Obesity Risk in African American Women is Determined by a Diet-by-phenotype Interaction
Phase: NA
Conditions: Diet Modification
Sponsor: University of Alabama at Birmingham

Protocol (SPIRIT reporting guidelines) 
Administrative Information 
1. Title: Obesity risk in African American women is determined by a diet-by-phenotype 
interaction 
Trial acronym: CHAMPION (A Clinical Health Approach that Motivates Participation and 
Inspires Others through Nutrition) 
2a Trial Registration 
ClinicalTrials.gov ID NCT03499509 
2b Trial registration data set 
N/A 
3. Protocol Version  
Issue Date:  June 2019  
Authors: Catia Martins, Barbara Gower, Laura Lee Goree 
4. Funding 
1R01 DK115483-01A1 National Institutes of Health - National Institute of Diabetes and 
Digestive and Kidney Diseases (NIDDK).  
 
5a Roles and responsibilities: contributorship 
Authors contributions 
Barbara Gower conceived of the study and is the grant holder. Barbara Gower, Timothy Garvey, 
Kevin Fontaine, and Gareth Dutton initiated study design.  Barbara Gower, Timothy Garvey, 
Kevin Fontaine, Gareth Dutton, and David Bryan helped with implementation. Catia Martins and 

Barbara Gower prepared the statistical plan. All authors contributed to the refinement of the 
study protocol and approved the final version. 
5b Roles and responsibilities: sponsor contact information 
Trial Sponsor: National Institutes of Health - National Institute of Diabetes and Digestive and 
Kidney Diseases (NIDDK) 
Sponsor’s Reference: 
Contact Name: Padma Maruvada 
Telephone: 301-594-8884 
Email: maruvadp@mail.nih.gov 
5c Roles and responsibilities: sponsor and funder 
This funding source had no role in the design of this study and will not have any role during its 
execution, analyses, interpretation of the data, or decision to submit results. 
5d Roles and responsibilities: committees 
Principal investigators: Design and conduct of trial, preparations of protocol and revisions, 
publication of study reports, agreement of final protocol, reviewing progress of study and if 
necessary agreeing changes to the protocol to facilitate the smooth running of the study. Barbara 
Gower, Principal Investigator will oversee participant safety, study design, database integrity, 
and study conduct. 
Holly Wyatt, MD –Professor in the Department of Nutrition Sciences will be appointed as the 
Independent Safety Monitor to provide independent monitoring and review of the protocol every 
6 months.  
Introduction 
6a Background and rationale 

Introduction: The Scientific Premise of this study is that the high level of obesity displayed by 
African American (AA) women is due to their ability to secrete large amounts of insulin when 
high glycemic index foods are consumed.   
Mechanisms: When AA women eat a diet rich in starchy or sugary food (a “high-glycemic” diet 
that stimulates insulin secretion), the food that is eaten is stored as fat rather than being burned as 
fuel.   
Existing knowledge: AA women, as a group, are more obese than AA men or Caucasians of 
either sex.  We believe that this is due to the unique biology of AA women. Specifically, AA 
women secrete a lot of insulin when they eat sugary foods.   Because insulin promotes fat 
storage, this could make the food unavailable to burn as fuel and explain greater body fat in AA 
women. In fact, AA women have lower energy requirements than white women, and are more 
energetically efficient.  High insulin secretion, however, is only one factor that determines 
insulin action; another major factor is insulin sensitivity.  Our data have shown that over time, 
weight (fat) gain in obesity-prone AA women is higher in those who are more insulin sensitive, 
whereas “obesity-resistant” AA women have lower insulin sensitivity.  Our data also suggest that 
the fat-storing actions of insulin in AA women are worsened by a diet that promotes insulin 
secretion.  This diet is called a “high-glycemic diet.”  Finally, our data have shown that over time 
weight (fat) gain in AA women is predicted by the combination of insulin sensitivity and the 
amount of sugar and starch in the diet (called diet “glycemic load”).   
Need for a trial: We think that AA women will have an easier time losing weight if they eat a 
“low glycemic” diet.  In fact, we have seen in our research that AA women lose 50% more fat 
with low- vs high-glycemic diet.  This project will test this in a larger group of women, under 
controlled conditions.  We will also see if it is easier to keep the weight off with a low glycemic 

diet.  Additionally, we will determine if insulin sensitivity affects the weight loss response to diet 
composition. This study will test the effect of high and low glycemic diets for weight loss and 
weight-loss-maintenance in obese AA women.   
 
