Decreasing Stress in Diabetes: A Randomized Controlled Trial
Phase: NA
Conditions: Stress, Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1
Sponsor: Milton S. Hershey Medical Center

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HRP-591 - Protocol for 
Human Subject Research
Protocol Title:
Decreasing Stress in Diabetes: A Randomized Controlled Trial (DE-STRESS)
Principal Investigator:
Name: Nazia Raja-Khan, MD 
Department: Medicine/Endocrinology
Telephone: (717) 531-8395
E-mail Address: nrajakhan@pennstatehealth.psu.edu
Version Date:
 July 31, 2024
Clinicaltrials.gov Registration #:
 NCT04016415
Important Instructions for Using This Protocol Template:
This template is provided to help investigators prepare a protocol that includes the necessary information needed by the 
IRB to determine whether a study meets all applicable criteria for approval.
1.
GENERAL INSTRUCTIONS:  

Prior to completing this protocol, ensure that you are using the most recent version by verifying the 
protocol template version date in the footer of this document with the current version provided in the 
CATS IRB Library.

Do not change the protocol template version date located in the footer of this document.

Some of the items may not be applicable to all types of research.  If an item is not applicable, please 
indicate as such or skip question(s) if indicated in any of the instructional text. 

GRAY INSTRUCTIONAL BOXES: 
o
Type your protocol responses below the gray instructional boxes of guidance language.  If the 
section or item is not applicable, indicate not applicable.
o
Penn State College of Medicine/Penn State Health researchers: Delete the instructional boxes 
from the final version of the protocol prior to upload to CATS IRB (http://irb.psu.edu).  
o
Penn State researchers at all other campuses: Do NOT delete the instructional boxes from the 
final version of the protocol.

Add the completed protocol template to your study in CATS IRB (http://irb.psu.edu) on the “Basic 
Information” page.  
2.
CATS IRB LIBRARY: 

Documents referenced in this protocol template (e.g. SOP’s, Worksheets, Checklists, and Templates) can be 
accessed by clicking the Library link in CATS IRB (http://irb.psu.edu).
3.
PROTOCOL REVISIONS: 

When making revisions to this protocol as requested by the IRB, please follow the instructions outlined in 
the Study Submission Guide available in the Help Center in CATS IRB (http://irb.psu.edu) for using track 
changes. 

Update the Version Date on page 1 each time revisions are made.
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If you need help…
University Park and other campuses:
Office for Research Protections Human Research 
Protection Program
The 330 Building, Suite 205
University Park, PA 16802-7014
Phone: 814-865-1775
Fax: 814-863-8699
Email: irb-orp@psu.edu
College of Medicine and Penn State Health:
Human Subjects Protection Office
90 Hope Drive, Mail Code A115, P.O. Box 855
Hershey, PA 17033
(Physical Office Location: Academic Support Building 
Room 1140)
Phone: 717-531-5687
Email: irb-hspo@psu.edu  
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Table of Contents
1.0
Objectives
2.0
Background
3.0
Inclusion and Exclusion Criteria
4.0
Recruitment Methods
5.0
Consent Process and Documentation
6.0
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
7.0
Study Design and Procedures
8.0
Subject Numbers and Statistical Plan
9.0
Data and Safety Monitoring Plan
10.0
Risks
11.0
Potential Benefits to Subjects and Others
12.0
Sharing Results with Subjects
13.0
Subject Payment and/or Travel Reimbursements
14.0
Economic Burden to Subjects
15.0
Resources Available
16.0
Other Approvals
17.0
Multi-Site Study
18.0
Adverse Event Reporting
19.0
Study Monitoring, Auditing and Inspecting
20.0
Future Undetermined Research: Data and Specimen Banking
21.0
References
22.0
Confidentiality, Privacy and Data Management
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1.0
Objectives
1.1
Study Objectives
The purpose of this study is to conduct a randomized controlled trial to determine the effects of a 6-
month live online Mindfulness-based stress reduction (MBSR) intervention compared to an active 
control Stress Management Education (SME) on glucose control in adults with uncontrolled diabetes. 
We will randomize 290 adults with uncontrolled diabetes to a 6-month MBSR intervention or SME 
control. Both MBSR and SME will be delivered online by experienced instructors in a live interactive 
virtual classroom using videoconferencing. Outcomes will be assessed at baseline, a follow-up phone call 
after Class #4, and study visits at 2-months and 6-months. The specific aims of the study are: 
Specific Aim 1: To conduct a randomized controlled trial to determine the effects of a 6-month live 
online MBSR intervention compared to an active control SME on glucose levels in 290 adults with 
uncontrolled diabetes. The primary outcome will be hemoglobin A1c (HbA1c), a measure of the average 
glucose level over the past 3 months. We hypothesize that between the two groups, there will be a 
clinically significant 0.5% absolute difference in the mean change in HbA1c from baseline to 6-months. 
We will also look at the 2-month HbA1c, however it may be too brief a time period to fully capture the 
impact of MBSR. An absolute reduction in HbA1c of 0.5% would be expected to reduce the risk of any 
diabetes-related complication by at least 10% (Stratton et al., 2000). We will assess fasting glucose as a 
secondary outcome as it is linked with adverse health outcomes (Barr et al., 2007; Schmidt et al., 2005), 
and can be lowered with MBSR based on our pilot study (Raja-Khan et al., 2017). 
Specific Aim 2: To determine the effects of live online MBSR compared to SME control on 
psychosocial, behavioral and physiological mechanisms potentially mediating the effects of MBSR 
and/or SME on glucose levels in adults with uncontrolled diabetes.  Secondary outcomes include: 
diabetes-related distress, subjective stress, craving, the impact of COVID-19 on subjects’ lives, and 
subject expectancy. Adverse Childhood Experiences (ACEs) will be assessed at baseline. It is 
hypothesized that these measures may mediate the effects of MBSR and/or SME on glucose.  
1.2
Primary Study Endpoints
The primary outcome will be hemoglobin A1c (HbA1c) at the 6-month visit, a measure of average 
glucose control over the past 3 months.
1.3
Secondary Study Endpoints
Secondary outcomes include: diabetes-related distress, subjective stress, craving, the impact of COVID-
19 on subjects’ lives, subject expectancy, and other physiologic, behavioral and psychosocial measures.
2.0
Background 
2.1
Scientific Background and Gaps
Diabetes is a serious public health problem that affects nearly 30 million people in the U.S. (Center for 
Disease Control and Prevention, 2017; American Diabetes Association, 2013). Stress is present in 45% of 
patients with diabetes (Nicolucci et al., 2013), and related to significantly worse glucose control, 
medication adherence, unhealthy lifestyle behaviors, and reduced quality of life (Hackett & Steptoe, 
2017; Crump et al., 2016; Curry, 2016; Downs & Faulkner, 2015; Kelly & Ismail, 2015; Steptoe, 2016; 
Siddiqui et al., 2015; Fisher et al., 2010; Aikens, 2012; Hessler et al., 2014). Additionally, there is a high 
prevalence of stress-related conditions in diabetes, including 8.7-17.6% prevalence of depression (Ali et 
al., 2006; Vancampfort et al., 2015), 20% increased risk of anxiety disorder, and 48% increased risk of 
anxiety symptoms (Smith et al., 2013). This is significant because managing a chronic disease like 
diabetes is stressful, and perceived stress, subclinical psychological distress, and diabetes-related 
distress, can all adversely affect outcomes in diabetes (Hackett & Steptoe, 2017). Several national and 
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international guidelines recognize the adverse effects of stress on diabetes (Barnard et al., 2012). 
However, implementation of effective stress reduction strategies for diabetes remains a widespread 
challenge as no stress reduction intervention to date has been shown to definitively and consistently 
lower blood glucose (Barnard et al., 2012).
The current standards of care for diabetes include pharmacologic treatment and lifestyle management 
(American Diabetes Association, 2019a). Lifestyle management includes Diabetes Self-management 
Education and Support (DSMES), medical nutrition therapy (MNT), physical activity, smoking cessation 
counseling, and psychosocial care. However, mindfulness-based interventions are not specifically 
included in the standards of care for diabetes. 
Figure 1 demonstrates a comprehensive model of the biological pathways by which stress potentially 
contributes to poor glucose control and diabetes. This project will assess the effects of MBSR on a 
meaningful subset of these constructs in adults with uncontrolled diabetes. The study intervention, 
MBSR, is available to the patient without taking part in the study.
Figure 1. Overview of the biological pathways by which stress potentially impacts diabetes.
If the proposed aims are achieved and MBSR improves glucose control in patients with diabetes, it could 
transform diabetes treatment by supporting the inclusion of MBSR in the standards of care for diabetes 
so that patients are empowered with skills for strengthening their internal resources, reducing stress 
reactivity, and building resilience in the face of a chronic disease like diabetes, which are all essential for 
implementing healthy behaviors and improving self-management of diabetes. Finally, if longer-term 
MBSR is found to be beneficial in patients with diabetes, it could have a broader impact and also be 
STRESS 

Subjective stress 

Diabetes-related distress 

Adverse Childhood Experiences (ACEs)
Behavioral 

Diet 

Physical activity 

Medication adherence 

Self-monitoring of blood 
glucose 
Psychosocial

Depressive symptoms, 
Anxiety, Affect & Emotion 

Cognition/Decision-
making/Self-Regulation

Stress Reactivity & 
Resilience

Interpersonal & Social 
Processes

Spirituality 

Disability 
DIABETES

INCREASED BLOOD GLUCOSE 

Increased blood pressure, weight and lipids 
Physiological*

HPA axis- cortisol 

Sympathetic nervous system- salivary 
α-amylase

Chronic inflammation- hsCRP and 
TNF-α
 *All contribute to Insulin Resistance and 
Obesity 
MBSR

