp/regulations-
and-policy/guidance/reviewing-unanticipated-problems/index.html: 
 
1. results in death; 
2. is life-threatening (places the subject at immediate risk of death from the event as it occurred); 
3. results in inpatient hospitalization or prolongation of existing hospitalization; 
4. results in a persistent or significant disability/incapacity; 
5. results in a congenital anomaly/birth defect; or 
6. based upon appropriate medical judgment, may jeopardize the subject’s health and may require 
medical or surgical intervention to prevent one of the other outcomes listed in this definition 
(examples of such events include allergic bronchospasm requiring intensive treatment in the 
emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse) 
 
 
8.3.3  CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1  SEVERITY OF EVENT 
 
For adverse events (AEs) not included in the protocol defined grading system, the following guidelines will 
be used to describe severity.  
 

 
 
 
74 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
 
8.3.3.2  RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
All adverse events (AEs) will have their relationship to study procedures, including the intervention, 
assessed by an appropriately-trained clinician based on temporal relationship and his/her clinical 
judgment. The degree of certainty about causality will be graded using the categories below.  
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study procedures administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study procedures should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the study procedures, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal.  
• 
Potentially Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of study procedures). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study procedures administration makes a causal relationship improbable 
(e.g., the event did not occur within a reasonable time after administration of the study 
procedures) and in which other drugs or chemicals or underlying disease provides plausible 
explanations (e.g., the participant’s clinical condition, other concomitant treatments). 
• 
Not Related – The AE is completely independent of study procedures administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician. 
 
 
8.3.3.3  EXPECTEDNESS  
 

 
 
 
75 
Drs. Keyserling and Berkowitz will be responsible for determining whether an adverse event (AE) is 
expected or unexpected. An AE will be considered unexpected if the nature, severity, or frequency of 
the event is not consistent with the risk information previously described for the study procedures. 
 
8.3.4  TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
Solicited potential adverse events will occur at each follow-up measurement visit (4, 12, and 24 
months).  They include the following and we will ask if evaluation for these events included emergency 
room visit or overnight hospital stay.  
• 
Acute myocardial infarction 
• 
Angina pectoris 
• 
Stroke 
o Thrombotic 
o Hemorrhagic 
• 
TIA 
• 
Heart failure 
• 
Coronary bypass surgery 
• 
Cancer 
o Type of cancer 
• 
Broken bone 
o Type of fracture 
• 
Light headedness or dizziness 
• 
Pneumonia 
• 
Other infection 
o UTI 
o Other 
• 
Hypoglycemia 
o Other 
 
As allowed by our HIPAA authorization, the EHR will be reviewed to confirm the above events and 
modify the date of occurrence if not accurately provided by the participant. For clinical events that were 
managed outside of facilities with EHR data available to investigators, we will request that participants 
sign a release of medical information so that pertinent medical records can be reviewed.  
 
Unsolicited adverse events (AE) or serious adverse events (SAE) may come to the attention of study staff 
during counseling visits, phone calls, or via other channels of communications. They will be  categorized 
as above and entered into the appropriate follow-up questionnaire at the time of occurrence.  
 
Information to be collected about AEs and SAEs includes event description, time of onset, study 
clinician’s assessment of severity, relationship to study procedures (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study will be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 

 
 
 
76 
Any medical or psychiatric condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. Documentation of onset and duration of each episode will be 
maintained for AEs characterized as intermittent. 
 
Study staff will record events with start dates occurring any time after informed consent is obtained until 
the last day of study participation.  
 
8.3.5  ADVERSE EVENT REPORTING  
 
Adverse events will be reported as follows: 
 
SAEs that include the following and are 1) definitely, 2) probably, or 3) potentially related to the study  
will be reported to the chair of the DSMC and IRB within 1 working day: 
• 
Results in death 
• 
Is life-threatening (places the subject at immediate risk of death from the event as it occurred) 
 
Other SAEs and AEs will be reported to the Chair of the DSMC (by the 15th of each month for the 
preceding month) and will be summarized for review at each meeting of the DSMC. 
 
Reports of adverse events to the UNC IRB will follow their policy as outlined below: 
1. Do not wait to submit a reportable event to the IRB until you have all the information about the 
event. Report the event promptly and follow-up with additional information as it becomes 
available. 
2. A UPIRSO (Unanticipated Problem Involving Risks to Subjects or Others) that is also a Serious 
Adverse Event must be reported ASAP, but no later than one (1) week from the time you 
become aware of the event. 
3. All other UPIRSOs must be reported ASAP, but no later than two (2) weeks from the time you 
become aware of the event. 
 
 
8.3.6  SERIOUS ADVERSE EVENT REPORTING  
 
As outlined above in Section 8.3.5 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
 

 
 
 
77 
Participants will be aware of events we consider AEs and SAEs as they will be reported to us by 
participants.  Given the low risk nature of this study, we do not anticipate reporting summary 
information on adverse events to participants. The only “incidental finding” from the lab work reported 
to patients and PCPs would be an unexpected elevation in CRP.  We will instruct the PCP to respond to 
this type of findings as they would see as appropriate. We do not consider elevations in blood lipids and 
A1c to be incidental as they likely reflect an underlying biologic process that PCPs are familiar with and 
able to respond to in an appropriate fashion.  
 
8.38  EVENTS OF SPECIAL INTEREST  
 
N/A. 
 
8.3.9  REPORTING OF PREGNANCY  
 
Pregnancy:  Study participants who become pregnant may continue to participate in the study with the 
understanding that weight loss goals will be suspended during pregnancy through 3 months postpartum. 
If a pregnant participant wishes to continue with counseling sessions during pregnancy, the focus on 
counseling will be on dietary quality.  The participant may resume full participation 3 months 
postpartum. Any data collected while the participant is pregnant will be censured and follow-up data 
will not be collected until the participant is 6 months postpartum. 
8.4  UNANTICIPATED PROBLEMS 
8.4.1  DEFINITION OF UNANTICIPATED PROBLEMS 
 
This protocol uses the definition of Unanticipated Problems as defined by the Office for Human Research 
Protections (OHRP).  OHRP considers unanticipated problems involving risks to participants or others to 
include, in general, any incident, experience, or outcome that meets all of the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
8.4.2 UNANTICIPATED PROBLEMS REPORTING  
 
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB) and to the DSMC. The UP report will include the following information: 

 
 
 
78 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number 
• 
A detailed description of the event, incident, experience, or outcome  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP 
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB and to the DSMC ASAP but 
no later than one week of when the investigator becoming aware of the event.  
• 
Any other UP will be reported to the IRB and to DSMC ASAP but not later than within 2 weeks  of 
the investigator becoming aware of the problem  
 
8.4.3  REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 
N/A. 
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
This randomized trial will compare the effects of a Mediterranean-style (Med-style) dietary pattern 
intervention to an augmented usual care control group in primary care clinics.  The objectives of this 
trial are: 
Primary Aim (efficacy):  Weight loss at 24 months.  Hypothesis: Mean weight loss in the intervention 
group will exceed that in augmented usual care by ≥ 4% of initial body weight (e.g., ≥ 5% intervention, 
~1% control). 
Secondary weight outcomes:  Assess difference between study groups in proportion losing ≥ 5% body 
weight and differences in mean weight loss and proportion losing ≥  5% across 3 pre-specified 
subgroups: 1) with vs. without diabetes; 2) females vs. males; and 3) Whites vs. African Americans. 
Secondary Aim 1—Physiologic and Lifestyle Outcomes:  Assess change in blood pressure, A1c, markers 
of inflammation, skin carotenoids, and self-reported dietary patterns by study group. 
Secondary Aim 2—Process and Psychosocial Factors:  Assess process variables (attendance, fidelity, and 
acceptability of the Med-style dietary intervention), and key behavioral and psychosocial variables, 
including self-regulation/monitoring skills, self-efficacy, motivation, and quality of life. 

 
 
 
79 
Secondary Aim 3--Economic Outcomes:  Assess implementation cost, and incremental cost-effectiveness 
of the intervention relative to control in terms of cost per percentage reduction in weight (i.e., kg lost) 
and cost per quality adjusted life years (QALYs) gained. 
 
9.2 
SAMPLE SIZE DETERMINATION 
 
Note:  the text below was written for an anticipated sample size of 350.  We now plan to enroll 360 
participants. 
 
For our primary outcome, percent change in weight at 24 months, we have calculated sample size based 
on a two-sided test of 
significance with α=0.05 
and the standard 
deviation (SD) of percent 
change in weight of 7.3% 
as observed in the Heart 
Health Lenoir Project74, 75. 
Table 4 illustrates sample 
size calculations (allowing 
for 20% attrition) for 
various differences in 
mean changes between 
study groups based on a 
1:1 randomization allocation ratio. This table also provides power calculations to detect differences in 
weight change compared to control separately for pre-specified subgroups (those with vs. without 
diabetes, female vs. male, and white vs. African American assuming no sub-group is less than 40% of the 
overall sample).  We expect the intervention to reduce weight by at least 5% and that average weight 
loss in the intervention group will exceed that in augmented usual care by at least 4% (we estimate 
weight loss in usual care of ≤ 1%). Our plan to enroll 350 participants provides excellent power for our 
primary outcome (>99%) and reasonable power (82%) within each of our pre-specified sub-groups. For a 
difference between groups as small as 3%, we still have robust power for our primary outcome. 
Although we do not anticipate major differences in weight loss between those in our pre-specified 
subgroups, we will test the potential for large 
differential effects between subgroups using 
interaction terms. However, under the 
assumptions described above, our power to 
detect realistic difference in effects of 2-3% 
between these subgroups will be limited (about 
20-40%). Also, for a difference in proportions of 
those losing ≥ 5% body weight as small as 15% 
(e.g., 15% control vs. 30% intervention), allowing 
for attrition, the proposed sample size provides 85% power. For several secondary outcomes, we 
present in Table 5 minimally detectable differences corresponding to effect size of 0.33 for the sample 
size of 360 with 20% attrition, 80% power, and α =0.05 
  
 
Table 4. Power Estimates for % Change in Weight at 24 Month Follow-up 
Assumed Mean % 
Change Difference 
Between Groups 
Total 
Sample 
Size 
Overall 
Power to 
Detect 
Difference 
Minimum Power within Each 
Subpopulation (Diabetes status, 
sex, and race) to Detect Specified 
Difference 
3 
300 
89% 
51% 
350 
93% 
58% 
400 
96% 
64% 
 
 
 
 
4 
300 
98.8% 
76% 
350 
99.5% 
82% 
400 
99.8% 
87% 
Table 5.  Secondary Outcomes (at 24 month) 
Secondary Outcomes 
SD of 
change 
Difference in 
mean changes 
(δ)
Systolic BP 
23.1 
7.6 
Diastolic BP 
11.1 
3.6 
A1c (%) 
0.4 
0.1 
CRP 
0.9 
0.3 
Dietary pattern assessed by 
0.3 
0.1 

 
 
 
80 
9.3 
POPULATIONS FOR ANALYSES 
 
Intention-to-Treat (ITT) Analysis Population (i.e., all randomized participants) 
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
 
This is covered in Section 9.4.2. 
 
Update 6/8/25:  Our analysis plan as submitted with this protocol is below.  Before we assessed study 
outcomes, we prepared a more detailed statistical analysis plan.  This is include in 9.4.3 below:  
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
 
The primary analysis will be conducted using the ITT Population and will be repeated secondarily using 
the Per Protocol Population. 
Percent change in body weight = (Follow-up weight – baseline weight)/baseline weight x 100. 
We will compare the longitudinal mean % change in body weight between groups using analysis of 
covariance (ANCOVA), conducted using a linear mixed model. A mixed model will allow for the inclusion 
of all observed follow-up data for all participants. The model will include fixed effects for group, follow-
up visit (4, 12, or 24 months), group-by-visit interactions, site, baseline weight, race/ethnicity, sex, and 
diabetes status. To account for within-participant correlation, the model will allow for correlated error 
terms using an unstructured covariance matrix. For the primary comparison, we will use an 
appropriately specified linear contrast of the model parameters to test for a treatment effect at 24-
months at the 5% significance level. Secondarily, we will compare the groups at other time points and 
will estimate effect sizes along with 95% confidence intervals for each comparison. Secondarily, we will 
expand the model by including appropriate interaction terms, one at a time, to examine the potential 
heterogeneity of intervention effect in sub-groups, including diagnosis (diabetes vs. no diabetes), 
race/ethnicity, sex, and by degree of baseline obesity (BMI > 40 vs. less). Interaction terms will be tested 
at the 5% significance level. 
We will use a longitudinal mixed effects logistic regression model to compare the groups for proportions 
losing > 5% body weight at each follow-up visit; estimates of odds ratios and 95% confidence intervals 
will be provided. This model will control for the same covariates specified for the primary model. 
Missing Data 
We will make every effort to prevent missing data and to minimize attrition, however some dropout is 
expected. We will record reasons for dropouts to formulate realistic assumptions about observations 
that are missing, and compare respondents and non-respondents for differences on values of non-
missing variables. We will conduct a series of sensitivity analyses using similar models to evaluate the 
robustness of conclusions drawn from the primary model to departures from MAR assumption by 
comparing the magnitude of the primary treatment contrast. Specifically, we will use 1) multiple 
imputation including auxiliary information about the missingness; 2) shared-parameter models for not 
missing at random analyses where one variable is the efficacy outcome and the second variable is time 
to dropout, linked by a set of latent variables that are assumed to influence both the outcome and the 

 
 
 
81 
time to dropout; (3) patterning-mixture model, with models for each pattern of missing ness (e.g., by 
study phase); and (4) worst-case imputation, with baseline carried forward for intervention participants 
and best observation carried forward for control participants. 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Analysis of Secondary Objectives (1-2) 
The ITT Population will be used in the primary analysis of all secondary outcomes. Similar ANCOVA 
methods to those described above will be used to compare groups on each of the secondary outcomes; 
for any outcome measured at baseline, the corresponding ANCOVA will control for baseline value in 
addition to the covariates noted above. Blood pressure will be averaged over three repeated 
measurements at each visit. Because they are of secondary interest, tests on secondary outcomes will 
each be conducted at the 5% significance level with no adjustments for multiple comparisons. All 
estimates of effect size will be accompanied by 95% confidence intervals. Data from all secondary 
outcomes will be presented regardless of extent of “significance”. 
Descriptive summaries of process data (attendance at intervention contacts, fidelity to intervention 
delivery, and acceptability of the Med-style dietary pattern) will be provided for participants randomized 
to Group 1 in the ITT Population. No inferential statistics (p-values or confidence intervals) will be 
presented. 
 
Analysis of Secondary Objective 3 (Economic Analysis)   
 
We plan to conduct both a budgetary impact assessment and a cost-effectiveness analysis. The 
budgetary impact assessment will quantify the total and per participant costs of intervention delivery 
from the health system perspective using an Activity Based Costing (ABC) approach and cost tracking 
forms that the health economist (Finkelstein)158-160 has developed and refined in past behavioral trials. 
Using this approach, all relevant labor, materials and supplies, contracted services, and other relevant 
costs required to deliver the interventions will be captured by key activities. This information will allow 
policy makers to identify the total and per capita fixed and variable costs of the intervention and to 
forecast required budgets, should the intervention expand beyond the trial phase. The non-sunk cost 
estimates will also feed into the cost-effectiveness analysis. 
  