6b Background and rationale: choice of comparators 
Explanation for choice of comparators:  
We will be comparing a low glycemic diet versus a high glycemic diet. These diets were chosen 
based on our previous research mentioned above. 
 
7. Objectives 
Specific objectives or hypotheses 
1.1 Research hypothesis  
AA women with lower SI and/or higher AIRg will lose more FM when on low-CHO, versus low-
fat diet, and that this effect would be modulated by differences in EE (REE, TEE or ME). 
2. Study objectives 
To examine the independent and interactive effects of SI, AIRg, and diet with changes in fat 
mass (FM), resting (REE) and total energy expenditure (TEE), and mechanical efficiency (ME) 
in AA women with obesity during weight loss. 
 
2.1 Primary objective 
To examine the independent and interactive effects of SI, AIRg, and diet on changes in fat mass 
in African American women with obesity. 
2.2 Secondary objectives 
To characterize REE, TEE, and ME following low-CHO, versus low-fat diet. 

8. Trial design 
The CHAMPION study was designed as a two-arm randomized clinical trial. Randomization 
(1:1) was performed using a computer-generated randomization scheme prepared with PROC 
PLAN in SAS Ver. 9.4. 
 
Methods: Participants, interventions, and outcomes 
9. Study setting 
Data will be collected from healthy, but obese, AA women in the Birmingham, AL, metro area in 
The United States of America. Study testing will be performed in the Core facilities of the Center 
for Clinical and Translational Science (CCTS), Nutrition Obesity Research Center (NORC), and 
Diabetes Research Center (DRC) at UAB.  
10. Eligibility criteria: 
Participants will provide written, informed consent before the start of the study (see Appendix 1 
for sample Informed Consent Form). 
Inclusion criteria 
Participants eligible for the study must comply with all of the following at randomization: 
1. Age 19-65 years 
2. African American female 
3. BMI 30-45 kg/m2  
4. Sedentary to moderately active 
5. Normal menstrual cycle in premenopausal women 
6. Normal glucose tolerance based on HbA1c less than 6.0% 
Exclusion criteria 

1. History of eating disorder 
2. Daily use of tobacco (>1 pk/wk) 
3. Change in weight greater than 5 lb in the previous 3 months 
4. Presence of any condition (e.g. PCOS) or use of any medication (e.g., glucocorticoid) 
deemed by the project physician to interfere with study outcomes.   
11a Interventions: description 
Participants will be randomized to either low-fat or low-CHO hypocaloric diets for 10wks, 
followed by a 4-week weight stabilization period, with all food provided throughout. 
Energy requirements will be estimated by multiplying REE, measured with indirect calorimetry, 
by 1.5 (PA factor), and all participants will receive an individualized dietary prescription 
throughout the weight loss phase (60% of estimated energy needs or 40% energy deficit) and 
during the 4-week weight stabilization period (energy balance (EB)). During the weight stable 
phase, diets will be adjusted if weight is not stable. All the food for the duration of Phases 1 and 
2 was delivered to the participants’ homes on a weekly basis. The low-fat diet was aligned with 
the USDA guidelines (http://health.gov/dietaryguidelines/2015/guidelines/), and was comprised 
of 55% CHO, 20% fat, and 25% protein. The low-CHO diet was comprised of 25% CHO, 55% 
fat and 25% protein. Both diets emphasized complex over simple CHO, and allowed dairy 
products, fruits, and vegetables, within the CHO allowance of each diet.    
This will be followed by a 6-month weight maintenance phase with dietary prescription only, 
where participants will provide their own food. There will be monthly peer group support 
meetings with the dietitian to discuss nutrition education topics (such as food label reading, 
portion sizes, tips on eating out, etc). Participants will individually report their body weight to 
the dietitian and turn in an 8-day food record every month for 6 months. 

 
11b Interventions: modifications 
On 06/17/2020, the protocol was amended and approved by UAB IRB to minimize in person 
contact with participants due to COVID. DXA was replaced with an at home creatine dilution 
test to measure muscle mass. The post intervention (week 14) IVGTT and Mixed Meal 
Tolerance tests were omitted from the protocol. The Oral Glucose Tolerance Test at screening 
was replaced with measurement of Hemoglobin A1c finger stick (choice of at home or in 
person). Food was delivered to participants home via a commercial provider. The REE and 
Exercise tests were optional, if participants were not comfortable completing these in-person 
visits. Participants were given the option to complete the TEE visit at home or in-person. The 
weekly in-person meetings with the dietitian were moved to a Zoom or phone call and the 
monthly peer group meetings in Phase 3 were moved to Zoom. Food records were emailed 
and/or discussed via phone call, with food intake and body weight reported. 
 