Mindfulness 

Intervention fidelity and quality 

Instructor characteristics 
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beneficial in patients with other chronic diseases that have also been linked with increased stress and 
adverse health outcomes.
2.2
Previous Data
We completed a pilot RCT of MBSR compared to health education in 86 overweight or obese women 
with high subjective stress (mean Perceived Stress Scale-10 score of 22.2), including women with type 2 
diabetes and prediabetes. As demonstrated in Figure 2, we found a significant reduction in fasting 
glucose in the MBSR group that was not seen in the health education control group [MBSR group: at 8 
weeks -8.9 mg/dl, P = 0.02; at 16 weeks -9.3 mg/dl, P = 0.02] (Raja-Khan et al., 2017). The reason for the 
reduced fasting glucose in the MBSR group remains unclear. There were no changes in weight, salivary 
cortisol, or insulin resistance to explain the reduction in glucose. One possible explanation is that the 
increased mindfulness and decreased perceived stress could have made it easier for the MBSR group to 
adhere to the diet and exercise guidelines prescribed.
A recent systematic review of mindfulness-based interventions in diabetes showed that four of seven
studies successfully lowered HbA1c levels (Noordali et al., 2017). Previous randomized studies of 
mindfulness-based interventions in diabetes are limited by small sample size, short duration of 
intervention, and lack of active control, long-term follow-up, and rigorous assessment of intervention 
fidelity and quality and instructor characteristics as shown in Table 1 (Gregg et al., 2007; Kopf et al., 
2014; Miller et al., 2014; Van Son et al., 2014). The standard MBSR program has a duration of only 8 
weeks, and is too brief an intervention to determine a significant impact on hemoglobin A1c, which 
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reflects average glucose control over the past 3 months. A longer MBSR intervention and follow-up is 
needed to determine the full impact of MBSR in diabetes.
Table 1. Randomized trials of mindfulness-based group interventions in adults with diabetes.
2.3
Study Rationale
The proposed project uses mindfulness-based stress reduction (MBSR), a well-researched mindfulness-
based intervention, to address stress as a critical barrier to glucose control in patients with diabetes. 
Stress is increasingly being recognized as an important factor contributing to poor glucose control and 
complications in individuals with diabetes (Hackett & Steptoe, 2017; Crump et al., 2016; Curry, 2016; 
Downs & Faulkner, 2015; Kelly & Ismail, 2015; Steptoe, 2016; Siddiqui et al., 2015; Fisher et al., 2010; 
Aikens, 2012; Hessler et al., 2014). Figure 1 demonstrates a comprehensive model of the biological 
pathways by which stress potentially contributes to poor glucose control in diabetes. This project will 
assess the effects of MBSR on a meaningful subset of these constructs in adults with uncontrolled type 1 
or type 2 diabetes. Although the etiological mechanisms underlying type 1 and type 2 diabetes are 
different, and individuals with type 2 diabetes have greater pancreatic beta cell reserve, the clinical 
manifestations and stressors of type 1 and type 2 diabetes are similar. Therefore, both adults with type 
1 diabetes and adults with type 2 diabetes are likely to benefit from MBSR.
Mindfulness is among the top 50 priority topics for comparative effectiveness research recommended 
by the Institute of Medicine (2009). A comparative effectiveness review concluded that “Meditation 
programs, in particular, mindfulness programs, reduce multiple negative dimensions of psychological 
stress." (Goyal et al., 2014). Mindfulness-based stress reduction has been shown to reduce stress in 
various patient populations (Raja-Khan et al., 2017; Ludwig & Kabat-Zinn, 2008; Merkes, 2010; Nyklicek 
& Kuijpers, 2008; Burnett-Zeigler et al., 2016). In support of the biological pathways outlined in Figure 1, 
several systematic reviews and meta-analyses suggest that mindfulness based interventions such as 
MBSR have psychological, behavioral and physiological benefits in patients with chronic diseases (Levine 
et al., 2017; Rogers et al., 2017; Ruffault et al., 2017; Carriere et al., 2018; O’Reilly et al., 2014). 
Dispositional mindfulness, an inherent but modifiable trait of the capacity to attend and to be aware of 
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what is occurring in the present moment, has been inversely linked with obesity, a highly prevalent 
precursor to type 2 diabetes (Loucks et al., 2016). Mindfulness may be a novel determinant for glucose 
control in individuals with diabetes as it increases self-regulation and the ability to notice but not act on 
cravings (Epstein, 1999; Sedlmeier et al., 2012; Brewer et al., 2011; Loucks et al., 2015). Thus, one way 
MBSR could be helpful in the self-management of diabetes is by limiting the overconsumption of 
palatable high carbohydrate foods that increase blood glucose. Furthermore, as MBSR decreases stress 
and positively affects other key psychological factors often overlooked in standard approaches to 
diabetes, MBSR could significantly impact the clinical picture of diabetes by empowering patients with 
diabetes to adopt healthier behaviors (diet, exercise, self-monitoring of blood glucose, medication 
adherence) that improve their glucose control and reduce their risk of diabetes complications. MBSR 
could have beneficial physiologic effects on the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic 
nervous system, and chronic inflammation, leading to reduced insulin resistance and improved blood 
glucose (Davidson et al., 2003; Carlson & Garland, 2005; Carlson et al., 2007; Winbush et al., 2007). 
MBSR could also exert beneficial effects by altering gene expression (Black & Slavich, 2016; Creswell et 
al., 2012; Dusek et al., 2008), as well as brain structure and function (Gotink et al., 2016; Mascaro et al., 
2015; Muehsam et al., 2017; Santarnecchi et al., 2014). Several of these potential underlying 
mechanisms may act synergistically to mediate the impact of MBSR in diabetes.
3.0
Inclusion and Exclusion Criteria
3.1
Inclusion Criteria
1. Men and Women
2. Age 18 years or older
3. Diagnosed with diabetes for at least one year
4. Hemoglobin A1c ≥ 7.5% within 12 weeks and 2 days (86 days) before the start of the study 
intervention (Orientation session)  
5. High Subjective stress defined as Perceived Stress Scale-10 score ≥ 12
6. Available for the intervention sessions with reasonable certainty
7. Have a device equipped with internet connection, camera and microphone and willingness to interact 
with study staff and class instructors virtually/remotely via this platform
8. Must have a Primary Care Provider (PCP)
9. Must have an accessible/active personal e-mail address or be willing to obtain one for study 
correspondence 
3.2
Exclusion Criteria
1. Current suicidality
2. History of, or meets MINI structured interview criteria for bipolar disorder, psychosis, or other 
significant psychopathology; those with depression or anxiety will be allowed to participate since they 
are under the care of a PCP.
3. Inpatient admission for psychiatric disorder within the past two years, or ER visit for psychiatric 
disorder within the past 10 weeks 
4. Meets MINI structured interview criteria for Alcohol Use Disorder or Substance Use Disorder (Past 12 
months)
5. Inability to read, write or speak English
6. Current enrollment in a stress reduction program, or in any other investigative study
7. Previous participation in a mindfulness-based stress reduction (MBSR) course 
8. Pregnant women
9. Have a household member who is currently, or was previously, assigned to study treatment 
The following MINI criteria are considered exclusionary under the umbrella of significant 
psychopathology: 

Manic Episode – Current
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
Hypomanic Episode – Current