The incremental cost-effectiveness analysis will follow the approach Dr. Finkelstein has employed in 
prior studies, including a manuscript on the cost-effectiveness of commercial weight loss programs.161, 
162 We will compute the incremental cost per kilogram of weight loss relative to control, and using the 
approach presented in Finkelstein and Kruger,161 the incremental cost per quality adjusted life year 
(QALY) gained. The numerator for this analysis will be the incremental program delivery costs of the 
intervention relative to control, minus any cost offsets based on differences in health services and 
medication use across arms. The denominator will be the incremental QALYs based on average 
differences in EQ5D146 scores across arms collected at each assessment point. These scores can be used 
to quantify net QALY differences during the intervention period. In the base case, we will assume that 
QALY benefits decay linearly to 0 by the end of the second year post cessation of the study. All out-year 
cost and QALY estimates will be discounted at 3.5% per annum.  
 
To test for the sensitivity of our incremental cost-effectiveness ratio (ICER) estimates to changes in key 
inputs, we will conduct one-way sensitivity analyses by (1) doubling or halving all key model inputs; and 

 
 
 
82 
(2) varying the duration of benefit decay post program cessation from 2 years in both base cases to 0, 1, 
and 3 years. We will also conduct probabilistic sensitivity analyses to assess the effect of uncertainty 
regarding all input parameters using appropriate distributions for all cost and QALY values. Using the 
results, we will produce cost-effectiveness acceptability curves that graphically present the probability 
that the intervention is cost-effective for a range of willingness to pay metrics that a decision maker may 
consider. Based on the results, we will discuss the extent to which the intervention is likely to be both 
affordable and cost-effective 
 
6/9/25:  Note:  a separate Statistical Analysis Plan was prepared for this study.  This will be submitted to 
clinicaltrials. gov and journals as a separate document.  
 
9.4.4 SAFETY ANALYSES 
 
Prior to analysis, any data-captured adverse events will be coded by the principal investigators. Each 
type of event (by seriousness, severity, relationship to study) will be descriptively summarized in 
frequency tables by group (including only a single occurrence of any distinct type of event for any 
participant). Number of CVD events, ER visits, and hospitalizations will also be descriptively summarized 
by group. No inferential statistics (p-values or confidence intervals) are planned for comparing safety 
data between groups. 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
 
We will summarize baseline data (i.e., pre-randomization data) for the ITT Population. Measures of 
central tendency and dispersion for continuous and certain discrete variables will include means, 
standard deviations, medians, minima, and maxima. Categorical data will be summarized with 
frequencies and percentages. Some continuous variables may also be grouped into categorical levels 
and evaluated in frequency tables. No inferential statistics (i.e., p-values and/or confidence intervals) for 
comparing data between groups will be presented. 
 
9.4.6 PLANNED INTERIM ANALYSES  
 
N/A. 
9.4.7 SUB-GROUP ANALYSES 
 
Our pre-specified sub-groups are diabetes, race, and sex. 
Our plan to enroll 360 participants provides excellent power for our primary outcome (>99%) and 
reasonable power (82%) within each of our pre-specified sub-groups. For a difference between groups 
as small as 3%, we still have robust power for our primary outcome. Although we do not anticipate 
major differences in weight loss between those in our pre-specified subgroups, we will test the potential 
for large differential effects between subgroups using interaction terms. However, under the 
assumptions described above, our power to detect realistic difference in effects of 2-3% between these 
subgroups will be limited (about 20-40%). Also, for a difference in proportions of those losing ≥ 5% body 
weight as small as 15% (e.g., 15% control vs. 30% intervention), allowing for attrition, the proposed 

 
 
 
83 
sample size provides 85% power. For several secondary outcomes, we present in Table 5 minimally 
detectable differences corresponding to effect size of 0.33 for the sample size of 360 with 20% attrition, 
80% power, and α=0.05 
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
N/A. 
 
9.4.9 EXPLORATORY ANALYSES 
 
N/A.  
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATION 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS  
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT/ASSENT 
AND 
OTHER 
INFORMATIONAL 
DOCUMENTS 
PROVIDED 
TO 
PARTICIPANTS 
 
 
Consent forms describing in detail the study intervention, study procedures, and risks will be given to the 
participant and written documentation of informed consent will be completed prior to starting the study 
intervention.  The following consent materials are submitted with this protocol:   
• 
Consent form 
• 
Consent form for stored specimens 
• 
HIPAA authorization 
• 
Note: these forms will be updated per modifications approved by the IRB 
 
Consent form dated 9/23/19 
 
University of North Carolina at Chapel Hill 
Consent to Participate in a Research Study 
Adult Participants  
 
Consent Form Version Date: March 2, 2019 
IRB Study # 19-1712 
Title of Study: Randomized Explanatory Trial of a Mediterranean Dietary Pattern Weight Loss 
Intervention for Primary Care Practice—also known as the DELISH (Delicious Eating for Life in 

 
 
 
84 
Southern Homes) Study 
Principal Investigator: Thomas Keyserling, MD, MPH 
Principal Investigator Department: Medicine-Internal Medicine 
Principal Investigator Phone number: (919) 445-6794 
Principal Investigator Email Address: thomas_keyserling@med.unc.edu 
Funding Source and/or Sponsor: NIH National Heart, Lung, and Blood Institute (NHLBI) 
 
Study Contact Telephone Number: 919-843-9563 
Study Contact Email: kiira_lyons@med.unc.edu 
 
 
SUMMARY 
Intensive weight loss programs (14 or more counseling sessions over 6 months) are 
recommended for patients with a body mass index (BMI) greater than 30, yet long-term weight 
loss is often modest and many prior weight loss programs have not focused on what we now 
know to be a healthy eating pattern.  This study will compare a new weight loss program that 
focuses on a healthy eating pattern (call Med-South) with WW™ (formally Weight Watchers™), 
an effective and widely available weight loss program. Those who take part will be randomly 
assigned (like flipping a coin) to either the new weight loss program or WW™.  Both programs 
will last for 2 years with measurement visits at the start of the study and at 4, 12, and 24 month 
follow-up.   
 
This is a low-risk study, as both weight loss programs follow current guidelines for such 
programs.  There may be minor pain from the blood draws at each measurement visit.  Intensive 
weight loss programs do involve many counseling visits so taking part does require a time 
commitment, as described below. We expect participants in both study groups will lose weight 
and consider this a benefit of taking part in the study.  
  
Introduction:   
We invite you to take part in this research project.  This form tells you about the project so you 
can decide if you want to join this study.  If you do, you can change your mind and withdraw at 
any time.  We think you will benefit from taking part in this study, but you may not, as the 
purpose of research studies is to gain new knowledge that may help others in the future.  There 
also may be risks to being in a research project and these are noted on this form. If you do not 
take part in this study or you start the study and then decide to stop taking part before it is done, 
your decision will not be a problem for your doctors or other health care providers. 
 
What is the purpose of this study? 
The purpose is to develop and test a new weight loss program that includes a major focus on a 
healthy dietary pattern.  A healthy dietary pattern includes eating more foods with high-quality 
fats (vegetable oils, nuts, seeds, fish) and high-quality carbohydrates (fruits, non-starchy 
vegetables, whole grains, and beans) and eating fewer foods with poor quality carbohydrates 
(sugar sweetened beverages, refined grains, and many processed foods).  The eating pattern we 
are testing is similar to a Mediterranean dietary pattern. We call this new weight loss program 

 
 
 
85 
the “Med-South Weight Loss Program” because it will be tested in the southern US. To learn if 
the Med-South Weight Loss Program is more effective than currently available weight loss 
programs, we will compare it to WW™ (formally Weight Watchers™). We have selected 
WW™ because it is an effective weight loss program that is widely available.  
 
You are being asked to be in this study because your Body Mass Index (BMI) was greater than 
30 (when last checked at the clinic) and your doctor approved for you to take part because he or 
she thinks you might benefit from losing weight.  
 
How many people will take part in this study? 
There will be about 360 people in this research study. 
 
How long will your part in this study last? 
About 2 years. 
 
What will happen if you take part in the study? 
Frist, we mailed you the study brochure and then study staff called to confirm that you are 
eligible and to see if you want to take part.  If so, we mailed or emailed you this consent form. 
Next, we will call to answer any questions about this form. After doing so, if you want to take 
part, we will give you instructions on how to sign this form electronically or you may sign it at 
your first study visit.  Then, we will discuss how to complete the study surveys before the first 
visit.   
 
You may fill out these surveys online or over the phone (study staff will call and ask you the 
questions). If you decide to complete them over the phone, we will mail you one survey to 
complete before you come in (the survey goes over what you eat).  If you do not want to 
complete this in advance, just bring it to the first visit and we will complete the form then.  We 
expect it to take about 1.5 hours to fill out all surveys that ask about your lifestyle behaviors (like 
eating and physical activity habits) and other questions about your health. (You do not need to 
complete them at one time.)  Once you’ve filled out the surveys, we will set up a time and date 
for your in-person enrollment visit. 
 
The enrollment visit, follow-up measurement visits, and in-person counseling visits will take 
place at the UNC Center for Health Promotion and Disease Prevention, 1700 Martin Luther 
King, Jr, Blvd., Chapel Hill, NC, which is located about 5 miles north of the UNC main campus. 
(We will send instructions on how to get to our office.)  We will ask you to fast for 9 hours and 
avoid caffeine for 30 minutes before the enrollment visit and the other measurement visits. We 
will schedule these visits in the morning unless you ask for a visit later in the day.  If you have 
not already signed the consent forms on line, we will start the first visit by having you sign the 
consent forms.  Then, we will check to see if all surveys have been filled out and complete any 
that may not have been done. Next, we will review your current medication listed in the UNC 
medical record and record medications you are taking for diabetes, high blood pressure, high 
cholesterol, and for heart burn or stomach ulcers.  Before moving on to the measures outlined 
below, we will invite you to empty your bladder (recommended before measuring blood 
pressure). 
 

 
 
 
86 
Next, we will ask you to put your finger in an instrument that checks skin carotenoid levels 
(which tell us about how much fruit and vegetables you eat or drink).  This test does not hurt and 
takes less than 3 minutes.  We will also check your weight, height, and blood pressure.  After 
that, we will collect a blood specimen (about 2 tablespoons). We will measure total cholesterol, 
HDL cholesterol, triglycerides, and A1c (a test of your blood glucose over the past 3 months). 
We will report the results of these test to you and your primary care clinician.  We will also do 
some special research blood tests to look at how what you eat impacts blood inflammatory 
markers.  If you agree, we will also store blood for future research.  
 
There is a great deal of scientific interest in how dietary patterns may change the bacteria that 
live in your intestines (the microbiome) and if these changes impact weight change. So that we 
can learn if your microbiome changes in response to the weight loss programs, we invite 
participants to submit stool samples.  This part of the study is voluntary.  If you agree to do so, 
we ask you to collect and return (by mail) a stool sample within 2 weeks of the enrollment visit. 
For follow-up measurement visits, we may send you the collection kit in advance of the visit. 
Study staff will go over the instructions for collecting these samples at your first visit. 
 
It will take about 30-45 minutes to complete the measures outlined above and to collect your 
blood sample. 
  
After we collect the blood sample, study staff will randomly assign you (like flipping a coin) to 
receive either the Med-South Weight Loss Program or WW™.  If you are assigned to the Med-
South Weight Loss Program, you will receive your first counseling session, which should take 
45-60 minutes. If assigned to WW™, we will give you instructions on how to get started with 
this program, which should take about 15-30 minutes.  If you bring your smart phone to the visit, 
we will help you download the WW™ App.  Also, whichever group you are in, you will be 
encouraged to do moderate physical activity, like brisk walking, which is recommended for all 
Americans. 
 
Please note, WW™ is a safe and effective program that is considered a standard for community-
based weight loss programs.  If you are randomized to this program, we encourage you to engage 
with the program and take full advantage of what it has to offer. We do not know if the new 
program we have developed is better than WW™.  That is what we hope to learn in this study.  If 
it turns out the Med-South Program is better, then components of the Med-South Program may 
be added to other weight loss programs in the future. 
 
Med-South Weight Loss Program 
Most weight loss programs offer weekly one-on-one or group counseling sessions for 16-20 
weeks.  The Med-South Weight Loss Program is different and is given in 3 phases.  The program 
begins with Phase I, a 4 month lifestyle phase that focuses on the “basics” of healthy eating 
rather than weight loss.  Over the next 8 months in Phase II, we focus on weight loss, followed 
by a year-long (Phase III) phase to help you maintain weight loss. In Phases I, the main 
counseling sessions are given monthly, followed by check-in phone calls 1-2 weeks later.  In 
Phase II, the main counseling sessions will occur weekly for 6-8 weeks, depending on your 
progress.  There are also check-in phone calls--the number will vary based on your progress. 

 
 
 
87 
During Phase III, there are 2 main visits and follow-up phone calls.  More details about these 
visits are in the table below.   
 
Some of your counseling visits will be face-to-face with your counselor and some by phone. 
Only one member of a family may join this study, but other family members are invited to take 
part in face-to-face and phone counseling sessions.  The face-to-face format will be required for a 
total of 5 visits – the first visit in each of the 3 phases (right after study measurements at 
enrollment and 4 and 12 months), 2 months after starting the weight loss program in Phase II, 
and mid-way during Phase III (about 18 months after starting the Program).  The other sessions 
may be done by phone or in-person.  During Phases II and III, when you come to our office for a 
face-to-face counseling session, we will also check your weight. 
 
During face-to-face sessions, you and the counselor will sit side-by-side and use a web-based 
program or the paper format to review educational materials, select dietary goals, and list first 
steps to reach these goals. If the phone format is used for major counseling sessions, you may 
view the educational content online or use your paper version.  The program also includes brief 
telephone calls to check on progress towards goals selected at previous sessions and provide 
support for lifestyle change. The number of phone calls you get will depend on if you are 
meeting your personal weight loss goals in Phase II or keeping the weight off in Phase III.  The 
table below has more information. 
 
Phases 
# Contacts 
Contact Length 
Estimated Total 
Contact Time 
Phase I 
• 8 total  
o 4 core sessions: the first 
must be in-person; choice of 
in-person or phone for all 
others 
o 4 follow-up phone calls  
 
• Core session = 45-60 
min. 
 
• Follow-up call = 15 min. 
4 - 5 hours 
Phase II 
• 14 core sessions: the first and 
a visit about 2 months later 
must be in-person; choice of 
in-person or phone for all 
others. 
• 6-12 follow-up phone calls  
• Core session (in-
person) = 45-60 min. 
• Core session (phone) = 
30-45 min. 
• Follow-up call = 20-30 
min. 
 
8.7 – 14 hours 
(core) 
 
4.7 – 9.5 hours 
(Follow-up) 
Phase III 
• 2 core sessions (both in-
person) 
• 12-24 follow-up phone calls (1-
2 per month) 
• Core session (in-
person) = 45-60 min. 
 