11c Interventions: adherance 
Strategies used to improve adherence to intervention protocols included weekly phone calls with 
participants to report previous week’s specific food intake, report current body weight, and 
troubleshooting/support from a Registered Dietitian. Procedures for monitoring adherence 
include the measurement of respiratory quotient by indirect calorimetry, body weight and 
composition by bioelectrical Impedance Analysis and blood draw for the quantification of -
hydroxybutyrate, insulin, glucose, triglycerides, and cholesterol.  
 
 
11d Interventions: concomitant care 

Participants will be prohibited from participating in other weight loss programs (diet, exercise, 
and/or medications that induce weight loss). Participants will be instructed to continue their usual 
physical activity while in the study. 
 
12. Outcomes 
Main outcome measures: SI and AIRg will be measured at baseline with an intravenous glucose 
tolerance test, body composition with bioimpedance at baseline and Wk10. REE and body 
composition will also be measured at week 5. REE, TEE, and mechanical efficiency (ME) will 
be measured with indirect calorimetry, doubly labeled water, and a submaximal bike test, 
respectively, at baseline and Wk14. 
 
13. Participant timeline 
Participants were enrolled between June 2019 and August 2023. Participants will complete 10 
weeks of hypocaloric diet, 4 weeks of weight stabilization, and 6 months of weight loss 
maintenance. See figure 1. 

Fig. 1 Schematic diagram of the study design. 
 
14. Sample size 
This study was powered for differences in FM loss between the two diet groups. Our published 
data indicate that AA (both men and women) lose more FM when consuming a LG vs HG diet 
over 16 weeks  (1). Subgroup analysis within only the AA women (n=17), for only the 8-week 
hypocaloric phase, indicated that the women lost more FM with the LG diet [4.5  1.0 (SEM) 
kg] vs the HG diet [2.0 + 0.9 (SEM) kg] at a significance level of P=0.113. Based on these 
numbers, with 74 women (37/ group) we would have 80% power to detect a difference of 2.5 kg 
in FM loss between diets.   
15. Recruitment 
We will recruit from the local communities (UAB, city of Birmingham, and Jefferson and Shelby 
counties) via radio, newspaper, web-based advertisement, television advertisement, Research 
Match, UAB Reporter, word of mouth, and posting of flyers. 
 

Methods: Assignment of interventions 
16a Allocation: sequence generation 
After baseline testing, participants were randomized to one of two diets (low-glycemic, LG or 
high glycemic, HG) using a computer generated randomization scheme prepared with PROC 
PLAN in SAS Ver. 9.4.   
16b Allocation concealment mechanism 
Randomizations were placed in sealed sequentially numbered envelopes until interventions were 
assigned. All participants who give consent for participation, who fulfill the inclusion criteria, 
and complete baseline testing will be randomized. Participants will be enrolled by eligibility 
from the study team (principal investigator, coordinators, and dietitians). Study Coordinator will 
open sequentially numbered envelopes for diet intervention. The study dietitians will reveal the 
diet intervention to participants, along with a detailed diet introduction and explanation. 
17a Blinding (masking) 
No blinding. Since it was necessary to reveal the diet assignment to the study dietitian and the 
participant for appropriate diet introduction and education to the participant, this study will not 
involve blinding. 
17b Blinding (masking): emergency unblinding 
N/A  
Methods: Data collection, management, and analysis 
18a Data collection plan 
All measurements will be done in the Core facilities of the Center for Clinical and 
Translational Science (CCTS), Nutrition Obesity Research Center (NORC), and Diabetes 
Research Center (DRC) at UAB.  Participants will be instructed to avoid strenuous physical 

activity (PA) the day prior to testing, and all PA on the morning of testing. All SI tests will be 
performed in the Clinical Research Unit (CRU) at UAB’s CCTS after an overnight fast of 12 h. 
The following measurements will be performed at baseline and end of weeks 10 and 14, unless 
otherwise stated. 
SI will be assessed at baseline only using the intravenous glucose tolerance test (IVGTT) and 
minimal modeling, as previously described (2), but using 300 mg of glucose (20 % dextrose)/kg 
of body weight. AIRg will be calculated as the incremental insulin area-under-the-curve from 
minutes 0–10 following glucose injection using the trapezoidal method.  
Body composition (FM and fat-free mass) will be determined by bioimpedance analysis (BIA) 
(Seca 514 mBCA, Seca GmHb & Co. KG, Hamburg, Germany). 
Resting Energy Expenditure and substrate utilization will be determined in the 
CCTS/NORC/DRC Core Laboratory by indirect calorimetry (TrueOne 2400, Parvo Medics, 
Sandy, UT). Participants will be tested in the fasted (10h) condition following a 30-min supine 
rest at baseline and week 14.  
Total Energy Expenditure will be measured through the CCTS/NORC/DRC Core Laboratory by 
doubly-labeled water (DLW), at baseline and week 14, using a protocol based on established 
procedures (3). A FQ of 0.85 will be used at baseline to reflect a standard omnivorous diet, while 
at week 14, the FQ of the intervention diets will be used (4). FQ will be calculated using the 
equation of Black et al, FQ = (CHO% x 1.00) + (fat% x 0.71 ) + (protein% x 0.81) (4). 
 