Hypomanic Symptoms – Current

Bipolar I Disorder – Current

Bipolar I Disorder – Past

Single Manic Episode – Current

Bipolar I Disorder with Psychotic Features – Current

Bipolar I Disorder with Psychotic Features – Past

Bipolar II Disorder – Current

Bipolar II Disorder – Past

Other Specified Bipolar and Related Disorder – Current

Other Specified Bipolar and Related Disorder – Past

Alcohol Use Disorder – Past 12 Months

Substance Use Disorder (Non-Alcohol) – Past 12 Months 

Any Psychotic Disorder – Current

Any Psychotic Disorder – Lifetime

Mood Disorder with Psychotic Features – Current

Mood Disorder with Psychotic Features – Lifetime

Psychotic Disorder – Current

Psychotic Disorder – Lifetime

Major Depressive Disorder with Psychotic Features – Current

Major Depressive Disorder with Psychotic Features – Past

Bipolar I Disorder with Psychotic Features – Current

Bipolar I Disorder with Psychotic Features – Past

Antisocial Personality Disorder – Lifetime
Women who are pregnant at the time of screening are not eligible to continue in the study. Women 
who become pregnant any time after screening, will not be allowed to continue in the study.
3.3
Early Withdrawal of Subjects
3.3.1
Criteria for removal from study
Subjects will be removed from the study for safety reasons as described below based on the 
PHQ-9, pregnancy clinical criteria (history with pregnancy testing as indicated), and PI AE review, 
or if they withdraw consent. 
3.3.2
Follow-up for withdrawn subjects
Subjects will be advised that they may withdraw from the study at any time by writing or calling 
to inform the PI Dr. Nazia Raja-Khan that they are withdrawing from the research study. At the 
time of withdrawal, the reason for the withdrawal will be recorded. 
4.0
Recruitment Methods
4.1
Identification of subjects
Subjects will be recruited from a variety of sources within and outside our health care systems. One 
source will be Dr. Raja-Khan’s clinical subspecialty practice of Endocrinology, as well as our larger 
departmental clinical practices of Internal Medicine and Family Medicine at Penn State Health Practice 
Sites. An Enterprise Information Management (EIM) Design Specification Form will be submitted up to 
once per month to request data on subjects that meet study criteria.  Another source will be subjects 
who participated in our prior studies and agreed to be contacted again about future studies. Patients 
will be recruited at the annual Diabetes Fair held at the University Conference Center in November, 
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Diabetes Support Group meetings held on campus, and at other health fairs and support groups, and 
community events within and outside our health care system. The study has been posted on 
StudyFinder and registered at ClinicalTrials.gov. Recruitment will also be done via an official De-stress 
Study website, ResearchMatch, HealthGrades, social media (Facebook, Reddit, Instagram, etc.), and 
through means such as posted flyers and generic letters and emails.
4.2
Recruitment process
4.2.1
How potential subjects will be recruited.
Potential subjects will be recruited from Endocrinology, Internal Medicine and Family medicine 
clinical practices at Penn State Health Hershey Medical Center, as well as from the larger Penn 
State Health system and nationally. The EIM search will not be limited to those who have been 
seen by the departmental practice locations. We will potentially recruit PSH patients who meet 
the eligibility criteria but have no prior relationship with Dr. Raja-Khan or the Department of 
Medicine. For such patients, in accordance with IRB policy, we will work with the other 
Departments so that the initial contact, regardless of method, comes from a person who can be 
expected to be reasonably familiar to the potential research participant, such as a physician or 
health care provider directly engaged in the patient’s clinical care or an acceptable 
representative or a physician or health care provider from the clinical unit in which the patient 
has been seen, or a referring physician. We will promote the study by maintaining ongoing 
contact with the clinical practices, faculty members and residents in our departments, 
reminding them of the inclusion criteria, importance of the study, etc. We will present the study 
at staff meetings, and lunch and learns. The study has been posted on StudyFinder and 
registered at ClinicalTrials.gov. 
Participants will be recruited via ResearchMatch.  ResearchMatch is an online resource funded 
in part by the NIH CTSA.  It is operated through Vanderbilt and connects researchers with 
patients.  A recruitment message will be uploaded and sent to participants who match the 
inclusion criteria.  Participants will be allowed to accept or reject the invitation. For those that 
accept, an automated message (via Redcap Survey) will request basic pre-screening information 
as well as their phone numbers and emails from them. A coordinator will contact those who are 
preliminarily eligible to participate in the study. 
Participants will also be recruited via HealthGrades. Healthgrades CRM (Customer Relationship 
Management) is a multi-function platform used to identify and communicate with current Penn 
State Health patients as well as prospective patients from our local coverage communities. 
Electronic Medical Record data is securely provided and Healthgrades adds publicly available 
consumer health data to provide us with a databank which we can utilize to target prospective 
patients in need of specific healthcare services. Predictive modeling and known diagnoses data 
combine to enable identification of and messaging to the populations most related to the 
service line seeking additional patients. Email, direct mail, and search engine marketing are 
employed to engage patients and invite them into the Penn State Health system.
A Facebook page template has been made to be added to the official Penn State College of 
Medicine Facebook page and for multiple Diabetes Facebook pages, such as: American Diabetes 
Association, Diabetes Action Research and Education Foundation, Diabetes Research Institute 
Foundation, and American Diabetes Association-DiabetesPro. The Facebook page template will 
also be used for Facebook groups, for example: Type 1 Diabetes Support Group (the One And 
Only Original), Women’s Support Group for Type 1 Diabetes, Diabetes Strong Community, Type 
2 Diabetes Friends, Diabetic Support Group, Physician Moms Group (PMG), and others. The 
study team may find additional groups and pages to post in beyond these examples. Study team 
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members will first message group moderators and ask them to post on behalf of the study team, 
ensuring it is clear that it is IRB-approved content and cannot be altered. 
Posts will be made about this study in specified “subreddit” communities, with approval from 
the subreddits’ moderators. Examples of specific subreddits the study team will request to post 
in are: r/diabetes, r/diabetes_t2, r/diabetes_t1, r/Type1Diabetes, and r/type2diabetes. The 
study team may find additional subreddits to post in beyond these examples. An official De-
stress Study website will be used to serve as a landing page for digital recruitment efforts.  
Research flyers will be posted throughout HMC campus, Penn State Health practice sites and will 
be distributed at Diabetes Support Group meetings and Diabetes Education Classes. Flyers will 
also be posted at pharmacies, community partner sites (e.g. PSH Community Health Needs 
Assessment (CHNA) forum registrants, etc.), hospitals (e.g. York Hospital, Lancaster General 
Hospital, etc.), clinics (e.g. WellSpan, Allegheny Health Network, UPMC, private practices, etc.), 
senior homes, and other healthcare facilities outside of Penn State Health after receiving 
permission to post flyers.  We will also recruit subjects at the Diabetes Fair and The Diabetes 
Symposium held every November. We will also post the study flyer on the Lion’s Eye TV screens. 
We will promote the study on Penn State University newswires and in newsletters such as the 
PaTH to Health: Diabetes Newsletter. 
Once data on subjects that meet study criteria is extracted from the EIM, emails and/or letters 
will be sent out to potential subjects using a generic template. Providers (physicians, nurse 
practitioners, physician assistants, diabetes educators, etc.) will also be reached via a general 
email template and/or Doximity to inform them of our study.
Potential subjects who may be interested will be put in contact with the research coordinator. 
We will track all contact from subjects interested in the study. We will develop a pre-screening 
list that documents date and point of contact, eligibility based on telephone or in-person pre-
screening and follow-up if the subject meets prescreening and is interested in participation. 
Available medical records will be reviewed during the pre-screening assessment to verify 
recruitment of subjects that meet the medical record-applicable inclusion/exclusion criteria, 
when possible. 
The consent process will take place in-person or via videoconferencing at the screening visit, 
which will be scheduled during the pre-screening assessment (conducted via a phone call or in-
person) if the subject is interested in and eligible for the study at the time of the pre-screening 
assessment. The consent form document will be emailed or mailed to potential subjects prior to 
the screening visit to provide ample time for the subjects to review it prior to the screening visit.  
Consent will be obtained by the research coordinator, not the subject's physician. Potential 
subjects will be reassured that choosing not to participate will not jeopardize their medical care.
4.2.2
Where potential subjects will be recruited.
Potential subjects will be recruited from Penn State Health Practice Sites including 
Endocrinology, Internal Medicine, and Family Medicine clinical practices. Subjects will be 
recruited at the annual Diabetes Fair held at the University Conference Center and at the 
Diabetes Support Group meetings held on campus and at off site Penn State Health sites.  Flyers 
will be posted at pharmacies, community partner sites (e.g. PSH Community Health Needs 
Assessment (CHNA) forum registrants, etc.), hospitals (e.g. York Hospital, Lancaster General 
Hospital, etc.), clinics (e.g. WellSpan, Allegheny Health Network, UPMC, private practices, etc.), 
senior homes, and other healthcare facilities outside of Penn State Health. The study will also be 
posted on StudyFinder and registered at ClinicalTrials.gov. Potential subjects will also be 
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recruited via an official De-stress Study website, ResearchMatch, HealthGrades, and social 
media (Facebook, Reddit, Instagram, etc.).
4.2.3
When potential subjects will be recruited.
We will recruit no more than 520 subjects in order to reach the randomization target of 290 
subjects.  We expect to reach this target by randomizing 36 subjects by month 30, 72 subjects by 
month 36, 120 subjects by month 42, 174 subjects by month 48, 230 subjects by month 54, and 
at least 290 subjects (but no more than 320 subjects) by month 60. 
4.2.4
Describe the eligibility screening process and indicate whether the screening process will 
occur before or after obtaining informed consent. Screening begins when the investigator 
obtains information about or from a prospective participant in order to determine their 
eligibility.  In some studies, these procedures may not take place unless HIPAA Authorization 
is obtained OR a waiver of HIPAA Authorization when applicable for the screening procedures 
is approved by the IRB.  [For FDA regulated studies, consent for any screening activities would 
need to be obtained prior to screening unless specifically waived by the IRB.]
We will use a telephone or in-person pre-screening form when potential subjects contact in 
response to the various ways of recruitment. During pre-screening, available medical records 
will be reviewed to ensure we only recruit those subjects that meet the inclusion/exclusion 
criteria. During prescreening potential subjects will also be informed of the dates and times of 
the classes that they could be assigned to and the requirement of home practice. For the 
purposes of the study, subjects will be told that they are expected to do at least 25 to 30 
minutes of home practice per day for 6 out of 7 days per week. Then they will be asked if they 
are able to participate in the program with reasonable certainty. If a subject thinks they will miss 
the Orientation, and won’t be able to complete a makeup orientation session prior to Class #2, 
or if they think they will miss more than 2 classes during the first 8 weeks (including Class #1 to 8 
and the Retreat), they will be encouraged to wait for another wave/cohort when they are able 
to make the time commitment. This prescreening process will occur before obtaining informed 
consent as it will help study coordinators to assess basic eligibility to warrant a screening visit. 
Informed consent will be obtained in-person or via videoconferencing at the screening visit, 
which will be scheduled during the pre-screening assessment. Eligibility will be further assessed 
at the screening visit and baseline visit. Additionally, a randomization phone call will be made 
within 1 week prior to the Orientation session, and if a subject is no longer available or 
interested in participating, they will be treated as a screen failure and will not be randomized.
5.0
Consent Process and Documentation 
5.1
Consent Process:
Check all applicable boxes below:
 Informed consent will be sought and documented with a written consent form [Complete Sections 
5.2 and 5.6] 
 Implied or verbal consent will be obtained – subjects will not sign a consent form (waiver of 
written documentation of consent) [Complete Sections 5.2, 5.3 and 5.6] 
  Informed consent will be sought but some of the elements of informed consent will be omitted or 
altered (e.g., deception). [Complete section 5.2, 5.4 and 5.6] 
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 Informed consent will not be obtained – request to completely waive the informed consent 
requirement. [Complete Section 5.5]
The following checkbox is for all locations EXCEPT Penn State Health and College of Medicine: 
 