• Follow-up call = 15-20 
min. 
1.25 – 2 hours 
(Core) 
3 – 8 hours 
(Follow-up) 
2-Year Program 
TOTAL 
44 – 60 Contacts 
-- 
21.7 – 38.5 
hours 
 
If you agree, we may audio-record a few counseling sessions for quality improvement purposes 
(to check on how our counselors are doing and provide feedback on areas needing 

 
 
 
88 
improvement).  These recorded sessions will be kept as electronic files but without information 
that could be used to identify you (other than your voice).  
 
WW™ Weight Loss Program 
If you are randomized to WW™, you will have access to both the workshop and digital 
components of the WW™ Program for 2 years.  WW offers in-person coaching and 
community-based learning through weekly Workshops at WW™ Studios. The Workshop 
component allows for attending weekly group meeting at a WW™ studio (local WW™ office).   
 
The Digital component can be accessed using the WW™ website or a smart phone App. The 
digital tools available in the WW™ Digital program include food tracking (either manually or 
with bar code scanning), progress charts, lifestyle coaching with 24/7 chat with a WW Coach, 
ability to track activity (manually or by syncing a fitness tracking device), incentives for 
behavior change (WellnessWins), recipes, and even local restaurant recommendations using 
GPS. You will also have access to Connect, a digital community for WW™ members.  Study 
staff will provide basic instructions on how to use the WW™ digital resources. 
 
The WW™ Program uses “SmartPoints” assigned to foods based on energy content and 
nutritional value, allocating a certain number of points to users daily based on their starting 
weight, weight loss goals, age, and sex. You'll receive a personalized SmartPoints budget made 
up of Daily SmartPoints, plus some extra Weekly SmartPoints for those days when you need a 
“cushion.” 
 
It you are assigned to the WW™ Program, you get to decide how many workshops to attend and 
how often to use the digital program. You can decide to not attend the workshops and only use 
the phone App and/or website. 
 
Follow-up measurement visits 
About 4, 12, and 24 months after starting the study, we will ask you to return for follow-up 
measures, which will be like those collected at study enrollment. We will ask you to fill out 
surveys online or by phone before this visit. It will take about 1 to 1.5 hours to fill out the 
surveys and 30 minutes for the measurement visits. Please note that for us to understand if the 
Med-South Weight Loss Program is effective, we have to carefully measure many study 
outcomes.  Most of these outcomes are measured by questionnaire.  The amount of blood work 
drawn for measurement is similar to that taken at routine office visits when several tests are 
ordered (about 2 tablespoons at baseline and 12 months; and 1.5 tablespoons at 4 and 24 
months).  The stool test is optional.  As outlined below, we will compensate for your time spent 
on measurement at a rate of $20 to $30 dollars per hour. And we thank you in advance for your 
willingness to complete this very important part of the study.   
 
Will I be informed about the study’s findings? 
We will inform all who take part about the study’s findings.  If the Med-South Weight Loss 
Program results in greater weight loss, we will make the Med-South Program materials available 
to those who received the WW™ Program. 
 

 
 
 
89 
Should I take part in this study? 
Prior research indicates that for weight loss studies to be effective, they must offer an intensive 
intervention, defined as at least 14 sessions over a 6-month period.  That is why the Med-South 
Program includes many contacts and why WW™ suggests frequent contact with their program. 
So, you need to ask yourself if you are willing to make this type of commitment to a weight loss 
program.  If you are, we welcome you to this study!  We will do all we can to accommodate your 
schedule or any special needs you may have as you take part in the weight loss programs and 
return for measurement visits.  
 
What are the possible benefits from being in this study? 
We think you may benefit from being in this study by improving your lifestyle and losing 
weight.  However, you may not benefit from being in this study. 
 
What are the possible risks or discomforts involved from being in this study? 
The possible risks and discomforts from being in this study are few and are listed below. 
• We do not think there is risk to you from the dietary advice given as part of the Med-
South Program or WW™.   
• Eating less is a part of standard weight loss programs. If you do not eat enough, you 
could lose weight too fast.  By asking you to check your weight often, the weight loss 
programs in this study will let you know if and when you are losing weight too fast.  
• Although doing more physical activity is not the main focus, both weight loss programs 
will recommend you do moderate physical activity. Those who increase their level of 
physical activity may experience minor muscle pain (this is common, affecting more than 
50 in a 100 people), but this type of activity rarely (fewer than 1 in a 100) causes serious 
health problems such as chest pain or asthma.  
• For those with diabetes, losing weight and reducing carbohydrate in the diet can lead to 
lower blood sugar, including hypoglycemia. This has occurred in less than 1 in a 100 
people in our past studies. We will provide those with diabetes information on how to 
reduce the risk of low blood sugar.  
• For those with high blood pressure, losing weight can lead to lower blood pressure, which 
can cause dizziness and even falls.  Adverse outcomes related to low blood pressure are 
very rare in weight loss studies, occurring in less than 1 in a 100 people.  Typically, the 
blood pressure is lowered slowly with weight loss, allowing your doctor time to observe 
the lower blood pressure and reduce your blood pressure medicine.  
• A blood sample will be collected by trained staff.  The risk of minor pain is very common 
(in more than half of people). Bruising does not happen often (about 1-10 of every 100 
persons) and the risk of infection or fainting is rare (fewer than 1 in 100).    
• In all studies, there is a very slight chance of loss of privacy (that is, others may see your 
study information). As stated below, we will do all we can to make sure this does not 
happen. 
 
Also, there may be other risks we did not list here. You should report to the research team any 
problems that may be due to this study. 

 
 
 
90 
 
What if we learn about new findings or information during the study?  
You will be given any new information gained during the study that might affect the risk of 
taking part in this study. 
 
How will information about you be protected? 
Your study bloodwork for routine tests (cholesterol levels and A1c) will be stored with your 
name as this will be sent to a commercial lab for analysis (LabCorp).  These samples are 
typically thrown away 3 days after collection.  Your study surveys and bloodwork for the 
inflammatory markers will be stored with your study ID number and your first and last initial, 
but NOT with your name (we call this de-identified data).  No one other than study staff will be 
able to connect your name and study ID as we will follow standard procedures to protect the 
privacy of research data.  
 
We may use your de-identified data, as described above, in future research without additional 
consent.  However, in some cases, the Institutional Review Board (called IRB and described 
below) may require that you be re-contacted and asked for your consent to use your data in a 
specific research study. You have the right, at that future time, not to participate in any research 
study for which your consent is sought. 
 
Participants will not be identified in any report or publication about this study. Although every 
effort will be made to keep research records private, there may be times when federal or state law 
requires the disclosure of such records, including personal information.  This is very unlikely, 
but if disclosure is ever required, UNC-Chapel Hill will take steps allowable by law to protect 
the privacy of personal information.  In some cases, your information in this research study could 
be reviewed by agents of the University or research sponsors for purposes such as quality control 
or safety. 
 
By signing this informed consent document, you agree that some of the information generated by 
participating in this study and/or a copy of the consent form may be included in your medical 
record and that this information may be viewed by other physicians or caregivers who provide 
healthcare services to you. This will allow the doctors caring for you to know what tests you may 
be receiving as a part of the study and know how to take care of you if you have other health 
problems or needs during the study. 
 
What is a Certificate of Confidentiality?  
This research is covered by a Certificate of Confidentiality. With this Certificate, the researchers 
may not disclose or use information, documents or biospecimens that may identify you in any 
federal, state, or local civil, criminal, administrative, legislative, or other proceedings in the 
United States, for example, if there is a court subpoena, unless you have consented for this use.  
The Certificate cannot be used to refuse a request for information from personnel of a federal or 
state agency that is sponsoring the study for auditing or evaluation purposes. 
 
The Certificate of Confidentiality will not be used to prevent disclosure as required by federal, 
state, or local law, such as mandatory reporting requirements for child abuse or neglect, disabled 
adult abuse or neglect, communicable diseases, injuries caused by suspected criminal violence, 

 
 
 
91 
cancer diagnosis or benign brain or central nervous system tumors or other mandatory reporting 
requirement under applicable law. The Certificate of Confidentiality will not be used if 
disclosure is for other scientific research, as allowed by federal regulations protecting research 
subjects or for any purpose you have consented to in this informed consent document. 
 
What will happen if you are injured by this research? 
It is not likely that you will be injured by this research, but all research involves a chance of 
injury.  If a medical problem occurs, the researchers will help you get medical care, but costs for 
this care will be billed to you and/or your insurance company. The University of North Carolina 
at Chapel Hill has not set aside funds to pay you for injuries or medical care.  However, by 
signing this form, you do not give up any of your legal rights. 
 
What if you want to stop before your part in the study is complete? 
You can withdraw from this study at any time, without penalty.  The research team also has the 
right to stop your participation at any time. This could be because you have had an unexpected 
reaction, or did not follow instructions, or because the entire study has been stopped. 
 
Will you receive anything for being in this study and will it cost you anything to take part? 
You will receive the weight loss program and lab work free of charge.  You will receive $60 
payment for your time devoted to study measures at the start of the study and at 4, 12, and 24 
month follow-up. The payment rate is $20-30/hour.  If you complete all measurement visits, you 
will receive a total of $240. In addition, you will receive $30 reimbursement for each stool 
specimen you submit.  
 
We will calculate the one-way distance from your home address to our research office and will 
reimburse mileage for measurement visits as below.  Note, there is no reimbursement for mileage 
if you attend a WW™ workshop or if you come in for a Med-South Weight Loss Program 
counseling visit that does not include a measurement visit (measurement visits are: enrollment 
visit and 4, 12, and 24 month follow-up visits).  Parking is free.  All reimbursement will be by 
gift card. 
 
Mileage reimbursement rate: 
 Less than 10: $0 
 10-19 miles: $10 
 20-29 miles:  $20 
 30-39 miles  $30 
 40-49 miles 
$40 
 50-59 miles  $50 
 60 or more 
$60 

 
 
 
92 
Who is sponsoring this study? 
This study is funded by the National Heart, Lung, and Blood Institute (NHLBI).  This means the 
research team is being paid by NHLBI for doing the study.  The researchers do not have a 
financial interest in the final results of the study. 
 
What if you are a UNC employee? 
Taking part in this research is not a part of your University duties and refusing will not affect 
your job.  You will not be offered or receive any special job-related consideration if you take part 
in this research. 
 
What if you have questions about this study? 
You have the right to ask, and have answered, any questions you may have about this research. If 
you have questions about the study (including payments), complaints, concerns, or if a research-
related injury occurs, you should contact the researchers listed on the first page of this form. 
 
A description of this clinical trial will be available on www.clinicaltrials.gov, as required by U.S. 
Law. This website will not include information that can identify you. At most, the website will 
include a summary of the results. You can search this website at any time. 
 
What if you have questions about your rights as a research participant? 
All research on human volunteers is reviewed by a committee that works to protect your rights 
and welfare.  If you have questions or concerns about your rights as a research subject, or if you 
would like to obtain information or offer input, you may contact the Institutional Review Board 
at 919-966-3113 or by email to IRB_subjects@unc.edu. 
  
Participant’s Agreement: 
 
I have read the information provided above.  I have asked all the questions I have at this time.  I 
voluntarily agree to participate in this research study. 
 
I also agree to submit stool samples as part of my participation in this study.  
____ yes 
_____no  
  
 
______________________________________________________ 
Signature of Research Participant 
 
____________________ 
Date 
 
______________________________________________________ 
Printed Name of Research Participant 
  

 
 
 
93 
 
______________________________________________________ 
Signature of Research Team Member Obtaining Consent 
 
____________________ 
Date 
 
______________________________________________________ 
Printed Name of Research Team Member Obtaining Consent 
  
 
 
 
 
 
 
 
University of North Carolina at Chapel Hill 
Consent for Storing Biological Specimens With Identifying Information 
_______________________________________________________________________ 
Consent Form Version Date: 3-2-2020 
IRB Study # 19-1712 
Title of Study: Randomized Explanatory Trial of a Mediterranean Dietary Pattern Weight Loss 
Intervention for Primary Care Practice—also known as the DELISH (Delicious Eating for Life in 
Southern Homes) Study 
Principal Investigators: Thomas Keyserling, MD, MPH 
Principal Investigator Department: Medicine-Internal Medicine 
Principal Investigator Phone number: (919) 445-6794 
Principal Investigator Email Address: thomas_keyserling@med.unc.edu 
Funding Source and/or Sponsor: NIH National Heart, Lung, and Blood Institute (NHLBI) 
 
Study Contact Telephone Number: 919-843-9563 
Study Contact Email: kiira_lyons@med.unc.edu 
______________________________________________________________________________ 
CONCISE SUMMARY 
 
See study consent form for summary of the overall study.  This form provides information about 
stored specimens that may be collected as part of  this study.  Providing stored specimens for the 
study is optional.  As outlined in the study consent form, blood samples will be obtained at 
enrollment and at 4, 12, and 24 month follow-up.  If you agree to allow the researcher to store 
your blood specimens for future research, an additional tube of blood (about 2 teaspoons) will be 
collected at the enrollment visit and 12 month follow-up visit.  Research using your stored 

 
 
 
94 
specimens may help the researchers better understand how your body responded to the weight 
loss interventions.  This research will also allow us to understand if your response to the 
intervention is related to your genes.   
The following information about research related to use of stored specimens is covered in study 
consent form: 
• What are some general things you should know about research? 
• How will information about you be protected? 
• What is a Certificate of Confidentiality? 
• What will happen if you are injured by this research? 
• Who is sponsoring this research? 
• What if you have questions about this research? 
• What if you have questions about your rights as a research subject? 
 
What is the purpose of this specimen repository or "biobank?" 
Research with blood, tissue or body fluids (specimens) can help researchers understand how the 
human body works and help answer research questions about how the body responds to different 
weight loss programs. It is possible that this type of research my help researchers improve weight 
loss interventions and even develop new products, such as drugs.  This type of research includes 
genetic research. Sometimes researchers collect and store many specimens together and use them 
for different kinds of research, or share them with other scientists; this is called a specimen 
repository or "biobank." 
 
The purpose of this particular repository or biobank is to have specimens that may be used to 
better understand weight loss interventions. Future research done with these specimens may 
include genetics research. Information on genetics research, including risks, is provided in the 
next section.  
 
Information on genetics research and risks of this research 
As genes are so important to our health, it is very common now for research studies to include genetic tests as we 
may do with stored specimens collected for this study.  If done, the major focus of the genetics research would be to 
see if genes or groups of genes help us to better understand how you responded to the weight loss programs. If you 
give a blood sample for genetics research, it will become the property of the UNC Chapel Hill and the sample may 
be kept for years. If you decide you want to withdraw from the genetics part of this study, contact the researcher 
listed above. The primary risk of genetic research is loss of privacy and as noted on this form, we will take all 
routine steps to reduce this risk.  That said, it is important for you to be aware of the following:  
• 
A Federal law called the Genetic Information Nondiscrimination Act (GINA) generally makes it illegal for 
health insurance companies, group health plans, and most employers to discriminate against you based on 
your genetic information.  GINA does not protect you against genetic discrimination by companies that sell 
life insurance, disability insurance, or long-term care insurance.   
• The National Institutes of Health (NIH) has established a national database that will hold 
information from many individuals across the country, including medical information and 
genetic information.  If information about you is sent to this national database, it will not 
be identified (that is, no one can tell whose information it is).  This information may 
include sequencing your entire genome (all of your genes). Also, access to this 
information will be controlled and limited to other researchers. 
 