Mechanical efficiency will be assessed using a submaximal cycling test, in the fasted state, at 
baseline and week 14. Following a familiarization period, participants cycled at 60 RPM at 10, 
20 and 50 watts of power in 4-minute increments. Ventilation, oxygen uptake, carbon dioxide 
production, respiratory exchange ratio, and heart rate were obtained throughout. Net skeletal 
muscle work efficiency will be expressed as the ratio of power generated (kcal/min) to the 
change in EE above REE (kcal/min) at each power output (5).      
Laboratory analyses. Blood samples will be collected in the fasting state and concentrations of 
glucose, βHB, total cholesterol, HDL-cholesterol and triglycerides measured using a SIRRUS 
analyzer (Stanbio, Boerne, TX), and insulin using a TOSOH A1A-900 immunoassay analyzer 
(TOSOH Bioscience, South San Francisco, CA) in the CCTS/DRC Core Laboratory. LDL-
cholesterol will be calculated using the Friedewald formula (6). 
 
18b Data collection plan: retention 
Participant retention will be promoted by weekly communications from the study dietitians and 
reminder communications from the study coordinators for upcoming in-person testing visits. 
 
19.  Data management 
Confidentiality will be maintained by coding all data with the subject’s identification number.  
Computerized data will be stored in the Department of Nutrition Sciences database.  Paper data 
will be stored in the Department of Nutrition Sciences in a locked room in a file cabinet. Only 
qualified research personnel will have access to the database containing the subject information.  
All subject data that are entered into statistical analyses and publication reports will refer to 
individuals only by number rather than name. 

All records pertaining to medical history, participation in this study, and data collected will be 
kept strictly confidential and will be recorded only by study number, to protect participant 
privacy.  Only study investigators and the UAB IRB will have access to this data. Information 
regarding participant demographics, body composition, metabolic outcomes, or blood outcome 
measures will be shared and labeled with the study number, a unique identifier, and the date of 
acquisition.  
 
20a Statistics: outcomes 
Statistical analysis will be performed with SPSS version 29 (SPSS Inc., Chicago, IL), and 
data presented as mean ± SD (or SEM). Statistical significance will be set at P < 0.05, unless 
otherwise specified, and normality of variables was assessed by visual inspection of histogram 
and Shapiro-Wilk test. Participants will be included in the analysis if they have SI data at 
baseline, and body composition at baseline and week 10. 
To test the hypothesis that AA women with obesity randomized to a low-CHO diet lose 
more FM than those randomized to a low-fat diet, we will analyze data from Phase 1 with 
generalized linear models (GLM). FM at week 10 will be the dependent variable, baseline FM, 
diet group, and SI (and/or AIR) the covariates. Finally, to test the hypothesis that SI (and/or) 
modulates the response to diet, a “diet x SI” interaction term will be added to the models; i.e., 
∆FM = β0 + β1 baseline FM + β2  baseline Si + β3 diet group + β4 diet group ∗ Si  + e1.   
To test the hypothesis that AA women with obesity randomized to a low-CHO diet 
maintain a higher TEE and REE, and a lower ME, than those randomized to a low-fat diet, we 
analyzed data from the end of Phase 2 with GLM.  TEE, REE, or ME (week 14) were the dependent 
variables; baseline TEE, REE, or ME, diet group, and SI (and/or AIRg) the covariates. For all 

outcomes, we tested for a phenotype-by-diet interaction by adding relevant interaction terms to the 
model; 
e.g., 
∆TEE (week 14 −baseline) = β0 + β1 baseline TEE + β2  baseline Si +
β3 diet group + β4 diet group ∗ Si  + e1.   
We will also test for menopausal status as potential predictors of the independent 
variables of interest, and include this variable in the models if necessary. The primary analyses 
will treat SI as a continuous variable and test for independent and interactive effects of SI and 
diet in statistical models. For sub-group analyses the median SI will be used to designate status: 
high vs low SI.  
 