 Exempt Research at all Locations Except Penn State Health and the College of Medicine: If you 
believe that the research activities outlined meet one or more of the criteria outlined in “HRP-312- 
Worksheet- Exemption Determination.” Please verify by checking this box that if conducting an 
exempt research study, the consent process will disclose the following (all of which are included in 
“HRP-590- Consent Guidance for Exempt Research”):
Penn State affiliation; name and contact information for the researcher and advisor (if the 
researcher is a student); the activities involve research; the procedures to be performed; 
participation is voluntary; that there are adequate provisions to maintain the privacy interests of 
subjects and the confidentiality of the data; and subjects may choose not to answer specific 
questions.  
If the research includes the use of student educational records include the following language in 
this section (otherwise delete): The parent or eligible student will provide a signed and dated 
written consent that discloses: the records that may be disclosed; the purpose of the disclosure; the 
party or class of parties to whom the disclosure may be made; if a parent or adult student requests, 
the school will provide him or her with a copy of the records disclosed; if the parent of a student 
who is not an adult so requests, the school will provide the student with a copy of the records 
disclosed.
Note: If this box has been checked, skip the remainder of section 5 and proceed to section 6 of this 
protocol. If the investigator’s assessment is inaccurate, an IRB Analyst will request revision to the 
protocol and that an informed consent form be submitted for review and approval. Except for 
exemptions where Limited IRB Review (see “HRP-312- Worksheet- Exemption Determination”) is 
required or where otherwise requested by the IRB, informed consent forms for research activities 
determined to be exempt without Limited IRB Review are generally not required to be submitted 
for review and approval by the University Park IRB. 
5.2
Obtaining Informed Consent 
5.2.1
Timing and Location of Consent 
A subject who qualifies for further screening at the time of the pre-screening assessment will be 
scheduled for the screening visit at the CRC at Hershey Medical Center within 10 weeks and 2 
days (72 days) before the start of the study intervention (within 72 days before the Orientation 
session for each cohort/wave). If the screening visit cannot be conducted in the CRC due to 
COVID-19, or at the preference of the subject, a Penn State Health (PSH) Teams meeting will be 
set up and patients will be consented remotely with a witness to the consent on the  PSH Teams 
session. A blank PDF copy of the most currently approved Informed Consent will be emailed to 
the subject prior to the Screening  PSH Teams Meeting. During the scheduled Screening  PSH 
Teams Meeting, the study team will send the participant an email with a link to the eConsent 
survey. This email will also contain a confirmation of the scheduled date and time to consent the 
potential participant along with another blank PDF copy of the consent for the potential 
participant to review. At this time the study team member will direct the potential participant to 
open the previously sent eConsent survey link, which can be opened on any device that has 
access to the internet. The consenter will give a brief overview of how to navigate through the 
eConsent survey (i.e. how to enlarge the font, how to move through each page, and how to save 
and return). The eConsent process will allow for potential participants to proceed forward or 
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backward or pause for review later. The Informed Consent will be reviewed with the subject in 
its entirety, and the subject will be encouraged to ask any questions they may have regarding 
the study. The study team will instruct the potential participant to answer and complete the 
questions they will be asked including, do you wish to participate in this study, first name, last 
name, email address and signature. All of the questions the potential participant will be asked 
on the eConsent are required and need to be completed prior to the potential participant being 
able to continue on the next page. The consenter will instruct the participant to add their 
signature by using their mouse, if on a computer, or finger if using a tablet or cell phone, to sign 
their name. The optional sections of the study will also be explained by the consenter, and the 
potential participant will be instructed to check either Yes or No beside each optional 
component. After the last optional part, the potential participant must sign their name again. 
The final step for the participant is to review, certify, and submit the consent form. The 
participant will be taken to the final page of the eConsent survey, which will allow them to 
download a signed copy of the consent and/or send themselves an email with the signed 
consent with their signatures only. To complete the eConsent process, the consenter will sign 
the consent survey by adding their signature to the relevant sections, which automatically 
generates a merged signed eConsent file. The consenter will download the completed signed 
consent and send this completed eConsent form to the study participant via email.
If the potential participant requires a physical copy of the consent to obtain their consent for 
any reason, it will be mailed several days prior to the Consent PSH Teams Visit. A PSH Teams 
meeting will be set up and patients will be consented remotely with a witness to the consent on 
the  PSH Teams session. A blank PDF copy of the most currently approved Informed Consent will 
be emailed to the subject prior to the Consent  PSH Teams Meeting. During the Consent  PSH 
Teams Meeting, the consenter will explain in-detail all aspects of the study procedures, review 
the entirety of the consent, and allow for multiple opportunities to ask questions. The subject 
will sign the consent, witnessed by the Research Coordinator when the participant is instructed 
to hold up the consent to the camera for verification after each signature. The subject can 
return the signed consent to the study team via regular mail, fax, or secure email. No study 
procedures will be performed, and no Screening  PSH Teams Visit will be done, until the study 
staff has the subject’s signed consent in hand. 
At the Screening Visit in-person at the CRC, the consent process will take place in a private room 
setting and prior to any study procedures.  The subject will initially be counseled about the 
purpose of the study, the procedures, the risks, and the time commitment.  Voluntariness will 
be stressed and ample time will be given for discussion and questions.  Informed consent is 
obtained in person, or via PSH Teams, by study personnel, and the subject also has the 
opportunity to interact with one of the study investigators who reviews eligibility criteria.  All 
subjects give written informed consent to participate in the study during this screening visit and 
will be given a copy of the signed document, or have the option to be emailed or mailed a copy 
of the signed document if the consent takes place via PSH Teams.
5.2.2
Coercion or Undue Influence during Consent 
The study team will stress voluntariness of participation in the research study. Consent will be 
obtained by the research coordinator, not the subject's physician. Potential subjects will be 
reassured that choosing not to participate will not jeopardize their medical care.  
5.3
Waiver of Written Documentation of Consent 
Not applicable
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5.4
Informed consent will be sought but some of the elements of informed consent will be omitted or 
altered (e.g., deception).
Not applicable
5.5
Informed consent will not be obtained – request to completely waive the informed consent 
requirement
Not applicable
5.6
Consent – Other Considerations 
5.6.1
Non-English-Speaking Subjects
Not applicable
5.6.2
Cognitively Impaired Adults
5.6.2.1 Capability of Providing Consent
Not applicable
5.6.2.2
Adults Unable to Consent
Not applicable
5.6.2.3 Assent of Adults Unable to Consent
Not applicable
5.6.3
Subjects who are not yet adults (infants, children, teenagers) 
5.6.3.1 Parental Permission
Not applicable
5.6.3.2 Assent of subjects who are not yet adults
Not applicable
6.0
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
6.1
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
Check all that apply:
 