 
 
 
95 
Will you receive results from the genetics research? 
Most genetics research is not expected to yield new information that would be meaningful to 
share with you personally. There are no plans to re-contact you or other participants with 
information about research results.  The use of your samples may result in commercial profit. 
You will not be compensated for the use of your samples. 
 
In a few participants, however, we may find genetic variants that are not related to the purpose of 
this study, but that are related to other medical conditions. These variants are rare and we expect 
to find them in fewer than 5% of the people who take part in this study. 
• 
If you have one of these variants, it suggests that you have a serious medical condition 
that can be treated OR that you have a high risk for a future medical problem that can 
likely either be prevented or more successfully treated if doctors know about it ahead of 
time. 
• 
An example of one of these conditions is hereditary cancer predisposition.  If you have a 
condition like this, your doctor may recommend special screening to look for early 
cancers that would be more easily treated, or in some cases preventive surgery to reduce 
the risk of developing cancer. 
• 
If you have one of these variants, your children would be at risk to have inherited it from 
you.  In addition, it may have been inherited from one of your parents, and others in the 
family (siblings, aunts/uncles, cousins etc.) might also be at risk to have the variant.  
• 
In the event that your genetic analysis suggests you have one of these variants, we will 
ask you for a separate sample using a saliva kit so that the finding can be confirmed by 
the clinical laboratory and reported to you by a clinical Genetic Counselor. The results 
will be included on a clinical laboratory report and it will become part of your UNC 
medical record.  
• 
The genetics team may make health care recommendations for you and your family based 
upon the genomic sequencing results. These recommendations might include other clinic 
visits and evaluations for you and other relatives.  These evaluations can provide 
important information about their need for medical care. These other visits, tests, and 
evaluations are not part of this study and will not be paid for by the study.  
• 
The American College of Medical Genetics and Genomics recommends that, when 
genomic sequencing is done, these variants should be looked for, interpreted, and 
reported. 
 
How will the specimens be collected? 
At the baseline visit and at the 1 year visit, 10 ml (2 teaspoons) of blood will be collected.  
This will be done during the same blood draw as other study tests so this will NOT involve 
another needle stick. The specimen will be labelled with a study number only. 
 
What will happen to the specimens? 
The specimens will stored in a freezer on the campus of UNC-Chapel Hill.  The code linking the 
number of on the specimen to your identifying information will be stored on a password 
protected computer. Only study researchers will have access to the code linking the study 
number of the tube to your identifying information.  
    

 
 
 
96 
What are the possible benefits to you? 
Benefits to you are unlikely. However, as outlined above, if genetic variants are found that 
suggest you have a serious medical condition that can be treated OR that you have a high risk for 
a future medical problem that can likely either be prevented or more successfully treated if 
doctors know about it ahead of time, we will contact you with this information.  This information 
may be beneficial to your health.  
 
What are the possible risks or discomforts involved with the use of your specimens? 
As the blood will be drawn at the same time as the routine study blood (during the same “stick”) 
there are not additional risks associated with collecting this specimen.  
 
There is a risk of breach of confidentiality. If this research involves genetics, there is also a 
potential risk for some of your relatives and other members of your ethnic group, since they 
share some of your genetic makeup. 
 
Will researchers seek approval from you to do future studies involving the specimens? 
By signing this consent form, you are giving your permission for researchers to use your 
specimens as described above. Current and future research is overseen by a committee called the 
Institutional Review Board (IRB). The role of the IRB is to protect the rights and welfare of 
research participants. We may use de-identified data and/or specimens from this study in future 
research without additional consent.  However, in some cases, the IRB may require that you be 
re-contacted and asked for your consent to use your specimens in a specific research study. You 
have the right, at that future time, not to participate in any research study for which your consent 
is sought. Refusal to participate will not affect your medical care or result in loss of benefits to 
which you are entitled. 
 
What will happen if you are injured by this research? 
 
All research involves a chance that something bad might happen to you. This may include the 
risk of personal injury. In spite of all safety measures, you might develop a reaction or injury 
from having your specimen collected. If such problems occur, the researchers will help you get 
medical care, but any costs for the medical care will be billed to you and/or your insurance 
company. The University of North Carolina at Chapel Hill has not set aside funds to pay you for 
any such reactions or injuries, or for the related medical care. However, by signing this form, you 
do not give up any of your legal rights. 
 
Will you receive results from research involving your specimens? 
Most research with your specimens is not expected to yield new information that would be 
meaningful to share with you personally. There are no plans to re-contact you or other subjects 
with information about research results, except as outlined above.   
 
Can you withdraw the specimens from the research repository? 
If you decide that you no longer wish for the specimens to be stored, you should contact the 
researchers on the front page of this form. It is best to make your request in writing. 
 
Any analysis in progress at the time of your request or already performed prior to your request 

 
 
 
97 
being received by the researcher will continue to be used as part of the research study. Once the 
researchers have been notified, your remaining specimens would be destroyed. If you do not 
make such a request, the specimens may be stored forever. The researchers may choose to 
destroy the specimens at any time. 
 
Will there be any cost to you for storage of the specimens? 
There will be no cost to you for the storage and use of the specimens for research purposes. 
 
What if you have questions about your rights as a research subject? 
All research on human volunteers is reviewed by a committee that works to protect your rights 
and welfare. If you have questions or concerns about your rights as a research subject you may 
contact, anonymously if you wish, the Institutional Review Board at 919-966-3113 or by e-mail 
to IRB_ subjects@unc.edu. 
  
 
Subject's  Agreement  
I have read the information provided above.  I have asked all the questions I have at this time.  I 
voluntarily agree to participate.  I agree to my specimen(s) being stored with the identifying 
code(s). 
 
______________________________________________________ 
Signature of Research Subject 
 
____________________ 
Date 
 
______________________________________________________ 
Printed Name of Research Subject 
  
 
______________________________________________________ 
Signature of Research Team Member Obtaining Consent 
 
____________________ 
Date 
 
______________________________________________________ 
Printed Name of Research Team Member Obtaining Consent 
  
 
 
 
University of North Carolina at Chapel Hill  
 
HIPAA Authorization for Use and Disclosure of Health Information for Research Purposes 
 
IRB Study # 19-1712 

 
 
 
98 
Title of Study: Randomized Explanatory Trial of a Mediterranean Dietary Pattern Weight Loss 
Intervention for Primary Care Practice—also known as the DELISH (Delicious Eating for Life in 
Southern Homes) Study 
 
Principal Investigator: Thomas Keyserling, MD, MPH 
Mailing Address for UNC-Chapel Hill Department: CB:7110 5020b Old Clinic , CB 7110 , 
Chapel Hill, NC 27599 , USA 
 
This is a permission called a “HIPAA authorization.” It is required by the “Health Insurance 
Portability and Accountability Act of 1996” (known as “HIPAA”) in order for us to get 
information from your medical records or health insurance records to use in this research study. 
 
1. If you sign this HIPAA authorization form, you are giving your permission for the following 
people or groups to give the researchers certain information about you (described below): 
 
Any health care providers or health care professionals or health plans that have provided health 
services, treatment, or payment for you such as physicians, clinics, hospitals, home health 
agencies, diagnostics centers, laboratories, treatment or surgical centers, including but not 
limited to the UNC Health Care System and its members and affiliates (collectively, 
“UNCHCS”), health insurance plans, and government health agencies. 
 
2. If you sign this form, this is the health information about you that the people or groups listed 
in #1 may give to the researchers to use in this research study: 
 
Any information in your medical records that relates to your participation in this research. Our 
primary focus will be to review your medical records for changes in your medications, to see if 
you were admitted to the hospital or evaluated in the emergency room for heart attack or stroke, 
and if any adverse outcomes occur as a part of this research to learn about your health outcomes 
if evaluated by health professionals for this type of problem.  
 
3. The HIPAA protections that apply to your medical records will not apply to your information 
when it is in the research study records. Your information in the research study records may also 
be shared with, used by or seen by collaborating researchers, the sponsor of the research study, 
the sponsor’s representatives, and certain employees of the University of North Carolina at 
Chapel Hill or other affiliated entities conducting the research, or government agencies (like the 
FDA) if needed to oversee the research study. HIPAA rules do not usually apply to those people 
or groups. If any of these people or groups reviews your research record, they may also need to 
review portions of your original medical record relevant to the situation. The informed consent 
document describes the procedures in this research study that will be used to protect your 
personal information. You can also ask the researchers any questions about what they will do 
with your personal information and how they will protect your personal information in this 
research study. 
 
4. If you want to participate in this research study, you must sign this HIPAA authorization form 

 
 
 
99 
to allow the people or groups listed in #1on this form to give access to the information about you 
that is listed in #2. If you do not want to sign this HIPAA authorization form, you cannot 
participate in this research study. However, not signing the authorization form will not change 
your right to treatment, payment, enrollment or eligibility for medical services outside of this 
research study. 
 
5. This HIPAA authorization will not stop unless you stop it in writing. 
 
6. You have the right to stop this HIPAA authorization at any time. You must do that in writing. 
You may give your written stop of this HIPAA authorization directly to Principal Investigator or 
researcher or you may mail it to the department mailing address listed at the top of this form, or 
you may give it to one of the researchers in this study and tell the researcher to send it to any 
person or group the researcher has given a copy of this HIPAA authorization. Stopping this 
HIPAA authorization will not stop information sharing that has already happened. 
 
7. You will be given a copy of this signed HIPAA authorization. 
______________________________________________________
Signature of Research Subject 
____________________ 
Date 
______________________________________________________
Print Name of Research Subject 
  
 
6/8/24:  The Final version of consent documents are included below: 
 
Main consent:  3/4/22 
University of North Carolina at Chapel Hill 
Consent to Participate in a Research Study 
Adult Participants  
 
Consent Form Version Date: March 4, 2022 
IRB Study # 19-1712 
Title of Study: Randomized Explanatory Trial of a Mediterranean Dietary Pattern Weight Loss 
Intervention for Primary Care Practice—also known as the DELISH (Delicious Eating for Life in 
Southern Homes) Study 
Principal Investigator: Thomas Keyserling, MD, MPH 
Principal Investigator Department: Medicine-Internal Medicine 
Principal Investigator Phone number: (919) 966-6081 
Principal Investigator Email Address: thomas_keyserling@med.unc.edu 
Funding Source and/or Sponsor: NIH National Heart, Lung, and Blood Institute (NHLBI) 
 
Study Contact Telephone Number: 919-843-9563 
Study Contact Email: kiira_lyons@med.unc.edu or thomas_keyserling@med.unc.edu 

 
 
 
100 
 
 
SUMMARY 
Intensive weight loss programs (14 or more counseling sessions over 6 months) are 
recommended for patients with a body mass index (BMI) greater than 30, yet long-term weight 
loss is often modest and many prior weight loss programs have not focused on what we now 
know to be a healthy eating pattern.  This study will compare a new weight loss program that 
focuses on a healthy eating pattern (call Med-South) with WW™ (formally Weight Watchers™), 
an effective and widely available weight loss program. Those who take part will be randomly 
assigned (like flipping a coin) to either the new weight loss program or WW™.  Both programs 
will last for 2 years with measurement visits at the start of the study and at 4-, 12-, and 24-month 
follow-up.   
 
This is a low-risk study, as both weight loss programs follow current guidelines for such 
programs.  There may be minor pain from the blood draws at each measurement visit.  Intensive 
weight loss programs do involve many counseling visits so taking part does require a time 
commitment, as described below. We expect participants in both study groups will lose weight 
and consider this a benefit of taking part in the study.  
 
(Please also see pages entitled “Information about Participating in a Research Study during COVID-19.” Specific 
information related to COVID-19 and limitations on in-person counseling or group counseling are noted in italics 
below. This may change over time according to updates in guidelines about COVID-19.)  
 
Introduction:   
We invite you to take part in this research project.  This form tells you about the project so you 
can decide if you want to join this study.  If you do, you can change your mind and withdraw at 
any time.  We think you will benefit from taking part in this study, but you may not, as the 
purpose of research studies is to gain new knowledge that may help others in the future.  There 
also may be risks to being in a research project and these are noted on this form. If you do not 
take part in this study or you start the study and then decide to stop taking part before it is done, 
your decision will not be a problem for your doctors or other health care providers. 
 
What is the purpose of this study? 
The purpose is to develop and test a new weight loss program that includes a major focus on a 
healthy dietary pattern.  A healthy dietary pattern includes eating more foods with high-quality 
fats (vegetable oils, nuts, seeds, fish) and high-quality carbohydrates (fruits, non-starchy 
vegetables, whole grains, and beans) and eating fewer foods with poor quality carbohydrates 
(sugar sweetened beverages, refined grains, and many processed foods).  The eating pattern we 
are testing is similar to a Mediterranean dietary pattern. We call this new weight loss program 
the “Med-South Weight Loss Program” because it will be tested in the southern US. To learn if 
the Med-South Weight Loss Program is more effective than currently available weight loss 
programs, we will compare it to WW™ (formally Weight Watchers™). We have selected 
WW™ because it is an effective weight loss program that is widely available.  

 
 
 
101 
 
You are being asked to be in this study because your Body Mass Index (BMI) was greater than 
30 (when last checked at the clinic) and your doctor approved for you to take part because he or 
she thinks you might benefit from losing weight.  
 
How many people will take part in this study? 
There will be about 360 people in this research study. 
 
How long will your part in this study last? 
About 2 years. 
 
What will happen if you take part in the study? 
First, we mailed you the study brochure and then study staff called to confirm that you are 
eligible and to see if you want to take part.  If so, we mailed or emailed you this consent 
form. Next, we will call to answer any questions about this form. After doing so, if you want 
to take part, we will give you instructions on how to sign this form electronically or you 
may sign it at your first study visit (enrollment visit). Then, we will schedule the enrollment 
visit.  
 
Study surveys  are completed online before the enrollment visit. We will email you a link to 
access the surveys by smartphone, tablet, or computer. We expect it to take about 1.5 hours 
to fill out all surveys that ask about your lifestyle behaviors (like eating and physical 
activity habits) and other questions about your health. You do not need to complete them 
all at one time. You may re-access the surveys using the same link.   (We will call you 
within 24 hours before this and all study visits to review a symptom checklist related to 
COVID-19.) 
 
The enrollment visit, follow-up measurement visits, and in-person counseling visits will 
take place at the UNC Center for Health Promotion and Disease Prevention, 1700 Martin 
Luther King, Jr, Blvd., Chapel Hill, NC, which is located about 5 miles north of the UNC 
main campus. (We will send instructions on how to get to our office.)  We will ask you to 
fast for 9 hours and avoid caffeine for 30 minutes before the enrollment visit and the other 
measurement visits, but if you are unable to fast you may still participate. We will schedule 
these visits in the morning. At the beginning of the visit, we will invite you to empty your 
bladder (recommended before measuring blood pressure). If you have not already signed 
the consent forms online, we will start the first visit by having you sign the consent forms.  
Then, we will check to see if all surveys have been filled out and complete any that may not 
have been done. Next, we will review your current medication listed in the UNC medical 
record and record medications you are taking for diabetes, high blood pressure, high 
cholesterol, and for heart burn or stomach ulcers.   
 