20b Statistics: additional analyses 
N/A  
20c Statistics: analysis population and missing data 
N/A  
 
Methods: Monitoring 
21a Data monitoring: formal committee 
Holly Wyatt, MD –Professor in the Department of Nutrition Sciences is appointed as the 
Independent Safety Monitor to provide independent monitoring and review of the protocol every 
6 months.  
21b Data monitoring: interim analysis 
Description of interim analyses and stopping guidelines:   
22. Harms 
If an individual indicates discomfort or the desire to discontinue testing, tests will be terminated 
immediately. During routine visits and telephone calls, the study coordinator will query 

participants for any adverse events since their last contact with study personnel. In the case of an 
adverse event during times of testing, a study physician will be on call.  The physician will 
provide medical supervision for this study.  All adverse events will be reported to the UAB IRB 
and reviewed by the investigative team.  Should any of these individuals and/or the IRB identify 
that any adverse event may be related to the study protocol, testing will be suspended, and the 
protocol will be amended accordingly. 
23. Auditing 
A progress report will be submitted annually to the sponsor and to UAB IRB. 
Ethics and dissemination 
24. Research ethics approval 
The study is approved by UAB IRB (IRB-300001324) and annual progress reports will be sent to 
UAB IRB during the full duration of the study.   
25. Protocol amendments 
On 06/17/2020, the protocol was amended and approved by UAB IRB to minimize in person 
contact with participants due to COVID. DXA was replaced with an at home creatine dilution 
test to measure muscle mass. The post intervention (week 14) IVGTT and Mixed Meal 
Tolerance tests were omitted from the protocol. The Oral Glucose Tolerance Test at screening 
was replaced with measurement of Hemoglobin A1c finger stick (choice of at home or in 
person). Food was delivered to participants home via a commercial provider. The REE and 
Exercise tests were optional, if participants were not comfortable completing these in-person 
visits. Participants were given the option to complete the TEE visit at home or in-person. The 
weekly in-person meetings with the dietitian were moved to a Zoom or phone call and the 

monthly peer group meetings in Phase 3 were moved to Zoom. Food records were emailed 
and/or discussed via phone call, with food intake and body weight reported. 
 
26a Consent 
The study coordinator will obtain informed consent from trial participants. Potential participants 
who met the inclusion criteria for the study will be asked to review the consent form and if 
interested, to contact Study Coordinators.  If an individual is eligible to join the study, a 
screening measurement will be scheduled. During this visit, the project coordinator will review 
the consent form and obtain informed consent.  The consenting process is confidential, and will 
take place in a private room. 
26b Consent: ancillary studies 
N/A 
27. Confidentiality 
Confidentiality is maintained by coding all data with the subject’s identification number.  
Computerized data will be stored in the Department of Nutrition Sciences database.  Paper data 
will be stored in the Department of Nutrition Sciences in a locked room in a file cabinet. Only 
qualified research personnel have access to the database containing the subject information.  All 
subject data that are entered into statistical analyses and publication reports will refer to 
individuals only by number rather than name. 
All records pertaining to medical history, participation in this study, and data collected will be 
kept strictly confidential and will be recorded only by study number, to protect participant 
privacy.  Only study investigators and the UAB IRB will have access to this data. Information 
regarding participant demographics, body composition, metabolic outcomes, or blood outcome 

measures will be shared and labeled with the study number, a unique identifier, and the date of 
acquisition.  
28. Declaration of interests 
All study investigators and other personnel will complete conflict of interest disclosure training 
and forms. 
29. Data access 
Only those listed on the study protocol, as approved by UAB IRB will have access to study data. 
30. Ancillary and post trial care 
UAB and NIDDK will not provide any payment if participants are harmed as a result of taking 
part in this study. If such harm occurs, treatment will be provided. However, this treatment will 
not be provided free of charge. 
 
31a Dissemination policy: trial results 
Study investigators will report study analyses and results via publications. Participants will 
receive individual clinical test results after completion of the study. 
31b Dissemination policy: authorship 
Authorship eligibility guidelines and any intended use of professional writers 
 
31c Dissemination policy: reproducible research  
Plans, if any, for granting public access to the full protocol, participant-level dataset, and 
statistical code 
The protocol and results will be posted on Clinicaltrials.gov website. 
Appendices 

32. Informed consent materials 
33. Biological specimens 
DNA will be collected for admixture analysis and analysis of SNPs related to beta cell function.   
 
 
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