Not applicable, no identifiable protected health information (PHI) is accessed, used or 
disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable]
Authorization will be obtained and documented as part of the consent process. [If this is the 
only box checked, mark sections 6.2 and 6.3 as not applicable]
Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical 
records will be accessed to determine eligibility before consent/authorization has been 
obtained). [Complete all parts of sections 6.2 and 6.3]
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Full waiver is requested for entire research study (e.g., medical record review studies). 
[Complete all parts of sections 6.2 and 6.3]
Alteration is requested to waive requirement for written documentation of authorization 
(verbal authorization will be obtained). [Complete all parts of sections 6.2 and 6.3]
6.2
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
6.2.1
Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of the 
individual
6.2.1.1
Plan to protect PHI from improper use or disclosure
Information is included in the “Confidentiality, Privacy and Data 
Management” section of this protocol.
6.2.1.2
Plan to destroy identifiers or a justification for retaining identifiers 
Identifiers will be stored securely within REDCap upon completion of the pre-
screening phone call or in-person assessment. These identifiers will be 
retained as part of the study’s pre-screening database securely within 
REDCap to keep track of duplicate screening events. If the subject does not 
consent to the storage/retaining of their information during the pre-
screening phone call, the interview will be stopped and any collected data, 
including PHI collected via EIM search, will be deleted from REDCap. Contact 
information and any applicable data for subjects who consented to the 
storage of their identifiable contact information for future possible research 
studies will be retained indefinitely.  
6.2.2
Explanation for why the research could not practicably be conducted without access to and 
use of PHI
Pre-screening efforts could not practicably be conducted without viewing the medical record 
and hence use/access to PHI.
6.2.3
Explanation for why the research could not practicably be conducted without the waiver or 
alteration of authorization
Partial waiver for recruitment purposes is necessary to review available medical records during 
the pre-screening assessment to ensure we only recruit those subjects that meet the 
inclusion/exclusion criteria.
6.3
Waiver or alteration of authorization statements of agreement
Protected health information obtained as part of this research will not be reused or disclosed to any other 
person or entity, except as required by law, for authorized oversight of the research study, or for other 
permitted uses and disclosures according to federal regulations. 
The research team will collect only information essential to the study and in accord with the ‘Minimum 
Necessary’ standard (information reasonably necessary to accomplish the objectives of the research) per 
federal regulations. 
Access to the information will be limited, to the greatest extent possible, within the research team. All 
disclosures or releases of identifiable information granted under this waiver will be accounted for and 
documented.
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7.0
Study Design and Procedures
7.1
Study Design
This is a randomized, parallel group two-arm trial that will determine the effects of a 6-month live online 
MBSR intervention compared to an active control Stress Management Education (SME) on glucose 
control in 290 adults with uncontrolled diabetes. The proposed 6-month MBSR intervention will consist 
of the 8-week University of Massachusetts MBSR curriculum (Santorelli et al., 2017), adapted for live 
online delivery due to the COVID-19 pandemic, followed by live online mindfulness booster sessions 
every month for 4 months. Subjects will be randomized to one of two groups: (1) MBSR, or (2) SME 
control. Both MBSR and SME will be delivered online by experienced instructors in a live interactive 
virtual classroom using videoconferencing. Outcomes will be assessed at baseline, a follow-up phone call 
after Class #4, and study visits at 2-months and 6-months. If study visits cannot be conducted in person 
due to COVID-19, or the preference of the subject, study visits will be conducted remotely using 
videoconferencing and all data that can be collected remotely will be obtained, including the home 
hemoglobin A1c using the Home A1CNow Self Check kit, urine pregnancy test when applicable, diabetes 
device data, and surveys. Figure 3 shows the flow chart of the proposed study.
Figure 3. Flow Chart of Proposed Study
Mindfulness-based stress reduction (MBSR)
 X 6 months (N =145)
(Live online 8-week MBSR program followed by 
monthly booster sessions for 4 months)
Stress Management Education (SME) Active Control
X 6 months (N = 145)
(Live online 8-week SME program followed by monthly 
booster sessions for 4 months) 
Men and women age 18 years or older with 
uncontrolled diabetes (N ~ 480)
Eligibility Screening and Baseline Evaluations of 
Physiologic, Behavioral and Psychosocial 
measures
      RANDOMIZATION (N = 290)
 Follow-up Phone Call after Class #4 (middle of 8-week 
MBSR or SME intervention): 
Hypoglycemia Survey and Stress Experience Survey
2-month Study Visit (after 8-week MBSR or SME intervention)
6-month Study Visit (after Booster session #4/end of study)
Primary Outcome: Hemoglobin A1c
Key Secondary Outcomes: Diabetes-related distress, subjective stress, craving, the impact of COVID-
19 on subjects’ lives, subject expectancy, and other physiologic, behavioral and psychosocial measures
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7.2
Study Procedures
7.2.1
PRE-SCREENING procedures
We will use a pre-screening script when engaging with potential subjects via phone or in-person 
for preliminary assessment of study eligibility for the first time.  During pre-screening, available 
medical records will be reviewed to verify inclusion/exclusion criteria are met (in addition to 
self-report), whenever possible. Potential subjects will be informed of the dates and times of the 
classes for the upcoming cohort/wave, and of the requirement of home practice. For the 
purposes of the study, subjects will be told that they are expected to do at least 25 to 30 
minutes of home practice per day for 6 out of 7 days per week, and respond to an email survey 
once a day about their stress level, food cravings, and home practice (See Pre-Screening Phone 
call script). The subject will be counseled about the purpose of the study, the procedures, the 
risks, and the time commitment. The research coordinator will verify that the subject is available 
for the intervention sessions with reasonable certainty, and that they have a device (e.g. tablet, 
computer, laptop or smartphone) with internet connection, camera and microphone for 
participation in the live interactive videoconferencing (Zoom) sessions. If a subject thinks they 
will miss the Orientation, or if they think they will miss more than 2 classes during the first 8 
weeks (including Class #1 to 8 and the Retreat), they will be encouraged to wait for another 
wave/cohort when they are able to make the time commitment. This prescreening process will 
occur before obtaining informed consent as it will help study coordinators to assess basic 
eligibility to warrant the scheduling of a screening visit where informed consent will be obtained 
in-person or via videoconferencing. A copy of the consent form and the Class Schedule and 
Homework (class dates/times and required number of minutes of Homework will be the same 
for both groups) will be mailed/emailed to the subject so they can review it at home prior to the 
screening visit (See Class Schedule and Homework).  
7.2.2
Visit #0 (SCREENING VISIT and procedures)
After eligibility and interest has been assessed during prescreening  (via phone or in-person), a 
screening visit is scheduled at the Clinical Research Center (CRC) at Hershey Medical Center 
within 10 weeks and 2 days (72 days) before the start of the study intervention (within 72 days 
before the Orientation session). If the screening visit cannot be completed in the CRC due to 
COVID-19, or the preference of the subject, the screening visit will be completed remotely using 
videoconferencing (PSH Teams), and all data that can be collected remotely will be obtained. 
The screening visit will last approximately 2 hours.  Subjects will be asked to bring their diabetes 
devices (glucometers, continuous glucose monitor (CGM), insulin pump and other smart insulin 
delivery devices) to their remote or in-person screening visit so that the dates and times on 
these devices can be verified. If the subject does not have a glucometer, a letter will be sent to 
their primary care provider, PCP, asking them to prescribe a glucometer for the patient, and to refer 
the patient to a diabetes educator for glucometer teaching if the patient has never used a 
glucometer before. This is being done because it is the standard of care for patients with 
uncontrolled diabetes, and it is important to collect historical blood glucose levels on subjects for 
data analysis, before and after the subject attends stress management classes. Subjects will be able 
to obtain a glucometer with their physician’s prescription, and get the necessary education on its 
use. Subjects will NOT be excluded from the study if they don’t have a glucometer or obtain one 
during the course of the study.
During the screening visit, written informed consent to participate in the study will be obtained 
in person, or remotely via  PSH Teams, by the research coordinator. Informed consent will be 
obtained only after subjects are given sufficient information about the research, procedures and 
expectations, and the risks and benefits to reach an informed decision as to whether they will 
voluntarily participate. As MBSR could have potential adverse effects, subjects will be made 
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aware that the study treatment they are assigned to could have adverse effects, including 
increased depression, anxiety or panic, re-experiencing of traumatic memories (especially if 
there is a history of trauma or PTSD), dissociation, executive dysfunction, headaches/body pain 
and insomnia (Lindahl et al., 2017; Lomas et al., 2014; Cebolla et al., 2014; Brooker et al., 2013; 
Johnson et al., 2016; Reynolds et al., 2017; Britton et al., 2010). The subject will have the 
opportunity to interact with one of the study investigators, who reviews the eligibility criteria.
Subjects will be given a copy of the Class Schedule and Homework. This will list the dates and 
times for all the classes that they could be assigned to and the requirement of at least 25 to 30 
minutes of home practice per day for 6 out of 7 days per week. The research coordinator will 
verify that the subject is available for the intervention sessions with reasonable certainty. If a 
subject thinks they will miss the Orientation, or if they think they will miss more than 2 classes 
during the first 8 weeks (including Class #1 to 8 and the Retreat), they will be encouraged to wait 
for another wave/cohort when they are able to make the time commitment.
After obtaining informed consent, further screening will be completed during the screening visit 
(See Screening Assessments Form). Subjects will complete the Perceived Stress Scale-10 (PSS-10) 
questionnaire and need a score ≥ 12 to continue in the study. This cutoff is based on normative 
data from the U.S. population (Cohen & Williamson, 1988). The PSS-10 will be self-administered 
in REDCap and reviewed by the study coordinator for completeness.  REDCap will automatically 
calculate the PSS-10 score when subjects answer all items on the PSS-10. If any item of the PSS-
10 is intentionally skipped, a valid score cannot be calculated to assess inclusion criteria and the 
subject is ineligible to continue with the screening. 
Medical records, when available, will be reviewed to confirm that the subjects have diabetes 
and are eligible for the study.  
Demographics: Age (calculated from date of birth), Sex (male or female), Race and Ethnicity will 
be recorded at screening.
Screening Laboratory Exam: Subjects will present to the Penn State Clinical Research Center 
(CRC) for the screening visit. They will not need to fast for the screening visit. A maximum of 30 
mL of blood will be taken during the screening visit to assess hemoglobin A1c for eligibility. 
(Table 2). If the patient has a lab hemoglobin A1c within 12 weeks and 2 days (86 days) before 
the start of the study intervention (Orientation), these records may be obtained, and after 
verifying the hemoglobin A1c result in the outside records or the EMR, the hemoglobin A1c 
result can be accepted in lieu of repeating the test for screening. If the screening visit is being 
conducted remotely due to COVID-19, or due to the preference of the subject, and if a lab 
HbA1c value collected within the 12-week window is not available in their medical record, then 
the subject will be mailed a Home A1CNow Self Check kit, and sent instructions and a link to a 
video demonstration on how to perform the blood test. For subjects with the Penn State Health 
care region, who do not have an hemoglobin A1c in their EMR, they will be given the option to 
have a lab sample obtained at a Penn State Health center to assess hemoglobin A1c or have a 
Home A1CNow kit mailed to them.   The coordinator will observe and guide them through the 
appropriate collection steps during the ( PSH Teams) live videoconferencing screening visit. 
Subjects will communicate their home hemoglobin A1c test result to the study team by showing 
the research coordinator their home hemoglobin A1c result as displayed on their Home A1CNow 
Self Check kit during the (PSH Teams) live videoconferencing screening visit.
Pregnancy clinical criteria (history with pregnancy testing as indicated): As the study 
interventions pose no risk to a developing pregnancy, and the rationale for excluding pregnant 
women is that pregnancy may affect blood glucose, clinical criteria (history with pregnancy 
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testing as indicated) will be used for exclusion. There is minimal clinically relevant change in 
blood glucose in the early first trimester, lessening the potential impact of early pregnancy on 
study outcomes. For research purposes in this protocol, women are not considered of 
childbearing potential if they
(1)
Have completed menopause, defined as
a.
Age greater than 55 years old, OR
b.
Age 55 years or less and at least 12 months since last menstrual period, OR
c.
Age 55 years or less and at least 6 months since last menstrual period and 
FSH > 40 IU
(2)
Have had a surgical sterilization defined as 
a.
Hysterectomy and/or 
b.
Bilateral salpingectomy and/or 
c.
Bilateral oophorectomy 
(3)
Do not have a male partner who can father children; Male partners can be 
incapable of fathering children because of congenital anomalies, surgery, or 
medical treatment.
In all other women, pregnancy testing will not be indicated when there is reasonable certainty 
that the woman is not pregnant defined as meeting any one of the following criteria 
recommended by the CDC (CDC, 2021). These criteria have a negative predictive value of 99%–
100%, which means that they are highly accurate in ruling out pregnancy among women who 
are not pregnant. If a woman meets any one of these criteria, there is reasonable certainty that 
she is not pregnant, and a urine pregnancy test will not be indicated for the purpose of this 
study: 
•
is ≤7 days after the start of normal menses 
•
has not had sexual intercourse since the start of last normal menses 
•
has been correctly and consistently using a reliable method of contraception 
o
oral contraceptives
o
injectables
o
barrier methods
o
intrauterine device (IUD)
o
hormonal implant
o
hormonal ring/patch
o
bilateral tubal ligation 
o
partner with vasectomy 
•
is ≤7 days after spontaneous or induced abortion 
•
is within 4 weeks postpartum 
•
is fully or nearly fully breastfeeding (exclusively breastfeeding or the vast majority 
[≥85%] of feeds are breastfeeds), amenorrheic, and <6 months postpartum
If a woman does not meet at least one of the above criteria, then urine will be collected for a 
pregnancy test, and any subjects found to be pregnant will be informed of their pregnancy test 
results, and then excluded from the study due to the effects of pregnancy on study outcomes. If 
the subject has a pregnancy test within 2 weeks before the screening visit, documented in their 
medical records, these records may be obtained, and after verifying the pregnancy test result in 
the outside records or the EMR, the pregnancy test result can be accepted in lieu of repeating 
the test for screening. If the screening visit is conducted remotely, and if a pregnancy test result 
collected within 2 weeks before the screening visit is not available in the subject’s medical 
record, then the subject will be mailed a urine pregnancy test. Subjects will communicate their 
urine pregnancy test result to the study team by showing the research coordinator their 
pregnancy test result as displayed on their urine pregnancy test kit during the (PSH Teams) live 
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videoconferencing screening visit. Subjects found to be pregnant will be excluded from the 
study.
Screening Safety Questionnaire: Subjects will be screened for depression and suicidality using 
the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 will be self-administered in REDCap and 
reviewed by the research coordinator for completeness.
If a subject is not comfortable with answering the 9th item of the PHQ-9 at the screening 
visit, they will be excluded from the study. If a subject refuses to answer the 9th item of the PHQ-
9 at any of the subsequent study visits, the subject will be excluded from the study, and the 
research coordinator will immediately contact one of the below suicidality experts.
PHQ-9 scores will be calculated in REDCap, even if subjects refuse to answer all of the 
PHQ-9 questions. If a subject’s PHQ-9 score at any of the study visits is 10 or greater, they will be 
advised to see their PCP for further evaluation. The research coordinator will give the subject an 
Incidental Findings Letter to share with their PCP. This letter will include the subject’s PHQ-9 
score. These subjects can still continue in the study as long as they meet the other eligibility 
criteria.
If a subject scores 1 or greater on the 9th item of PHQ-9, the research coordinator will 
interview the subject using the modified P4 Screener to assess suicide risk (Dube et al., 2010). If 
the subject answers ‘Somewhat Likely’ or ‘Very Likely’ to the modified P4 Screener question 
which asks “How likely do you think it is that you will act on these thoughts about hurting 
yourself or ending your life some time over the next month?”, they are considered higher risk 
and will not be eligible for the study. For these higher risk subjects, the research coordinator will 
immediately contact one of the following appropriate suicidality experts to initiate a psychiatric 
consultation:
1.
Dr. Dahlia Mukherjee (cell 775-351-9927)
2.
Dr. Erika Saunders (pager 2292, cell 717-514-3818)
3.
Other personnel available for an immediate Psychiatric consult  
If on the modified P4 Screener, the subject answers ‘Not at all Likely’ to “How likely do 
you think it is that you will act on these thoughts about hurting yourself or ending your life some 
time over the next month?” and they answer ‘No’ to “Is there anything that would prevent or 
keep you from harming yourself?”, a follow-up prompt is triggered “What is preventing you 
from acting on harming yourself?” If the subject provides a response, they are eligible to 
continue in the study as long as they meet the other eligibility criteria. If the subject 
cannot/does not provide a response, the subject will be considered higher risk and will be 
excluded from the study. The research coordinator will immediately contact one of the above 
suicidality experts.
MINI structured interview: Screening will also include the MINI International Neuropsychiatric 
Interview (MINI) Version 7.0.2., which is a brief structured interview for the major psychiatric 
disorders in DSM-V and ICD-10 (Sheehan et al., 1998; Sheehan et al, 1997; Lecrubier et al., 1997; 
Amorim et al., 1998). The MINI assesses for the 17 most common disorders in mental health 
that are the most important to identify in clinical and research settings. MINI interviews will be 
conducted by a trained research coordinator under the supervision of a clinical psychologist (Dr. 
Mukherjee) to screen patients for psychiatric conditions. 
The MINI will be used for research purposes to document whether subjects meet 
criteria for psychiatric conditions, not to make any clinical diagnoses. Subjects will not be 
informed of the results of their MINI. If the MINI indicates that the subject meets criteria for any 
of the excluded conditions (See Exclusion Criteria above), the subject will not be eligible for the 
study. All excluded subjects will be given a list of General Resources for diabetes and mental 
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health so as not to imply the reasons for which they were excluded from the study. This list will 
be mailed to excluded subjects when screening visits are completed remotely.
Section B of the MINI, which screens for suicidality, will not be completed as subjects 
will have already been screened for suicidality with the PHQ-9 and if indicated the modified P4 
Screener as described above. 
The MINI Summary and select outcomes from the body of the MINI (e.g. Severity of 
Binge-Eating Disorder) will be entered into REDCap by the study coordinator. These results will 
be used to characterize the study population.
The completed paper MINI will be kept in the subject’s study folder.
Participating in this research study will not deny any appropriate medical care or mental health 
care subjects would ordinarily receive from their PCP, mental health provider, or other health 
care providers. Names and doses of both diabetes and psychiatric medications will be collected 
throughout the study. 
At the end of the screening visit, if the subject remains eligible to continue in the study, the 
subject will be scheduled for a baseline study visit and the following additional procedures will 
be completed at the screening visit:

The research coordinator will ensure that the dates and times on the subject’s diabetes 
devices (glucometers, CGM, insulin pump and other smart insulin delivery devices) are 
correct in anticipation of collecting data from these devices at the subsequent study 
visits. The research coordinator will record the date and time that are on each device.  If 
the date or time on a device are not correct, the research coordinator will record the 
device date and time offset, and work with the subject to correct the date and time on 
the device. This will be repeated at each of the subsequent study visits. If study visits are 
conducted remotely, subjects will be asked to communicate the dates, times and other 
data on their diabetes devices to the study team by sharing their diabetes device data 
remotely (by uploading or connecting their diabetes device data to secure, cloud-based 
diabetes management systems such as Dexcom Clarity and LibreView as done in routine 
clinical care), by sharing reports of their diabetes device data, by showing the the study 
team their diabetes device displays or reports during the remote (PSH Teams) live 
videoconferencing study visit, or by self-reporting their diabetes device data via a phone 
call after the study visit. If the date or time on a device are not correct, the research 
coordinator will record the device date and time offset, and work with the subject to 
correct the date and time on the device during the remote (PSH Teams) live 
videoconferencing study visit. This will be repeated at each of the subsequent study 
visits.

Subjects will complete a Phone Call Time Preference questionnaire in REDCap indicating 
their preferred windows of time to receive phone calls for visits and scheduling 
appointments. Subjects will be instructed that 3-hour windows of time are preferable 
(e.g. 6-9 PM on Wednesdays is better as it allows for more flexibility than 8-9AM, 1-
2PM, and 5-6PM). Subjects will complete this questionnaire at the screening, baseline 
and 2-month study visits.

If the subject does not have a working glucometer, a letter will be sent to their primary 
care provider, PCP, asking them to prescribe a glucometer for the patient, and to refer 
the patient to a diabetes educator for glucometer teaching if the patient has never used 
a glucometer before. This is being done because it is the standard of care for patients 
with uncontrolled diabetes, and it is important to collect subjects’ historical blood 
glucose levels for data analysis, before and after the study stress reduction sessions. 
Subjects will be able to obtain a glucometer with their physician’s prescription, and get 
the necessary education on its use. If the subject has had a glucometer previously and 
does not have one now for any reason (e.g. they lost it, broke it, etc.), they will be 
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offered a sample glucometer kit (if available), and advised to check with their insurance 
regarding coverage of additional glucometer testing supplies (e.g. test strips and 
lancets), and to see their PCP for prescriptions for additional glucometer testing 
supplies. The research coordinator will work with the subject to ensure that the correct 
date and time are set on the sample glucometer they are given. Subjects will be asked to 
bring their sample glucometer to their subsequent remote or in-person study visits so 
that data can be collected from them. Subjects paying out of pocket for glucometer 
testing supplies will be advised to consider Walmart’s ReliOn brand testing supplies 
which are more affordable. This will be repeated at the baseline and 2-month study 
visits, when applicable. Subjects will NOT be excluded from the study if they don’t have 
a glucometer or obtain one during the course of the study.

Subjects will be given information about the optional 24-hour diet recall surveys they 
will be invited to complete during the 2 weeks before Class #1, 2 weeks after Class #8, 
and 2 weeks before Booster #4. Dietary intake data for 24-hour recalls will be collected 
and analyzed using the Automated Self-Administered 24-hour (ASA24) Dietary 
Assessment Tool, version 2020 and version 2022, developed by the National Cancer 
Institute, Bethesda, MD (https://epi.grants.cancer.gov/asa24). The research coordinator 
will send subjects unannounced emails with a link to complete their 24- hour diet recall 
on the ASA24 website. The emails will be sent during the specified time windows to 
collect 24-hour diet recall data for 1 weekday and 1 weekend around the baseline, 2-
month and 6-month study visits. 

The subject will be given or mailed the Baseline Medical History questionnaire to 
complete at home. They will complete this electronically or on paper. If they complete a 
paper form, they will be asked to mail it back. They can also bring the paper form to 
their baseline visit if it is being done in the CRC. 

The subject will be given written instructions and reminders for their baseline study 
visit.
 
Table 2. Screening assessments 
Inclusion/Exclusion assessments
Safety assessments
-Hemoglobin A1c ≥ 7.5%
-Pregnancy clinical criteria with pregnancy testing as indicated 
(in females age 55 years old or younger)
-Perceived Stress Scale-10 score ≥ 12 
-PHQ-9
-modified P4 Screener if 9th item of 
PHQ-9 is 1 or greater
-MINI structured interview
Overview of Study Visit Time Windows (See Table 3): The screening visit will be scheduled within 
10 weeks and 2 days (72 days) before the start of the study intervention (Orientation session). 
The baseline study visit will be scheduled within 6 weeks and 2 days (44 days) before the 
Orientation session (to allow for sufficient time for scheduling around holidays). Randomization 
will take place during the week before the Orientation session. Class #1 (the first class after 
Orientation) will start ~1 week after the Orientation session. The follow-up phone call will be 
scheduled within the 2 weeks after Class #4. The 2-month study visit will be scheduled within 
the 4 weeks immediately after Class #8 (the end of the 8-week MBSR or SME program). The 6-
month study visit will be scheduled within the 4 weeks immediately after Booster session #4. 
The time windows for capturing the optional 24-hour diet recall data are within 2 weeks before 
Class #1, 2 weeks after Class #8, and 2 weeks before Booster #4. The time windows for capturing 
the optional Actigraph data are +/- 2 weeks of the baseline and 2-month study visits, and in the 
4 weeks before the 6-month study visit.
It is possible that a subject completes the screening visit, or the screening and baseline 
visits, for a cohort and then is unable to be randomized to that cohort and needs to wait to be 
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randomized to a later cohort (due to reaching the maximum number of participants permitted 
in a class, or due to the subject not being reached in time for randomization, or due to the 
subject requesting to participate in a later cohort when they will be more available). In these 
scenarios, the screening and baseline visits will need to be repeated if they fall outside of the 
Study Visit Windows for the new later cohort. In other words, the screening visit will need to be 
repeated if it is more than 10 weeks and 2 days (72 days) before the new later Orientation 
session, and the baseline visit will need to be repeated if it is more than 6 weeks before the new 
later Orientation session. Subjects will need to attend the screening visit and baseline visit 
within the specified time window in order to be randomized. In these instances, all data from 
screens and visits that were collected during times when the subject was not randomized will be 
maintained. However, only the screening and baseline data provided by the subject within the 
specified time windows will be used in analysis. Data collected from earlier duplicate screens 
will be maintained and documented securely in REDCap, therefore it is possible that multiple 
study ID numbers correspond to one randomized subject. 
The research coordinator will make 3 attempts to reach a subject for the follow-up 
phone call within the 2 weeks after Class #4. If a subject misses the follow-up phone call within 
this specified 2-week time window, the subject will not be withdrawn from the study, and their 
follow-up phone call data will be considered missing data. If a subject misses the 2-month study 
visit within the specified time window, the research coordinator will contact them and if the 
subject confirms that they are willing to come in for the final 6-month study visit, the subject 
will not be withdrawn from the study and their 2-month study visit data will be considered 
missing data. 
Lost to Follow-up: Subjects will be withdrawn from the study and considered lost to follow-up if 
they cannot be reached after doing the following:
●   First, the research coordinator will call and e-mail the subject once a week for 3 weeks. 
●   If no response, then the research coordinator will make 3 attempts to call their emergency 
contact if they provided an emergency contact. Subjects will be asked to provide an emergency 
contact at the screening visit in case we cannot reach them because they moved, are in a 
hospital, etc. The emergency contact is usually someone that does not live with them, or at least 
someone with a different phone number.
This process will be initiated when the subject has not shown up to a study visit. If no 
response is received from the subject within 60 days of missing the study visit, the subject will 
be withdrawn from the study and considered lost to follow-up. 
Drop outs/Treatment failures:  Dropouts may occur due to participant choice or physician 
recommendation for reasons such as adverse effects, poor compliance, etc. 
If a subject is randomized but misses Orientation, the instructors may offer the subject 
an individual Orientation session. If the subject is unable to complete Orientation before Class 
#2 after being randomized, they will not be permitted to continue in the study.
As soon as a subject is determined to be Lost to Follow-up, Withdrawn or Completed, all 
data collection will cease after collecting reasons for participant-initiated withdrawal on the 
Attrition Survey. The date a subject is no longer considered part of the study will be 
documented in an End of Trial form.
Attrition Information: CONSORT guidelines require a reason for dropout for every subject, and 
whether the reason was due to an adverse event. The research coordinator will collect attrition 
information for each dropout from the study, and record the dropout date, subjects’ responses 
to Yes/No questions about general reasons for attrition that do not reveal the subjects’ group 
assignment, and whether the dropout is Subject-initiated or Investigator-initiated. 
If it is a Subject-initiated dropout or a lost to follow-up, the subject will be e-mailed a 
link to a REDCap Participant-Completed Attrition Information Survey consisting of one open 
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ended question to elicit feedback about their experience in the study and learn more about 
their reasons for not continuing in the study. As subjects’ responses could reveal group 
assignment, the research coordinator and other blinded study team members will be blinded to 
subjects’ responses to this survey in REDCap.
Investigator-initiated withdrawals: A subject may also be withdrawn from the study 
and/or intervention by the investigator. In this case, the research coordinator will record the 
reasons why the investigator withdrew the subject from the study (See DSMP). 
7.2.3
Visit #1 (Baseline Study Visit) 
Enrolled subjects who meet the eligibility criteria at the screening visit will be invited to 
schedule a baseline study visit at the CRC. If the baseline visit cannot be completed in the CRC 
due to COVID-19, or the preference of the subject, the baseline visit will be completed remotely 
using videoconferencing (PSH Teams), and all data that can be collected remotely will be 
obtained, including the home hemoglobin A1c using the Home A1CNow Self Check kit, urine 
pregnancy test when applicable, diabetes device data, and surveys. The subject will not 
participate in hair, nail or saliva collection if visits are remote. The baseline visit will last 
approximately 3 hours. The baseline visit will be scheduled within 6 weeks prior to the planned 
start of the study intervention (Orientation session). Eligible subjects who complete the baseline 
visit can undergo randomization and subsequently attend Orientation. Hemoglobin A1c and 
Perceived Stress Scale-10 assessments will be repeated at the baseline visit, however subjects 
will not be excluded at baseline based on the results. The MINI will not be repeated at baseline. 
Subjects will need to continue to meet the rest of the Inclusion/Exclusion criteria at the baseline 
visit to be able to continue in the study.  An overview of the study procedures is found in Table 
3.
Subjects will be asked to provide the following for their remote or in-person baseline visit:

The completed Baseline Medical History questionnaire they were given at the screening 
visit; They will complete this electronically or on paper. If they complete a paper form, 
they will be asked to mail it back. They can also bring the paper form to their baseline 
visit if it is being done in the CRC. 

A list of their current medications and dietary supplements so their current medications 
and supplements can be recorded 

Their smartphone, if they have one

Their diabetes devices (glucometers, CGM, insulin pump and other smart insulin delivery 
devices) 

Home A1cNow Self Check Kit if provided one at screening
The subjects will present to the baseline visit in the CRC in a 10-hour fasting state (no food or 
drink, except for water). Additionally, subjects will be instructed not to eat or drink (except for 
water), chew gum, smoke, brush their teeth, exercise physically, or consume prescription or 
over-the-counter medications in the 60 minutes prior to their baseline visit (as well as during the 
last 60 minutes of their baseline visit) as we will be collecting saliva samples 1) Just before the 
study visit starts, and 2) immediately after the study visit ends. If subject forgets to fast, blood 
will still be drawn and documentation will be made of how many hours it has been since they 
last had something to eat or drink.
Subjects will be instructed not to wash their hair for 24 hours before their study visit in the CRC 
and not to have their hair cut to a length less than 2 cm (as we will be collecting optional 2 cm 
hair samples weighing at least 10 mg to assess cortisol levels over the past 2 months). Subjects 
may opt-out of this procedure and will still be permitted to continue in the study. Subjects will 
be instructed not to clip their fingernails for at least 2-3 weeks prior to their study visit to allow 
for the optional clipping of approximately 2 mm of nails from each finger of both hands. 
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Subjects will be instructed to remove any nail polish at least 24 hours before their study visit. 
Subjects may opt-out of this procedure and will still be permitted to continue in the study. 
At the baseline visit, subjects will be given another copy of the Class Schedule and Homework. 
The research coordinator will verify that the subject continues to be available for the 
intervention sessions with reasonable certainty. If a subject thinks they will miss the Orientation, 
or if they think they will miss more than 2 classes during the first 8 weeks (including Class #1 to 8 
and the Retreat), they will be encouraged to wait for another wave/cohort when they are able 
to make the time commitment.
The research coordinator will obtain baseline measures including saliva, blood, hair (optional), 
and nail (optional) samples for hormonal and metabolic parameters, and a brief physical exam if 
the baseline study visit is in the CRC.
Self-administered questionnaires will be directly entered into REDCap by all subjects and 
reviewed by the research coordinator for completeness. Data will be collected from subjects’ 
diabetes devices (glucometers, CGM, insulin pump and other smart insulin delivery devices) if 
they use these devices. 
At the baseline visit, a urine pregnancy test will be administered to female subjects of 
childbearing potential who do not meet any of the criteria for reasonable certainty of not being 
pregnant as defined above in the screening visit. Any subjects found to be pregnant will be 
informed of their pregnancy test results, and then withdrawn from the study due to the effects 
of pregnancy on study outcomes. If the subject has a pregnancy test within 2 weeks before the 
baseline visit, documented in their screening visit or verified in their medical records, the 
pregnancy test result can be accepted in lieu of repeating the test at baseline. If the study visit is 
conducted remotely, and if a pregnancy test result collected within 2 weeks before the study 
visit is not available, then the subject will be mailed a urine pregnancy test to complete at this 
visit. Subjects will communicate their urine pregnancy test result to the study team by showing 
the research coordinator their pregnancy test result as displayed on their urine pregnancy test 
kit during the (PSH Teams) live videoconferencing study visit. If the pregnancy test is positive, 
the subject will be withdrawn from the study. 
Subjects will be given a Home A1CNow Self Check kit at baseline, or if they received a kit at 
screening they will be asked to bring the kit to their remote or in-person baseline visit. If the 
baseline study visit is conducted remotely, subjects will be mailed the Home A1cNow Self Check 
Kit. The research coordinator will review procedures and watch instructional videos with 
subjects, and assist the subjects in obtaining their hemoglobin A1C value from the kit. Subjects 
who complete their baseline study visit in the CRC will bring this kit home in case, for any 
reason, they are not able to return to the CRC for their 2 month and 6 month visit so that they 
will be able to collect their hemoglobin A1C results at home as this is the primary outcome for 
this study. If the 2 month and 6 month visits are being conducted at the CRC, the subjects will be 
asked to bring their Home A1CNow Self Check kit to the CRC and the kit will be used to collect 
their home hemoglobin A1c, in addition to the blood draw for hemoglobin A1c. The Home 
A1cNow Self Check Kit contains step by step instructions for subjects to reference for future 
testing. 
If the subject opts-in to wearing an Actigraph device, the subject will be given an Actigraph 
device to wear around their waist for 7 days after the baseline visit.  If the study visit is 
conducted remotely, the subject will be mailed the Actigraph device, with a stamped envelope 
to return after the required wear time.
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Table 3. Overview of Study Procedures and Measurements
Study Procedures
Pre-
Screen-
ing 
Phone 
Call
Study
Visit #0
Screening
Study Visit 
#1 
Baseline
Random-
ization 
Phone Call
Start Class 
#1 of 8-wk 
MBSR or 
SME
 Study 
Visit #2 
/Follow-
up 
Phone 
Call
Study 
Visit #3
MBSR or 
SME 
Booster 
sessions
Study 
Visit #4
(End of 
study)
Timeline 
Within 10 
wks before 
Orientation
Within 6 
wks before 
Orientation  
Within 1 wk 
before  
Orientation 
~1 wk after 
Orientation
Within 2 
wks after 
Class #4
After 
Class 
#8 
(2 
months)
Once a 
month for 
4 months 
After 
Booster 
#4 
(6 
months)
Phone or In-person 
Intake Pre-Screen 
x
Written Informed 
Consent
x
Class Schedule & 
Homework- Verify 
subject availability
x
x
x
MINI structured 
interview
x
Screening 
Assessments 
x
x
Phone Call Time 
Preference
x
x
x
Orientation 
Questionnaire
x
Stress Reduction 
Expectancy Scale 
(SRES)
x
x
x
Baseline Medical 
History 
x
Medications
x
x
x
Stress & Cravings 
Surveys
x
x
x
x
x
x
x
Daily Diary Surveys
x
Start-up after 
Class #1
x
x
x
x
GLUCOSE CONTROL AND OTHER PHYSIOLOGIC OUTCOMES
Primary Outcome: 
Hemoglobin A1ca 
x
Lab or 
Home Kit
x
Lab & Home 
Kit
x
Lab & 
Home 
Kit
x
Lab & 
Home 
Kit
Fasting Glucose 
x
x
x
Glucometer/CGM/
insulin pump data 
Date/Time 
check only
x
x
x
C-peptide 
(for HOMA-IR)
x
x
x
Fasting Lipids, 
hsCRP & TNF-α
x
x
x
Saliva cortisol & 
α-amylase
x
x
x
Blood pressure & 
Heart rate 
x
x
x
Weight, Height, and 
Waist and Hip 
Circumference
x
x
x
Body composition 
(Tanita scale 
measurements only – 
if in CRC)
x
x
x
Hair and nail samples 
(optional)
x
x
x
Urine pregnancy test
x
x
x
x 
Hypoglycemia Survey 
x
x
x
x
BEHAVIORAL OUTCOMES
24-hour dietary 
recalls (optional)
x
x
x
Food Craving 
Questionnaire-Trait 
Reduced
x
x
x
Walking Enjoyment 
x
x
x
Accelerometer data 
(optional)
x
x
x
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Adherence to 
diabetes medications 
(Participant 
Questionnaire)
x
x
x
Counterfactual 
Measurement
x
x
PSYCHOSOCIAL OUTCOMES
Toronto Mindfulness 
Scale (TMS)
x
x
x
Perceived Efficacy, 
Satisfaction, 
Engagement & 
Confidence 
x
x
Diabetes Distress 
Scale
x
x
x
Perceived Stress 
Scale-10 (PSS-10)
x
x
x
x
Short Form-12 (SF-
12)
x
x
x
Positive and Negative 
Affect (PANAS)
x
x
x
BRFSS (ACE survey)
x
Childhood Trauma 
(CTQ)
x
Modified Coronavirus 
Impact Scale
x
x
x
GAD-7
x
x
x
PROMIS Sleep 
Disturbance 8a
x
x
x
Safety screens 
(PHQ-9, and if 
indicated modified P4 
Screener) 
x
x
x
x
Stress Experience 
Survey
x
x
x
x
a Screening hemoglobin A1c: If the patient has a lab hemoglobin A1c result within 12 weeks and 
2 days (86 days) before the start of the study intervention (Orientation), these records may be 
obtained, and after verifying the lab hemoglobin A1c result in the outside records or the EMR, 
the lab hemoglobin A1c result can be accepted in lieu of repeating the test for screening. If the 
patient does not have a lab hemoglobin A1c result within 12 weeks and 2 days (86 days) before 
the start of the study intervention, the screening hemoglobin A1c result will be obtained from 
either the Hershey Clinical Lab (if the screening visit is conducted in person), or from a Home 
A1cNow Self Check Kit (if the screening visit is conducted remotely). 
In-person baseline, 2-month, and 6-month study visit hemoglobin A1c: When the 
baseline, 2-month, and 6-month study visits are conducted in person, hemoglobin A1c results 
will be obtained from both the Hershey Clinical Lab and from the Home A1cNow Self Check Kit. 
A lab hemoglobin A1c result obtained from the Hershey Clinical Lab within 2 weeks before the 
visit can be accepted as the study visit lab hemoglobin A1c. A screening Home A1cNow Self 
Check Kit hemoglobin A1c result within 2 weeks before the baseline visit can be accepted as the 
baseline home hemoglobin A1c.
Remote baseline, 2-month, and 6-month study visit hemoglobin A1c: When the baseline, 
2-month, and 6-month study visits are conducted remotely, home hemoglobin A1c will be 
collected using the Home A1cNow Self Check Kit. A screening Home A1cNow Self Check Kit 
hemoglobin A1c result within 2 weeks before the baseline visit can be accepted as the baseline 
home hemoglobin A1c. If the subject has a lab result (e.g. lab hemoglobin A1c) outside of the 
study, the lab result (e.g. lab hemoglobin A1c) will be recorded as the study visit lab result (e.g. 
lab hemoglobin A1c) after verifying the result in outside records or the EMR.
Missed 2-month and 6-month (in-person or remote) study visits: If the subject misses 