Next, we will check your weight, height, and blood pressure. Then, we will ask you to put 
your finger in an instrument that checks skin carotenoid levels (which tell us about how 
much fruit and vegetables you eat or drink).  This test does not hurt and takes less than 3 
minutes. After that, we will collect a blood specimen (about 2 tablespoons). We will 
measure total cholesterol, HDL cholesterol, triglycerides, and A1c (a test of your blood 

 
 
 
102 
glucose over the past 3 months). We will report the results of these tests to you and your 
primary care clinician.  We will also do some special research blood tests to look at how 
what you eat impacts blood inflammatory markers.  If you agree, we will also store blood 
for future research. (Please note:  on occasion, a study phlebotomist [person who draws 
blood samples] may not be at our research office. If this occurs, we may ask you to stop by 
one of the nearby UNC phlebotomy sites, at either the ACC or Eastowne clinics, to get your 
blood drawn prior to your visit at our research office. If this occurs, a study staff member 
will meet you at the phlebotomy office to answer any questions about the study and to have 
you sign the consent forms, if you did not already do so online. We will provide additional 
compensation for this extra time, as noted below.)  
 
There is a great deal of scientific interest in how dietary patterns may change the bacteria 
that live in your intestines (the microbiome) and if these changes impact weight change. So 
that we can learn if your microbiome changes in response to the weight loss programs, we 
invite participants to submit stool samples.  This part of the study is voluntary.  If you 
agree to do so, we ask you to collect and return (by mail) a stool sample within 2 weeks of 
the enrollment visit and the other study visits. Study staff will go over the instructions for 
collecting these samples at your first visit. 
 
It will take about 30-45 minutes to complete the measures outlined above and to collect 
your blood sample. 
  
After we collect the blood sample, study staff will randomly assign you (like flipping a coin) 
to receive either the Med-South Weight Loss Program or WW™.  If you are assigned to the 
Med-South Weight Loss Program, you will receive your first counseling session, which should 
take 45-60 minutes. If assigned to WW™, we will give you instructions on how to get started 
with this program, which should take about 15-30 minutes. (Note, these sessions will take place 
in a large conference room—you will be seated more than 10 feet away from study staff.) If you 
bring your smartphone to the visit, we will help you download the WW™ App.  Also, whichever 
group you are in, you will be encouraged to do moderate physical activity, like brisk walking, 
which is recommended for all Americans. 
 
Please note, WW™ is a safe and effective program that is considered a standard for community-
based weight loss programs.  If you are randomized to this program, we encourage you to engage 
with the program and take full advantage of what it has to offer. We do not know if the new 
program we have developed is better than WW™.  That is what we hope to learn in this study.  If 
it turns out the Med-South Program is better, then components of the Med-South Program may 
be added to other weight loss programs in the future. 
 
Med-South Weight Loss Program 
Most weight loss programs offer weekly one-on-one or group counseling sessions for 16-20 
weeks.  The Med-South Weight Loss Program is different and is given in 3 phases.  The program 
begins with Phase I, a 4-month lifestyle phase that focuses on the “basics” of healthy eating 
rather than weight loss.  Over the next 8 months in Phase II, we focus on weight loss, followed 
by a year-long (Phase III) phase to help you maintain weight loss. In Phases I, the main 
counseling sessions are given monthly, followed by check-in phone calls 1-2 weeks later.  In 

 
 
 
103 
Phase II, the main counseling sessions will occur weekly for the first 8 weeks, then monthly for 
the remaining 6 months, depending on your progress.  There are also check-in phone calls--the 
number will vary based on your progress. During Phase III, there are 2 main visits and follow-up 
phone calls.  More details about these visits are in the table below.   
 
Some of your counseling visits will be face-to-face with your counselor and some by phone. 
Only one member of a family may join this study, but other family members are invited to take 
part in face-to-face and phone counseling sessions.  (As of September 2020, due to COVID-19 
only one other family member or friend may come with you to in-person visits.) The face-to-face 
format will be required for a total of 5 visits – the first visit in each of the 3 phases (right after 
study measurements at enrollment, and 4 and 12 months), 2 months after starting the weight loss 
program in Phase II, and mid-way during Phase III (about 18 months after starting the Program).  
(As of September 2020, we will allow other visits to be done in person if that is the preference of 
the study participant.  Otherwise, the other visits will be done by phone or videoconferencing.)  
The other sessions may be done by phone/videoconference or in-person.  During Phases II and 
III, when you come to our office for a face-to-face counseling session, we will also check your 
weight.  
 
During face-to-face sessions, you and the counselor will use a web-based program or the paper 
format to review educational materials, select dietary goals, and list first steps to reach these 
goals. If the phone format is used for major counseling sessions, you may view the educational 
content online or use your paper version.  The program also includes brief telephone calls to 
check on progress towards goals selected at previous sessions and provide support for lifestyle 
change. The number of phone calls you get will depend on if you are meeting your personal 
weight loss goals in Phase II or keeping the weight off in Phase III.  The table below has more 
information. 
 
Phases 
# Contacts 
Contact Length 
Estimated Total 
Contact Time 
Phase I 
• 8 total  
o 4 core sessions: the first 
must be in-person; choice of 
in-person or phone for all 
others 
o 4 follow-up phone calls  
 
• Core session = 45-60 
min. 
 
• Follow-up call = 15 min. 
4 - 5 hours 
Phase II 
• 14 core sessions: the first and 
a visit about 2 months later 
must be in-person; choice of 
in-person or phone for all 
others. 
• 6-12 follow-up phone calls  
• Core session (in-
person) = 45-60 min. 
• Core session (phone) = 
30-45 min. 
• Follow-up call = 20-30 
min. 
 
8.7 – 14 hours 
(core) 
 
4.7 – 9.5 hours 
(Follow-up) 
Phase III 
• 2 core sessions (both in-
person) 
• Core session (in-
person) = 45-60 min. 
 
1.25 – 2 hours 
(Core) 
3 – 8 hours 
(Follow-up) 

 
 
 
104 
• 12-24 follow-up phone calls (1-
2 per month) 
• Follow-up call = 15-20 
min. 
2-Year Program 
TOTAL 
44 – 60 Contacts 
-- 
21.7 – 38.5 
hours 
 
If you agree, we may audio-record a few counseling sessions for quality improvement purposes 
(to check on how our counselors are doing and provide feedback on areas needing 
improvement).  These recorded sessions will be kept as electronic files but without information 
that could be used to identify you (other than your voice).  
 
WW™ Weight Loss Program 
If you are randomized to WW™, you will have access to both the workshop and digital 
components of the WW™ Program for 2 years.  WW offers in-person coaching and 
community-based learning through weekly Workshops at WW™ Studios. The Workshop 
component allows for attending weekly group meeting at a WW™ studio (local WW™ office). 
[As of September 2020, due to COVID-19, the workshop component will be available in a virtual 
videoconferencing [Zoom™] format in most locations, but may be available for in-person group 
sessions at some locations (where sessions are given in a large room with limited attendance and 
following North Carolina guidelines for wearing masks and social distancing.)] 
 
The Digital component can be accessed using the WW™ website or a smartphone App. The 
digital tools available in the WW™ Digital program include food tracking (either manually or 
with bar code scanning), progress charts, lifestyle coaching with 24/7 chat with a WW Coach, 
ability to track activity (manually or by syncing a fitness tracking device), incentives for 
behavior change (WellnessWins), recipes, and even local restaurant recommendations using 
GPS. You will also have access to Connect, a digital community for WW™ members.  Study 
staff will provide basic instructions on how to use the WW™ digital resources. 
 
The WW™ Program uses “SmartPoints” assigned to foods based on energy content and 
nutritional value, allocating a certain number of points to users daily based on their starting 
weight, weight loss goals, age, and sex. You'll receive a personalized SmartPoints budget made 
up of Daily SmartPoints, plus some extra Weekly SmartPoints for those days when you need a 
“cushion.” 
 
If you are assigned to the WW™ Program, you get to decide how many workshops to attend and 
how often to use the digital program. You can decide to not attend the workshops and only use 
the phone App and/or website. (As noted above, as of June 2020, due to COVID-19, the 
workshop component will be in a virtual videoconferencing [Zoom™] format, until further 
notice.) At the 4 month follow-up visit, we will check to see if you have been using the WW 
Program. If not, we will ask if you would like study staff to check in with you about using this 
Program. 
 
Follow-up measurement visits 

 
 
 
105 
About 4, 12, and 24 months after starting the study, we will ask you to return for follow-up 
measures, which will be like those collected at study enrollment. We will ask you to fill out 
surveys online before this visit. It will take about 1 to 1.5 hours to fill out the surveys and 30 
minutes for the measurement visits. Please note that for us to understand if the Med-South 
Weight Loss Program is effective, we must carefully measure many study outcomes.  Most of 
these outcomes are measured by questionnaire.  The amount of blood work drawn for 
measurement is like that taken at routine office visits when several tests are ordered (about 2 
tablespoons at baseline and 12 months; and 1.5 tablespoons at 4 and 24 months).  The stool test 
is optional.  As outlined below, we will compensate for your time spent on measurement at a rate 
of $20 to $30 dollars per hour. And we thank you in advance for your willingness to complete 
this very important part of the study.  (Please note:  on occasion, a study phlebotomist [person 
who draws blood samples] may not be at our research office. If this occurs, we may ask you 
to stop by one of the nearby UNC phlebotomy sites, at either the ACC or Eastowne clinics, 
to get your blood drawn prior to your visit at our research office. If this occurs, either 
study staff will meet you at the phlebotomy office or we will drop off the collection tubes in 
advance and ask you to bring them to the office. We will provide additional compensation 
for this extra time, as noted below.) 
 
Contacting you for follow-up visits 
We will call you up to 3 times over a 4-week period during regular work hours and after 
hours. We may also send up to 2 texts and/or emails if you agreed to receive texts or emails 
while taking part in this study. If we cannot reach you, we will send a letter and invite you 
to contact us if want to continue in the study or if you want to stop, to let us know why. 
Again, it is fine to stop taking part in this study at any time.  
 
 
Will I be informed about the study’s findings? 
We will inform all who take part about the study’s findings.  If the Med-South Weight Loss 
Program results in greater weight loss, we will make the Med-South Program materials available 
to those who received the WW™ Program. 
 
Should I take part in this study? 
Prior research indicates that for weight loss studies to be effective, they must offer an intensive 
intervention, defined as at least 14 sessions over a 6-month period.  That is why the Med-South 
Program includes many contacts and why WW™ suggests frequent contact with their program. 
So, you need to ask yourself if you are willing to make this type of commitment to a weight loss 
program.  If you are, we welcome you to this study!  We will do all we can to accommodate your 
schedule or any special needs you may have as you take part in the weight loss programs and 
return for measurement visits.  
 
What are the possible benefits from being in this study? 
We think you may benefit from being in this study by improving your lifestyle and losing 
weight.  However, you may not benefit from being in this study. 
 
What are the possible risks or discomforts involved from being in this study? 

 
 
 
106 
The possible risks and discomforts from being in this study are few and are listed below. 
• We do not think there is risk to you from the dietary advice given as part of the Med-
South Program or WW™.   
• Eating less is a part of standard weight loss programs. If you do not eat enough, you 
could lose weight too fast.  By asking you to check your weight often, the weight loss 
programs in this study will let you know if and when you are losing weight too fast.  
• Although doing more physical activity is not the main focus, both weight loss programs 
will recommend you do moderate physical activity. Those who increase their level of 
physical activity may experience minor muscle pain (this is common, affecting more than 
50 in a 100 people), but this type of activity rarely (fewer than 1 in a 100) causes serious 
health problems such as chest pain or asthma.  
• For those with diabetes, losing weight and reducing carbohydrate in the diet can lead to 
lower blood sugar, including hypoglycemia. This has occurred in less than 1 in a 100 
people in our past studies. We will provide those with diabetes information on how to 
reduce the risk of low blood sugar.  
• For those with high blood pressure, losing weight can lead to lower blood pressure, which 
can cause dizziness and even falls.  Adverse outcomes related to low blood pressure are 
very rare in weight loss studies, occurring in less than 1 in a 100 people.  Typically, the 
blood pressure is lowered slowly with weight loss, allowing your doctor time to observe 
the lower blood pressure and reduce your blood pressure medicine.  
• A blood sample will be collected by trained staff.  The risk of minor pain is very common 
(in more than half of people). Bruising does not happen often (about 1-10 of every 100 
persons) and the risk of infection or fainting is rare (fewer than 1 in 100).    
• In all studies, there is a very slight chance of loss of privacy (that is, others may see your 
study information). As stated below, we will do all we can to make sure this does not 
happen. 
 
Also, there may be other risks we did not list here. You should report to the research team any 
problems that may be due to this study. 
 
What if we learn about new findings or information during the study?  
You will be given any new information gained during the study that might affect the risk of 
taking part in this study. 
 
How will information about you be protected? 
Your study bloodwork for routine tests (cholesterol levels and A1c) will be stored with your 
name as this will be sent to a commercial lab for analysis (LabCorp).  These samples are 
typically thrown away 5-7 days after collection.  Your study surveys and bloodwork for the 
inflammatory markers will be stored with your study ID number and your first and last initial, 
but NOT with your name (we call this de-identified data).  No one other than study staff will be 
able to connect your name and study ID as we will follow standard procedures to protect the 
privacy of research data.  
 
We may use your de-identified data, as described above, in future research without additional 
consent.  However, in some cases, the Institutional Review Board (called IRB and described 

 
 
 
107 
below) may require that you be re-contacted and asked for your consent to use your data in a 
specific research study. You have the right, at that future time, not to participate in any research 
study for which your consent is sought. 
 
Participants will not be identified in any report or publication about this study. Although every 
effort will be made to keep research records private, there may be times when federal or state law 
requires the disclosure of such records, including personal information.  This is very unlikely, 
but if disclosure is ever required, UNC-Chapel Hill will take steps allowable by law to protect 
the privacy of personal information.  In some cases, your information in this research study could 
be reviewed by agents of the University or research sponsors for purposes such as quality control 
or safety. 
 
By signing this informed consent document, you agree that some of the information generated by 
participating in this study and/or a copy of the consent form may be included in your medical 
record and that this information may be viewed by other physicians or caregivers who provide 
healthcare services to you. This will allow the doctors caring for you to know what tests you may 
be receiving as a part of the study and know how to take care of you if you have other health 
problems or needs during the study. 
 
What is a Certificate of Confidentiality?  
This research is covered by a Certificate of Confidentiality. With this Certificate, the researchers 
may not disclose or use information, documents or biospecimens that may identify you in any 
federal, state, or local civil, criminal, administrative, legislative, or other proceedings in the 
United States, for example, if there is a court subpoena, unless you have consented for this use.  
The Certificate cannot be used to refuse a request for information from personnel of a federal or 
state agency that is sponsoring the study for auditing or evaluation purposes. 
 
The Certificate of Confidentiality will not be used to prevent disclosure as required by federal, 
state, or local law, such as mandatory reporting requirements for child abuse or neglect, disabled 
adult abuse or neglect, communicable diseases, injuries caused by suspected criminal violence, 
cancer diagnosis or benign brain or central nervous system tumors or other mandatory reporting 
requirement under applicable law. The Certificate of Confidentiality will not be used if 
disclosure is for other scientific research, as allowed by federal regulations protecting research 
subjects or for any purpose you have consented to in this informed consent document. 
 
What will happen if you are injured by this research? 
It is not likely that you will be injured by this research, but all research involves a chance of 
injury.  If a medical problem occurs, the researchers will help you get medical care, but costs for 
this care will be billed to you and/or your insurance company. The University of North Carolina 
at Chapel Hill has not set aside funds to pay you for injuries or medical care.  However, by 
signing this form, you do not give up any of your legal rights. 
 

 
 
 
108 
What if you want to stop before your part in the study is complete? 
You can withdraw from this study at any time, without penalty.  The research team also has the 
right to stop your participation at any time. This could be because you have had an unexpected 
reaction, or did not follow instructions, or because the entire study has been stopped. 
 
Will you receive anything for being in this study and will it cost you anything to take part? 
You will receive the weight loss program and lab work free of charge.  You will receive $60 
payment for your time devoted to study measures at the start of the study and at 4-, 12-, and 24-
month follow-up. The payment rate is $20-30/hour.  If you complete all measurement visits, you 
will receive a total of $240. In addition, you will receive $30 reimbursement for each stool 
specimen you submit and $20 reimbursement if we you have your blood work done at one of the 
UNC phlebotomy offices. 
 
We will calculate the one-way distance from your home address to our research office and will 
reimburse mileage for measurement visits as below.  Note, there is no reimbursement for mileage 
if you attend a WW™ workshop or if you come in for a Med-South Weight Loss Program 
counseling visit that does not include a measurement visit (measurement visits are: enrollment 
visit and 4-, 12-, and 24-month follow-up visits).  Parking is free.  All reimbursement will be by 
gift card. 
 
Mileage reimbursement rate: 
 Less than 10: $0 
 10-19 miles: $10 
 20-29 miles:  $20 
 30-39 miles  $30 
 40-49 miles 
$40 
 50-59 miles  $50 
 60 or more 
$60 
Who is sponsoring this study? 
This study is funded by the National Heart, Lung, and Blood Institute (NHLBI).  This means the 
research team is being paid by NHLBI for doing the study.  The researchers do not have a 
financial interest in the final results of the study. 
 
What if you are a UNC employee? 
Taking part in this research is not a part of your University duties and refusing will not affect 
your job.  You will not be offered or receive any special job-related consideration if you take part 
in this research. 
 
What if you have questions about this study? 
You have the right to ask, and have answered, any questions you may have about this research. If 
you have questions about the study (including payments), complaints, concerns, or if a research-

 
 
 
109 
related injury occurs, you should contact the researchers listed on the first page of this form. 
 
A description of this clinical trial will be available on www.clinicaltrials.gov, as required by U.S. 
Law. This website will not include information that can identify you. At most, the website will 
include a summary of the results. You can search this website at any time. 
 
What if you have questions about your rights as a research participant? 
All research on human volunteers is reviewed by a committee that works to protect your rights 
and welfare.  If you have questions or concerns about your rights as a research subject, or if you 
would like to obtain information or offer input, you may contact the Institutional Review Board 
at 919-966-3113 or by email to IRB_subjects@unc.edu. 
  
Participant’s Agreement: 
 
I have read the information provided above.  I have asked all the questions I have at this time.  I 
voluntarily agree to participate in this research study. 
 
I also agree to submit stool samples as part of my participation in this study.  
____ yes 
_____no  
  
 
______________________________________________________ 
Signature of Research Participant 
 
____________________ 
Date 
 
______________________________________________________ 
Printed Name of Research Participant 
  
 
______________________________________________________ 
Signature of Research Team Member Obtaining Consent 
 
____________________ 
Date 
 
______________________________________________________ 
Printed Name of Research Team Member Obtaining Consent 
  
 
Stored specimens updated 3-2-25 
 

 
 
 
110 
University of North Carolina at Chapel Hill 
Consent for Storing Biological Specimens With Identifying Information 
_______________________________________________________________________ 
Consent Form Version Date: 3-2-2020 
IRB Study # 19-1712 
Title of Study: Randomized Explanatory Trial of a Mediterranean Dietary Pattern Weight Loss 
Intervention for Primary Care Practice—also known as the DELISH (Delicious Eating for Life in 
Southern Homes) Study 
Principal Investigators: Thomas Keyserling, MD, MPH 
Principal Investigator Department: Medicine-Internal Medicine 
Principal Investigator Phone number: (919) 445-6794 
Principal Investigator Email Address: thomas_keyserling@med.unc.edu 
Funding Source and/or Sponsor: NIH National Heart, Lung, and Blood Institute (NHLBI) 
 
Study Contact Telephone Number: 919-843-9563 
Study Contact Email: kiira_lyons@med.unc.edu 
______________________________________________________________________________ 
CONCISE SUMMARY 
 
See study consent form for summary of the overall study.  This form provides information about 
stored specimens that may be collected as part of  this study.  Providing stored specimens for the 
study is optional.  As outlined in the study consent form, blood samples will be obtained at 
enrollment and at 4, 12, and 24 month follow-up.  If you agree to allow the researcher to store 
your blood specimens for future research, an additional tube of blood (about 2 teaspoons) will be 
collected at the enrollment visit and 12 month follow-up visit.  Research using your stored 
specimens may help the researchers better understand how your body responded to the weight 
loss interventions.  This research will also allow us to understand if your response to the 
intervention is related to your genes.   
The following information about research related to use of stored specimens is covered in study 
consent form: 
• What are some general things you should know about research? 
• How will information about you be protected? 
• What is a Certificate of Confidentiality? 
• What will happen if you are injured by this research? 
• Who is sponsoring this research? 
• What if you have questions about this research? 
• What if you have questions about your rights as a research subject? 
 
What is the purpose of this specimen repository or "biobank?" 
Research with blood, tissue or body fluids (specimens) can help researchers understand how the 
human body works and help answer research questions about how the body responds to different 
weight loss programs. It is possible that this type of research my help researchers improve weight 
loss interventions and even develop new products, such as drugs.  This type of research includes 
genetic research. Sometimes researchers collect and store many specimens together and use them 

 
 
 
111 
for different kinds of research, or share them with other scientists; this is called a specimen 
repository or "biobank." 
 
The purpose of this particular repository or biobank is to have specimens that may be used to 
better understand weight loss interventions. Future research done with these specimens may 
include genetics research. Information on genetics research, including risks, is provided in the 
next section.  
 
Information on genetics research and risks of this research 
As genes are so important to our health, it is very common now for research studies to include genetic tests as we 
may do with stored specimens collected for this study.  If done, the major focus of the genetics research would be to 
see if genes or groups of genes help us to better understand how you responded to the weight loss programs. If you 
give a blood sample for genetics research, it will become the property of the UNC Chapel Hill and the sample may 
be kept for years. If you decide you want to withdraw from the genetics part of this study, contact the researcher 
listed above. The primary risk of genetic research is loss of privacy and as noted on this form, we will take all 
routine steps to reduce this risk.  That said, it is important for you to be aware of the following:  
• 
A Federal law called the Genetic Information Nondiscrimination Act (GINA) generally makes it illegal for 
health insurance companies, group health plans, and most employers to discriminate against you based on 
your genetic information.  GINA does not protect you against genetic discrimination by companies that sell 
life insurance, disability insurance, or long-term care insurance.   
• The National Institutes of Health (NIH) has established a national database that will hold 
information from many individuals across the country, including medical information and 
genetic information.  If information about you is sent to this national database, it will not 
be identified (that is, no one can tell whose information it is).  This information may 
include sequencing your entire genome (all of your genes). Also, access to this 
information will be controlled and limited to other researchers. 
 
Will you receive results from the genetics research? 
Most genetics research is not expected to yield new information that would be meaningful to 
share with you personally. There are no plans to re-contact you or other participants with 
information about research results.  The use of your samples may result in commercial profit. 
You will not be compensated for the use of your samples. 
 
In a few participants, however, we may find genetic variants that are not related to the purpose of 
this study, but that are related to other medical conditions. These variants are rare and we expect 
to find them in fewer than 5% of the people who take part in this study. 
• 
If you have one of these variants, it suggests that you have a serious medical condition 
that can be treated OR that you have a high risk for a future medical problem that can 
likely either be prevented or more successfully treated if doctors know about it ahead of 
time. 
• 
An example of one of these conditions is hereditary cancer predisposition.  If you have a 
condition like this, your doctor may recommend special screening to look for early 
cancers that would be more easily treated, or in some cases preventive surgery to reduce 
the risk of developing cancer. 
• 
If you have one of these variants, your children would be at risk to have inherited it from 
you.  In addition, it may have been inherited from one of your parents, and others in the 
family (siblings, aunts/uncles, cousins etc.) might also be at risk to have the variant.  

 
 
 
112 
• 
In the event that your genetic analysis suggests you have one of these variants, we will 
ask you for a separate sample using a saliva kit so that the finding can be confirmed by 
the clinical laboratory and reported to you by a clinical Genetic Counselor. The results 
will be included on a clinical laboratory report and it will become part of your UNC 
medical record.  
• 
The genetics team may make health care recommendations for you and your family based 
upon the genomic sequencing results. These recommendations might include other clinic 
visits and evaluations for you and other relatives.  These evaluations can provide 
important information about their need for medical care. These other visits, tests, and 
evaluations are not part of this study and will not be paid for by the study.  
• 
The American College of Medical Genetics and Genomics recommends that, when 
genomic sequencing is done, these variants should be looked for, interpreted, and 
reported. 
 
How will the specimens be collected? 
At the baseline visit and at the 1 year visit, 10 ml (2 teaspoons) of blood will be collected.  
This will be done during the same blood draw as other study tests so this will NOT involve 
another needle stick. The specimen will be labelled with a study number only. 
 
What will happen to the specimens? 
The specimens will stored in a freezer on the campus of UNC-Chapel Hill.  The code linking the 
number of on the specimen to your identifying information will be stored on a password 
protected computer. Only study researchers will have access to the code linking the study 
number of the tube to your identifying information.  
    
What are the possible benefits to you? 
Benefits to you are unlikely. However, as outlined above, if genetic variants are found that 
suggest you have a serious medical condition that can be treated OR that you have a high risk for 
a future medical problem that can likely either be prevented or more successfully treated if 
doctors know about it ahead of time, we will contact you with this information.  This information 
may be beneficial to your health.  
 
What are the possible risks or discomforts involved with the use of your specimens? 
As the blood will be drawn at the same time as the routine study blood (during the same “stick”) 
there are not additional risks associated with collecting this specimen.  
 
There is a risk of breach of confidentiality. If this research involves genetics, there is also a 
potential risk for some of your relatives and other members of your ethnic group, since they 
share some of your genetic makeup. 
 
Will researchers seek approval from you to do future studies involving the specimens? 
By signing this consent form, you are giving your permission for researchers to use your 
specimens as described above. Current and future research is overseen by a committee called the 
Institutional Review Board (IRB). The role of the IRB is to protect the rights and welfare of 
research participants. We may use de-identified data and/or specimens from this study in future 
research without additional consent.  However, in some cases, the IRB may require that you be 

 
 
 
113 
re-contacted and asked for your consent to use your specimens in a specific research study. You 
have the right, at that future time, not to participate in any research study for which your consent 
is sought. Refusal to participate will not affect your medical care or result in loss of benefits to 
which you are entitled. 
 
What will happen if you are injured by this research? 
 
All research involves a chance that something bad might happen to you. This may include the 
risk of personal injury. In spite of all safety measures, you might develop a reaction or injury 
from having your specimen collected. If such problems occur, the researchers will help you get 
medical care, but any costs for the medical care will be billed to you and/or your insurance 
company. The University of North Carolina at Chapel Hill has not set aside funds to pay you for 
any such reactions or injuries, or for the related medical care. However, by signing this form, you 
do not give up any of your legal rights. 
 
Will you receive results from research involving your specimens? 
Most research with your specimens is not expected to yield new information that would be 
meaningful to share with you personally. There are no plans to re-contact you or other subjects 
with information about research results, except as outlined above.   
 
Can you withdraw the specimens from the research repository? 
If you decide that you no longer wish for the specimens to be stored, you should contact the 
researchers on the front page of this form. It is best to make your request in writing. 
 
Any analysis in progress at the time of your request or already performed prior to your request 
being received by the researcher will continue to be used as part of the research study. Once the 
researchers have been notified, your remaining specimens would be destroyed. If you do not 
make such a request, the specimens may be stored forever. The researchers may choose to 
destroy the specimens at any time. 
 
Will there be any cost to you for storage of the specimens? 
There will be no cost to you for the storage and use of the specimens for research purposes. 
 
What if you have questions about your rights as a research subject? 
All research on human volunteers is reviewed by a committee that works to protect your rights 
and welfare. If you have questions or concerns about your rights as a research subject you may 
contact, anonymously if you wish, the Institutional Review Board at 919-966-3113 or by e-mail 
to IRB_ subjects@unc.edu. 
  
 
Subject's  Agreement  
I have read the information provided above.  I have asked all the questions I have at this time.  I 
voluntarily agree to participate.  I agree to my specimen(s) being stored with the identifying 
code(s). 

 
 
 
114 
 
______________________________________________________ 
Signature of Research Subject 
 
____________________ 
Date 
 
______________________________________________________ 
Printed Name of Research Subject 
  
 
______________________________________________________ 
Signature of Research Team Member Obtaining Consent 
 
____________________ 
Date 
 
______________________________________________________ 
Printed Name of Research Team Member Obtaining Consent 
  
 
 
HIPAA Authorization updated 3/2/20 
University of North Carolina at Chapel Hill  
 
HIPAA Authorization for Use and Disclosure of Health Information for Research Purposes 
 
IRB Study # 19-1712 
Title of Study: Randomized Explanatory Trial of a Mediterranean Dietary Pattern Weight Loss 
Intervention for Primary Care Practice—also known as the DELISH (Delicious Eating for Life in 
Southern Homes) Study 
 
Principal Investigator: Thomas Keyserling, MD, MPH 
Mailing Address for UNC-Chapel Hill Department: CB:7110 5020b Old Clinic , CB 7110 , 
Chapel Hill, NC 27599 , USA 
 
This is a permission called a “HIPAA authorization.” It is required by the “Health Insurance 
Portability and Accountability Act of 1996” (known as “HIPAA”) in order for us to get 
information from your medical records or health insurance records to use in this research study. 
 
1. If you sign this HIPAA authorization form, you are giving your permission for the following 
people or groups to give the researchers certain information about you (described below): 
 
Any health care providers or health care professionals or health plans that have provided health 
services, treatment, or payment for you such as physicians, clinics, hospitals, home health 

 
 
 
115 
agencies, diagnostics centers, laboratories, treatment or surgical centers, including but not 
limited to the UNC Health Care System and its members and affiliates (collectively, 
“UNCHCS”), health insurance plans, and government health agencies. 
 
2. If you sign this form, this is the health information about you that the people or groups listed 
in #1 may give to the researchers to use in this research study: 
 
Any information in your medical records that relates to your participation in this research. Our 
primary focus will be to review your medical records for changes in your medications, to see if 
you were admitted to the hospital or evaluated in the emergency room for heart attack or stroke, 
and if any adverse outcomes occur as a part of this research to learn about your health outcomes 
if evaluated by health professionals for this type of problem.  
 
3. The HIPAA protections that apply to your medical records will not apply to your information 
when it is in the research study records. Your information in the research study records may also 
be shared with, used by or seen by collaborating researchers, the sponsor of the research study, 
the sponsor’s representatives, and certain employees of the University of North Carolina at 
Chapel Hill or other affiliated entities conducting the research, or government agencies (like the 
FDA) if needed to oversee the research study. HIPAA rules do not usually apply to those people 
or groups. If any of these people or groups reviews your research record, they may also need to 
review portions of your original medical record relevant to the situation. The informed consent 
document describes the procedures in this research study that will be used to protect your 
personal information. You can also ask the researchers any questions about what they will do 
with your personal information and how they will protect your personal information in this 
research study. 
 
4. If you want to participate in this research study, you must sign this HIPAA authorization form 
to allow the people or groups listed in #1on this form to give access to the information about you 
that is listed in #2. If you do not want to sign this HIPAA authorization form, you cannot 
participate in this research study. However, not signing the authorization form will not change 
your right to treatment, payment, enrollment or eligibility for medical services outside of this 
research study. 
 
5. This HIPAA authorization will not stop unless you stop it in writing. 
 
6. You have the right to stop this HIPAA authorization at any time. You must do that in writing. 
You may give your written stop of this HIPAA authorization directly to Principal Investigator or 
researcher or you may mail it to the department mailing address listed at the top of this form, or 
you may give it to one of the researchers in this study and tell the researcher to send it to any 
person or group the researcher has given a copy of this HIPAA authorization. Stopping this 
HIPAA authorization will not stop information sharing that has already happened. 
 
7. You will be given a copy of this signed HIPAA authorization. 
______________________________________________________
Signature of Research Subject 
____________________ 
Date 

 
 
 
116 
______________________________________________________
Print Name of Research Subject 
  
 
 
 
 
 
 
 
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Below also appears in Section 5.5.  We have received a waiver from the IRB to obtain verbal consent for 
the collection of questionnaire data from those who do not want to sign consent via the e-consent 
option. 
 
Step 6—Contacting participants identified in Step 5 to assess eligibility and interest (See PDF of this 
document)   
• 
Mail information brochure and cover letter to potential participants identified as outlined above 
and request that within one week, those who 1) know they are interested or 2) know that they 
are NOT interested send us an email or call to provide this information. Place those who express 
interest on our call list.   
• 
Approximately 10 days after mailing, start calling those who we do not hear from.  Our call 
protocol is as follows: 
o We will call up to 5 times over a 2 week period. We will attempt 2 calls during regular 
work hours (8:30 to 5:30 on weekdays) and 3 after hours, including Mon-Thurs evening 
between 5:31 and 9:00 pm and on Saturday calling between 8:30 and 5:30 pm.  
o We will leave up to 2 phone messages. 
• 
During eligibly calls, data are entered into the REDCap eligibility questionnaire. This form has 
text for the phone call.  
• 
If a potential participant is interested and eligible, staff will either mail or email the consent 
forms to this individual and an appointment will be made for the consent phone call in about 1 
week.  
Step 7—Study staff updates the Excel data base based on eligibility phone call.  
• 
Status variable 
o 1 indicates potential participant agrees to be contacted again for Consent Phone call.  
o 2 indicates potential participant contacted, but not interested.  Identifying data is 
removed. (Name, DOB, address, and phone #). 

 
 
 
117 
o 3 indicates potential participant contacted and is interested, but not eligible.  Identifying 
data is removed. (Name, DOB, address, and phone #). 
o 4 indicates potential participant never contacted by phone. Identifying data is removed. 
(Name, DOB, address, and phone #). 
Step 8—Consent phone call (See PDF of this document) 
• 
At this phone call, key components of the consent form are reviewed in detail to insure that the 
potential participant understands what participation entails.  During the phone call, the “Stored 
Specimens with Identifiers” and “HIPAA Authorization” are also reviewed. It the potential 
participant agrees to sign consent form via e-consent, instructions are given on how to do so. If 
the potential participant prefers to sign at the enrollment visit, then verbal consent to complete 
baseline questionnaires before the enrollment visit will be obtained, as approved by the IRB.   
• 
Instructions for completing baseline forms, on-line or by phone, are given and plans to complete 
these forms are made accordingly.  An appointment date is set for the baseline visit.  
• 
Parameters for contacting the patient are the same as for the eligibility phone call outlined in 
Step 6.  
  
Enrollment visit and randomization: At the enrollment visit, all questions will be answered about the 
study and those who did not sign the consent forms on-line will sign the consent form. Upon completion 
of baseline measures the participant will be ready for randomization. The research assistant will use a 
secure web-portal to ascertain randomization assignment 
 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
 
Given the low risk nature of the study, we do not anticipate stopping for adverse outcomes. 
 
The DSMC may stop the study based on their assessment of "futility" attributed to poor participant 
enrollment. 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, the safety and oversight monitor(s), and the sponsor(s) and funding agency. This confidentiality is 
extended to the data being collected as part of this study. Data that could be used to identify a specific 
study participant will be held in strict confidence within the research team. No personally-identifiable 
information from the study will be released to any unauthorized third party without prior written 
approval of the sponsor/funding agency.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor or funding agency, representatives 
of the Institutional Review Board (IRB), regulatory agencies or representatives from companies or 
organizations supplying the product, may inspect all documents and records required to be maintained 
by the investigator, including but not limited to, medical records (office, clinic, or hospital) and 

 
 
 
118 
pharmacy records for the participants in this study. The clinical study site will permit access to such 
records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor/funding agency 
requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at the <specify name of Data Coordinating Center>. This will not include 
the participant’s contact or identifying information. Rather, individual participants and their research 
data will be identified by a unique study identification number. The study data entry and study 
management systems used by this study will be secured and password protected. At the end of the 
study, all study databases will be de-identified and archived at the <specify name of Data Coordinating 
Center>. 
 
Measures Taken to Ensure Confidentiality of Data Shared per the NIH Data Sharing Policies  
It is NIH policy that the results and accomplishments of the activities that it funds should be made 
available to the public (see https://grants.nih.gov/policy/sharing.htm). The PI will ensure all mechanisms 
used to share data will include proper plans and safeguards for the protection of privacy, confidentiality, 
and security for data dissemination and reuse (e.g., all data will be thoroughly de-identified and will not 
be traceable to a specific study participant). Plans for archiving and long-term preservation of the data 
will be implemented, as appropriate.  
 
Certificate of Confidentiality  
To further protect the privacy of study participants, the Secretary, Health and Human Services (HHS), 
has issued a Certificate of Confidentiality (CoC) to all researchers engaged in biomedical, behavioral, 
clinical or other human subjects research funded wholly or in part by the federal 
government.  Recipients of NIH funding for human subjects research are required to protect identifiable 
research information from forced disclosure per the terms of the NIH Policy (see 
https://humansubjects.nih.gov/coc/index). As set forth in 45 CFR Part 75.303(a) and NIHGPS Chapter 
8.3, recipients conducting NIH-supported research covered by this Policy are required to establish and 
maintain effective internal controls (e.g., policies and procedures) that provide reasonable assurance 
that the award is managed in compliance with Federal statutes, regulations, and the terms and 
conditions of award. It is the NIH policy that investigators and others who have access to research 
records will not disclose identifying information except when the participant consents or in certain 
instances when federal, state, or local law or regulation requires disclosure. NIH expects investigators to 
inform research participants of the protections and the limits to protections provided by a Certificate 
issued by this Policy. 
 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
 
 
Most issues related to stored specimens are outlined on the Stored Specimen Consent Form in Section 
10.1.1.1.  Specifically, we will: 

 
 
 
119 
• 
Store specimens on the campus of the UNC-Chapel Hill.  Blood specimens will stored at -80 C in 
the lab of Steve Hursting, PhD, Gillings School of Global Public Health. 
• 
Data will be stored on secured servers administered by UNC-Chapel Hill IT. 
• 
At the time of this protocol preparation, data and specimens will be stored indefinitely.  
• 
Genetics testing may be done as outlined on the consent form. 
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Provide the name and contact information of the Principal Investigator and the Medical Monitor or 
Independent Safety Monitor. Update table heading to remove non-relevant role. 
Principal Investigator 
Medical Monitor or 
Independent Safety Monitor 
Thomas C. Keyserling, MD, MPH 
Professor of Medicine 
Department of Medicine 
Division of General Medicine and 
Clinical Epidemiology 
School of Medicine 
Adjunct Professor of Nutrition 
Gillings School of Global Public 
Health 
Wayne Rosamond, PhD 
Professor of Epidemiology 
Gillings School of Global Public 
Health 
UNC-Chapel Hill 
UNC-Chapel Hill  
Manning Drive 
Chapel Hill, NC 27599 
137 East Franklin Street, Suite 
306 
CB# 7435 
Chapel Hill, NC 2751 
 
919-445-6794 
919-962-3230 
jato@med.unc.edu 
wayne_rosamond@unc.edu 
 
This single site study has 2 primary committees 
• 
Operations Committee:  Includes MPIs, Project Director, and will RAs as appropriate.  Meets 
weekly. 
• 
Co-I Committee:  Includes co-investigators and meets as appropriate to discuss major study 
protocol issues and later to review and interpret the data. 
 
Oversight Committee 
• 
Data Safety Monitoring Committee:  Meets every 6 months while study is in the field.   
 
10.1.6 SAFETY OVERSIGHT 
 
Safety oversite is provided by a data safety monitoring committee.  The charter, dated 10/29/19 is below: 
 
DSMC Charter 

 
 
 
120 
October 29, 2019 
The investigators believe the interventions (Med-South Weight Loss Program and Augmented Usual 
Care, which is Weight Watchers) and measurement protocols pose minimal risk to participants. Because 
of this study’s low risk status, the data safety monitoring plan focuses on careful monitoring of the 
study’s progress as well as adverse events.  
The Data Safety Monitoring Committee (DSMC) will be comprised of: 
• 
The principal investigators:  Thomas C. Keyserling, MD, MPH and Carmen Samuel-Hodge, PhD, 
RD 
• 
The project director:  Kiira Lyons, MA 
• 
Study biostatistician:  Daniela Sotrez-Alvarez, DrPH 
• 
Three voting impartial members including one primary care clinician: 
o Wayne Rosamond, PhD, chair 
o Kimberly Truesdale, PhD 
o Katrina Donahue, MD, MPH 
Key personnel involved with the logistics of participant enrollment, participation, and follow-up will 
meet regularly (usually weekly) to review, among other things, progress on accrual, follow-up, and 
adverse events.  They will then prepare the following reports for the DSMC: 
 
Data Type 
Frequency of Review 
Subject accrual  
(including graphic of projected 
versus actual monthly 
enrollment) 
Weekly, with monthly summary reports for Chair of the DSMC. 
Adverse events 
These will be reported as they occur to the IRB with monthly 
reports to the Chair of the DSMC.  Any potentially study related 
death or severe and unexpected adverse event will be reported 
to the Chair of the DSMC within 1 working day. 
Adherence with treatment 
For the intervention group, study process measures will be 
collected by the web-based intervention program as well as 
monitoring checklists completed by the interventionist and 
audio recordings of up to 20% of sessions during the 2-year 
intervention. For the augmented usual care group, process 
measures will be assessed by questionnaire at follow-up 
measurement visits and through a data sharing agreement 
with Weight Watchers (WW). These data will be reviewed 
semi-annually at the DSMC meetings. 
Follow-up rates for data 
collection 
Weekly, with monthly summary reports prepared for the Chair 
of the DSMC. 

 
 
 
121 
(including the number of 
subjects eligible for and 
completing follow-up) 
Stopping rules with regard to 
benefit 
Not applicable, as intervention is designed to promote weight 
loss during a 24-month period and lifestyle change even 
without weight loss is likely beneficial.  
Stopping rules with regard to 
statistical power and adverse 
events 
Semi-annual assessment by DSMC. 
The DSMC will review subject accrual for futility and adverse 
events for compelling evidence of harm and will address 
appropriately.  
  
Operational definition of futility with regard to recruitment:  Less than one half of the anticipated 
sample size enrolled during the enrollment period.  This may be modified by the voting members of the 
DSMC. 
 
Meetings and responsibilities of the DSMC: Prior to enrollment, the DSMC will meet to review all 
protocols that may have a bearing on subject accrual or safety. The DSMC will subsequently meet every 
6 months until completion of the study. In addition, the PIs of the study or the Chair of the DSMC may 
convene additional meetings as needed. The primary role of the DSMC will be to monitor study data as 
outlined in the table above. The committee will also assist with any necessary modifications of protocols 
to address unexpected problems with subject accrual, subject attrition, or adverse events. 
 
Measurement and reporting of adverse events (AEs): The study team will monitor adverse events that 
include, but are not limited to the following:  deaths, hospitalizations, emergency room visits, 
hypoglycemia (defined as blood glucose < 60 mg/d with symptoms), and weight loss greater than 10 
pounds per month.  We will specifically inquire about these adverse events at all follow-up 
measurement visits and review medical records to confirm as appropriate (permission granted through 
HIPAA waiver).  The PIs will be responsible for completing an AE report when a reportable adverse event 
is recognized and will submit this report to the UNC IRB. The UNC IRB definitions, standards, and forms 
will be used for reporting AEs.  Also, at measurement visits, we will inquire about angina, myocardial 
infarction, transient ischemic attack, and stroke.   
Approval of study phases: The intervention will be delivered in 3 phases over 24 months by research 
staff: Phase I (4 months) focuses on adopting a Med-style dietary pattern; Phase II (8 months) on weight 
loss; and Phase III (12 months) on weight loss maintenance.  In our NIH application, we noted we would 
continue with intervention refinement until shortly before going to the field with each phase. This will 
allow us to keep up with the literature and be up-to-date at the outset of each phase.  Accordingly, we 
will seek IRB and DSMC approval for each Phase as outlined in the table below: 
Phase 
IRB Approval 
DSMC Approval 

 
 
 
122 
Phase 1 (first 4 months)  
10/2/19 
Nov, 2019 
Phase 2 (next 8 months)  
June, 2020 
June, 2020 
Phase 3 (next year) 
June, 2021 
June, 2021 
 
10.1.7 CLINICAL MONITORING 
 
N/A. 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Milestone:  Data Completeness and Quality Monitoring Reporting Plan 
Date:  1/27/20 
Version: 2.0 
--- 
 
This document outlines the data completeness and quality and monitoring plan for this study.  As 
outlined below, data will be stored in identified and de-identified data sets.  The overall data 
management plan has been approved by the UNC IRB and the study’s DSMC. 
 
The table below outlines sources of data, where it will be stored, and aspects of data management 
related to data quality and security.  The rows of the tables are organized by the chronological sequence 
of anticipated data acquisition. 
 
The primary data collection and management program with be REDCap as administered by the NC 
TraCS.  Links to relevant websites are provided below.   
• 
REDCap: https://tracs.unc.edu/index.php/services/informatics-and-data-science/redcap 
o REDCap includes software to collect confidential survey data via email link sent to 
participants.  In this study, data instruments used for data collection in this fashion are 
called “surveys.” 
o REDCap data collection instruments used only by research staff to collect study data are 
called “forms.” 
o All REDCap forms and surveys will include appropriate data entry ranges and skip 
patterns.  These forms and surveys will be thoroughly vetted during our REDCap 
“development” phase and before transitioning to “production” phase.  
• 
NC TraCS: https://tracs.unc.edu/ 
 
Correcting confirmed errors in the data. 
• 
The data manager and Dr. Keyserling will be responsible for making corrections. 
• 
A log of all corrections/edits will be maintained.  
 
The table includes the following columns: 
• 
Type and use of data:  indicates intended use of the data. 
• 
Data source:  indicates source of the data. 
• 
Data storage:  indicates where the data are stored.  All UNC servers noted below are password 
protected and adhere to security standards as outlined by the UNC IRB.  Abbreviations include:  
o NC TraCS:  UNC Translational and Clinical Sciences Institute. 

 
 
 
123 
o HPDP:  UNC Center for Health Promotion and Disease Prevention. 
o Sheps:  Cecil G. Sheps Center for Health Services Research. 
o CSCC:  UNC Collaborative Studies Coordinating Center. 
• 
Identified (Indt.):  indicates if identifiers are included with the data.   
• 
Data Review/Other Comments:  Outlines how the data will be reviewed and provides other 
comments as appropropriate.   Data collected by REDCap forms and surveys will be reviewed by 
the data manager or his designee, at a weekly (but no longer than 2 week) interval.  Incomplete 
data will be identified and reviewed by the Project Manager and/or MPIs to determine if 
additional effort should be directed towards collecting these data. If a major or key data 
component is missing, efforts will be made to collect this data in a timely fashion. For example, 
if a participant skips several pages on a survey, we will contact the participant to complete this 
survey.   
• 
Most data are collected at baseline and 4, 12, and 24 months follow-up.   
 
Type/Use of Data 
Data Source 
Data Storage 
Ident. Data Review/Other Comments 
Data from the 
electronic 
medical record 
NC TraCS 
data 
warehouse 
• NC TraCS 
server 
• HPDP server 
yes 
These data, extracted from the data 
warehouse utilized by NC TraCS, will 
be provided in an Excel format for 
each primary care clinician at  
participating study sites. The 
programming used to identify 
appropriate patients in the data 
warehouse will be tested at each 
practice against data prepared from 
the population feature of the 
electronic health record.  Output will 
be carefully inspected by research 
staff for completeness before it is 
sent to providers who must approve 
participation of their patients in this 
study. 
 
Data for 
providers to 
review regarding 
participation of 
their patients 
Primary 
care 
clinicians 
HPDP server 
yes 
Providers will either be sent a link to 
a password protected Excel file with a 
listing of their patients who meet 
basic study inclusion criteria.  They 
will be asked to review and note the 
patients who they refer to the study 
to receive an intensive multimodal 
weight loss program.  
 
Eligibility data 
From 
participants, 
collected by 
phone by 
research 
staff 
REDCap server 
yes 
Data review:  weekly, as outlined 
above.  

 
 
 
124 
 
Consent forms 
Participants  • For consent 
completed on-
line, REDCap 
server 
 
yes 
Research staff insure that consent 
documents are signed after all 
questions are answered. 
Participant study 
data collected 
using REDCap 
forms and 
surveys—
electronic 
questionnaires 
 
Participants 
REDCap server 
yes 
Surveys and forms will have PT-ID# 
and first and last initial.  Data will be 
collected via phone for those who do 
not want to complete online.  Data 
review:  weekly, as outlined above. 
Willett Food 
Frequency 
Questionnaire 
Participants 
• Data collected 
using REDcap 
version 
• At Harvard 
School of Public 
Health  
 
no 
Data sent to Harvard is de-identified. 
 
Anthropometrics, 
blood pressure, 
skin carotenoids 
Participants 
REDCap server 
yes 
Data entered by research field staff 
from instruments used for these 
assessments.  Note special protocol 
for primary outcome variable, body 
weight. Data review:  weekly, as 
outlined above. 
• For assessment at data collection 
time points, weight is assessed 2 
times.  If difference between 
weights is 1 pound or greater a 
third assessment is performed. 
For analysis, weights are 
averaged, using the 2 weights 
that differ by less than a pound. 
• For follow-up assessments, a 
second member of the research 
staff or clinical staff must observe 
data entry and initial that they 
have done so.  
 
“Clinical” blood 
work 
Participants 
• At LabCorp per 
storage of 
routine lab 
work.  
• REDCap 
 
yes  
Data review:  weekly, as outlined 
above.  This clinical lab results will be 
scanned in the electronic health 
record and except for CRP, results will 
be reported to participants.  
 

 
 
 
125 
Research blood 
work  
Participants 
• At Hursting lab 
• HPDP 
no 
Samples will be stored at Hursting 
Lab until all are collected.  Results will 
be entered into Excel spreadsheet 
and sent to HPDP. 
 
DNA analysis 
Participants 
-- 
no 
Blood for DNA analysis will be stored 
de-identified as part of this study for 
possible future analysis.  Samples will 
be stored at Hursting Lab. 
 
Process data 
collected use 
Web-based 
counseling 
program. 
 
Participants 
• Sheps server 
• HPDP 
 
yes 
Data collected by web-based 
counseling program.  These data will 
reside on the Sheps Center server 
until downloaded into a Excel file and 
sent to HPDP. 
Data sets for 
analysis 
Participants 
• REDCap 
• HPDP 
• CSCC 
yes 
and 
no 
Analysis datasets created from 
REDCap datasets.  Will be stored on 
Study’s Microsoft Team’s account.  
These dataset will have identifiers.  
De-identified REDCap data sets and 
other study datasets will be sent to 
CSCC for analysis.  
 
 
Intervention Fidelity — Consistent delivery of the study interventions will be monitored throughout the 
intervention phase of the study. Procedures for ensuring fidelity of intervention delivery are described in 
Section 6.2.1, Interventionist Training and Tracking.  
 
Protocol Deviations – The study team will review protocol deviations on an ongoing basis and will 
implement corrective actions when the quantity or nature of deviations are deemed to be at a level of 
concern according to the guidelines of the UNC IRB.  Protocol deviations will be reported to the UNC IRB 
as specified by the IRB guidelines, as outlined below: 
 
• 
Will the IRB still review study deviations? Yes. Study deviations will be reviewed as part of post-
approval monitoring by the IRB and/or the Clinical Trials Quality Assurance (CTQA) program. The 
IRB may also request your deviations records during its review of NSI. With this change, you will 
need to provide study deviation records at the request of the IRB. 
• 
How will I provide the deviation to the IRB for review? At the request of the IRB, you may 
provide the deviation log to the IRB outside of IRBIS. The procedure for providing the deviation 
log will be outlined at the time of the request.  
• 
Why are the changes being made? This new process is a way to meet regulatory requirements, 
focus resources on review of deviations involving increased risks to subjects, and reduce burden 
on IRB reviewers and investigators. 
• 
 Do I need to do anything? Aside from no longer providing deviation summaries at continuing 
review, you should be tracking study deviations as before. If you do not already have a deviation 
log for the study, we highly recommend you begin using the deviation log template provided 

 
 
 
126 
here: https://research.unc.edu/files/2018/06/ProtocolDeviation-Tracking-Log.docx.  If you 
choose to use a different form, be sure that the one you use includes all the same elements as 
found in the template. It is even more important now to familiarize yourself with SOP 1401, as 
failure to promptly report new safety information (NSI) could be considered serious or 
continuing noncompliance. 
 
Should independent monitoring become necessary, the PI will provide direct access to all trial related 
sites, source data/documents, and reports for the purpose of monitoring and auditing by the 
sponsor/funding agency, and inspection by local and regulatory authorities. 
 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
The data issues to be described in this section are covered in Section 10.1.8. 
 
10.1.9.2 STUDY RECORDS RETENTION  
 
Study data will be maintained for at least 10 years after final data collection. 
 
10.1.10 
PROTOCOL DEVIATIONS   
 
This study will follow the protocol deviation guidelines from the UNC IRB, as outlined below: 
 
Purpose: 
To record all protocol deviations that occur at a study site for both 
observational and interventional clinical research studies. 
IMPORTANT: This log is maintained in the Study Binder (Synonyms for this 
binder include Investigator Binder, Regulatory Binder, Investigator Site File 
[ISF], and Study File.) and should be made available upon request for 
review by the IRB and the Sponsor’s monitor. Deviations should be 
reported to the IRB of record as per the IRB Standard Operating 
Procedures. See OHRE/IRB SOP 1401 for reporting requirements for 
deviations to the UNC IRB.  
Audience/User: 
Study coordinators, principal investigators (PIs), other site staff, clinical 
monitor 

 
 
 
127 
Best Practice 
Recommendations: 
• Record protocol deviations in the tracking log as they occur, to ensure 
completeness and accuracy of the data.  
• The site PI should sign each form after it has been completed or 
immediately prior to a monitoring visit. If it has been signed with fewer 
than five deviations entered into it, the next identified deviation should 
be reported on a new page to ensure that all deviations have been 
reviewed by the PI. 
• Number each page and identify the final page of the log by indicating 
FINAL in the page number field. 
• Store pages in reverse chronological order, with the newest pages of the 
log placed at the front of the section. 
• Remove this page before using the log. 
  
 
*DEVIATION CATEGORIES: 
A. Informed Consent 
B. Eligibility 
C. Protocol implementation 
D. Reporting 
E. Other, specify in log 
**DEVIATION CODES: Numbers listed by the sample protocol deviations  
 
Informed Consent (Category A) 
1. Failure to obtain informed consent 
2. Consent form used was not current IRB-approved version 
3. Consent form does not include updates or information required by IRB 
4. Consent form missing 

 
 
 
128 
5. Consent form not signed and dated by participant 
6. Consent form does not contain all required signatures 
7. Other, specify in log 
 
Eligibility (Category B) 
8. Participant did not meet eligibility criterion 
9. Randomization of an ineligible participant 
10. Participant randomized prior to completing Baseline Assessment, etc. 
11. Randomization and/or treatment of participant prior to IRB approval of protocol 
12. Other, specify in log 
 
Protocol implementation (Category C) 
13. Failure to keep IRB approval up to date 
14. Participant receives wrong treatment 
15. Participant seen outside visit window 
16. Use of unallowable concomitant treatments 
17. Prescribed dosing outside protocol guidelines 
18. Missed assessment  
19. Laboratory tests not done 
20. Missed visit 
21. Other, specify in log 
 
Reporting (Category D) 
22. Not submitting reportable information to the IRB within 7 days 
23. Failure to respond to the NSI stipulations in the requested timeframe 
24. Other, specify in log 
 
Other (Category E) 
25. Other, specify in log 
 
IRB Study # 
   
Site 
Name/Nu
mber: 
   
Protocol Title 
(Abbreviated): 
   
Protocol 
ID/Numb
er: 
 

 
 
 
129 
Principal 
Investigator: 
   
Page 
number 
[1]: 
   
R
ef 
N
o. 
Subj
ect 
ID 
Date 
of 
Devia
tion 
Date 
Identi
fied 
Deviation Description 
Dev
. 
Typ
e 
[2] 
Res
ulte
d in 
AE? 
Did 
Subject 
Contin
ue in 
Study? 
Meets 
IRB 
Reporti
ng Req. 
(I.e. 
NSI) 
(Yes/N
o) 
IRB 
Report
ing 
Date 
1 
   
   
   
   
   
   
   
   
   
2 
   
   
   
   
   
   
   
   
   
3 
   
   
   
   
   
   
   
   
   
4 
   
   
   
   
   
   
   
   
   
5 
   
   
   
   
   
   
   
   
   
6 
   
   
   
   
   
   
   
   
   
7 
   
   
   
   
   
   
   
   
   
 
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY  
 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 

 
 
 
130 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-
reviewed journals.  Data from this study may be requested from other researchers 2 years after the 
completion of the primary endpoint by contacting the principle investigators.  Considerations for 
ensuring confidentiality of these shared data are described in Section 10.1.3. 
 
In addition, this study will comply with the NIH Genomic Data Sharing Policy, which applies to all NIH-
funded research that generates large-scale human or non-human genomic data, as well as the use of 
these data for subsequent research. Large-scale data include genome-wide association studies (GWAS), 
single nucleotide polymorphisms (SNP) arrays, and genome sequence, transcriptomic, epigenomic, and 
gene expression data. 
 
10.1.12 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial according to the 
guidelines set forth by the Conflict of Interest Program at UNC.  
 
10.2 ADDITIONAL CONSIDERATIONS 
 
N/A. 
 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
The list below includes abbreviations utilized in this template. However, this list should be customized for 
each protocol (i.e., abbreviations not used should be removed and new abbreviations used should be added 
to this list). Special terms are those terms used in a specific way in the protocol. For instance, if the protocol 
has therapist-participants and patient-participants, those terms could be included here for purposes of 
consistency and specificity.  
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 

 
 
 
131 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Council on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

 
 
 
132 
10.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
1.0 
2/12/20 
Initial Protocol Document 
This serves as the current 
protocol approximately 6 weeks 
before first participant is 
enrolled.  We anticipate an 
updated Version 1.1 to be 
submitted before enrollment of 
the first participant.  
1.1 
2/26/20 
Step 5, Section 5.5 updated 
Step 5 updated to allow 
enrollment goal of 40% for sub-
groups with fewer potential 
participants available for 
enrollment 
1.2  
2/28/20 
Stool protocol added 
To asses change in stool 
microbiome in response to the 
interventions.  This protocol 
was submitted to the UNC IRB 
on 3/2/20 and approved on 
3/12/10.  
1.3 
2/22/21 
Update protocol for Wave 2 
recruitment 
Wave 2 practices are smaller so 
will use cycle size of 60.  
1.4 
3/4/21 
Protocol for physician review of EHR 
added 
Protocol update.  
1.5. 
3/25/21 
Sec 8.1.3a.  Protocol amended to 
include time intervals for study 
activities after hospitalization:  Sec 
8.1.3a 
Self-explanatory 
1.6 
3/25/21 
Sec. 8.1.3.3 a. Phlebotomy protocol 
update intervals for collection study 
samples after randomization visit 
and collection of specimens at UNC 
labs.  
Self-explanatory 
1.7 
7/25/21 
Sec. 8.2. Decision made to send Epic 
staff message to PCP for LDL > 190 
and not otherwise addressed in the 
medical record.  
Self-explanatory 
1.8  
11/4/21 
Sec 5.2. HIV controlled defined as 
undetectable RNA and CD4 count 
above 400.  
Self-explanatory 
1.9 
6/8/25 
Entire protocol reviewed with minor 
edits to confer changes to protocol. 
Self-explanatory 

 
 
 
133 
Last IRB approved change to 
protocol was 5/11/23.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
134 
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