their 2-month or 6-month study visit, and has a lab result (e.g. lab hemoglobin A1c) outside of 
the study, the lab result (e.g. lab hemoglobin A1c) will be recorded as the study visit lab result 
(e.g. lab hemoglobin A1c) after verifying the result in outside records or the EMR.
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All subjects will be given the same general written guidelines on diet and exercise at the 
baseline visit, which will consist of two handouts downloaded from the American Diabetes 
Association Patient Education Library: (1) “Plan Your Portions” Diabetes Placemat  and (2) “The 
Diabetes Advisor - Physical Activity.” All subjects will also be given handouts on Hyperglycemia 
and Hypoglycemia, as well as Glucometer Best Practices and Blood Glucose Meter Correlation, 
at the baseline visit. This will be the only information that will be the same across both groups. 
The MBSR group will not receive any additional health education other than these handouts.
Baseline Laboratory Exam:  
Subjects will present to the baseline study visit in the CRC after a 10-hour fast (no food or drink, 
except for water) for collection of a single sample of blood. Additionally, subjects will be 
instructed not to eat or drink (except for water), chew gum, smoke, brush their teeth, exercise 
physically, or consume prescription or over-the-counter medications 60 minutes prior to 
presenting for their baseline study visit (as well as during the last 60 minutes of their baseline 
visit) to allow for collection of saliva samples. 
In the fasting state, the research coordinator and/or CRC staff will collect a single blood 
sample of approximately 60 mL from each subject in order to measure hemoglobin A1c, glucose, 
c-peptide, lipid panel, high sensitive C-reactive protein (hsCRP), and TNF-α. The fasting glucose 
and c-peptide will be used to calculate the Homeostatic index of insulin resistance (HOMA-IR). 
The blood draw for hemoglobin A1c will be in a lavender top tube (whole blood sample). 
The hemoglobin A1c assay must be run immediately by the Hershey Clinical Lab, however 
subjects will not be excluded based on their baseline lab hemoglobin A1c. A lab hemoglobin A1c 
result obtained from the Hershey Clinical Lab within 2 weeks before the baseline visit can be 
accepted as the baseline lab hemoglobin A1c, otherwise a lab hemoglobin A1c from the Hershey 
Clinical Lab will be obtained at in-person baseline study visits. 
The samples for glucose, lipid panel and hsCRP will also be run immediately. Blood 
samples for c-peptide and TNF-α will be frozen at -80⁰C. The c-peptide samples will be collected 
in a green top with heparinized plasma and stored to be analyzed later under this protocol. The 
TNF-α samples will be stored to be analyzed later, but they will not be analyzed under this 
protocol. Validated assays with intra- and inter-assay coefficients of variation less than 15% will 
be used. 
Within 5 minutes of having their blood drawn, subjects will be asked to check their 
glucose level via finger stick on their glucometer (optional), and via their continuous glucose 
monitor (if they have one).  Research staff will compare glucose readings from the different 
sources to assess accuracy and calibration of subjects’ devices. The research staff will notify 
subjects of discrepancies once lab reference glucose results are obtained, and advise subjects to 
refer to the Glucometer Best Practices and Blood Glucose Meter Correlation handout they were 
given at their baseline visit. Accuracy of glucometer will be defined as within 15% of lab 
reference value if > 100 mg/dL, or within 15 mg/dl of lab reference value if < 100 mg/dL (Klonoff 
et al., 2018). This is recommended when reporting glucose data in clinical research (Schnell et 
al., 2015). Glucometer brand and sub brand, test strip brand, and other important information 
regarding how subjects are using their diabetes devices will also be collected.
All of these laboratory assessments will be obtained at the baseline visit, 2-month visit 
and 6-month visit. If a study visit is conducted remotely, or if a subject misses a study visit, the 
research coordinator will obtain and record any available outside lab results, including 
hemoglobin A1c, glucose, and Lipid panel. 
Home A1cNow Self Check Kit (in-person and remote study visits):
All subjects will be asked to perform a home hemoglobin A1c test using the Home 
A1cNow Self Check Kit at baseline, 2-month, and 6-month (in-person or remote) study visits. A 
screening Home A1cNow Self Check Kit hemoglobin A1c result within 2 weeks before the 
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baseline visit can be accepted as the baseline home hemoglobin A1c, otherwise a Home 
A1cNow Self Check Kit hemoglobin A1c will be collected at the baseline visit. Subjects will not be 
excluded based on their baseline home hemoglobin A1c. 
Salivary collection procedure (in-person study visits): Saliva will be collected for cortisol and α-
amylase at the baseline study visit (and also at the 2-month and 6-month study visits). At each 
study visit, the research coordinator will collect 2 saliva samples: 1) Just before the study visit 
starts, and 2) immediately after the study visit ends. Given the diurnal variation of salivary 
cortisol and α-amylase, it will be important that time-of-day of the study visits is consistent 
within each subject, although this will not always be feasible to implement due to scheduling 
logistics. Saliva will not be collected from subjects if study visits are conducted remotely.
Subjects will be instructed not to eat or drink (except for water), chew gum, smoke, 
brush their teeth, exercise physically, or consume prescription or over-the-counter medications 
60 minutes prior to sample collection. The research coordinator will follow the written step-by-
step Salivary Cortisol Collection Instructions to collect whole saliva samples from the subjects 
using the gold standard passive drool method. The saliva collecting equipment (Salimetrics, 
State College, PA) will consist of a saliva collection aid (SCA) and cryovials. Cryovials will be pre-
labeled with the subject number, study visit (baseline, 2-month, and 6-month) and sample 
number (S1, S2) using freeze resistant labels. When collecting a saliva sample, the research 
coordinator will instruct the subjects to allow saliva to pool in their mouth.  Then with their 
head tilted forward, gently guide the saliva through the SCA into the cryovial, and fill it to the 
required volume. The samples will be stored in secured -80⁰C freezers at the Penn State 
Institute for Personalized Medicine. The saliva samples will be stored to be analyzed later for 
cortisol, α-amylase and other parameters, but they will not be analyzed under this protocol. 
The research coordinator will complete the Saliva Cortisol Collection Questionnaire in 
REDCap, recording the date and time when each sample was taken, and subjects’ responses to 
questions about consumption of food or drink, alcohol, caffeine, gum, and prescription and 
over-the-counter medications, brushing their teeth, exercise activities, dental work, and 
problems with their gums, teeth or mouth around the time of each sampling. The research 
coordinator will also complete the Steroid Medication Questionnaire (included in the Visit 
Questionnaire) and record any steroid medications subjects are currently taking including 
steroid skin creams, ointments and injections. 
Hair and nail samples (optional protocol procedures for in-person study visits) will be collected 
by the research coordinator at the baseline study visit (and also at the 2-month and 6-month 
study visits). Hair and nail samples will be stored to be analyzed later for cortisol and other 
hormonal and metabolic parameters, but they will not be analyzed under this protocol. Hair and 
nail samples will not be collected from subjects if study visits are conducted remotely.
Subjects who consent to collection of hair and nail samples will respond to questions 
about their hair and nail care as part of the self-administered Participant Questionnaire in 
REDCap, including questions about their hair washing, use of hair products, swimming in a 
chlorine pool, whether they typically exercise 2 or more hours per day, habitual nail-biting, use 
of nail polish or other fingernail treatments, etc.
There are several reasons for measuring cortisol in saliva, hair and nail samples. Saliva 
cortisol is a physiological measure of acute stress, whereas hair and nail cortisol are more 
integrated physiological measures of hypothalamic-pituitary-adrenocortical (HPA) activity and 
thus reflect chronic stress exposure (Meyer et al., 2014; Hodes et al., 2017). The stress hormone 
cortisol is gradually incorporated into the growing hair shaft. As human scalp hair grows on 
average 1 centimeter per month, cortisol levels obtained from hair segments several 
centimeters in length is a validated biomarker of stress experienced over a few months. A 
second reason to measure hair cortisol in our study is that hair cortisol has been linked with 
obesity, which is a common comorbidity of diabetes (Jackson et al., 2017). Finally, a preliminary 
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study suggests that mindfulness training may decrease hair cortisol levels in smokers (Goldberg 
et al., 2014).    
Assessment of cortisol levels in nail samples is another potential biomarker of chronic 
stress. The importance of also measuring cortisol in nail samples is that it represents a different 
timeline of hormone incorporation than scalp hair, and it can be obtained from subjects who 
lack scalp hair or from subjects in whom scalp hair is not available for other reasons (Doan et al., 
2018).
Leftover blood, saliva, hair and nail samples: If subjects agree, their leftover blood, saliva, hair 
and nail samples will be stored and used for future research studies. These future studies may 
provide additional information about the biological factors associated with variability in the 
response to MBSR in patients with diabetes, which could increase our understanding of the 
mechanisms underlying the variability and also inform the development of more personalized 
mindfulness-based interventions for diabetes. Dr. Raja-Khan will determine how the samples 
may be used or shared.  The leftover samples will be labeled with a code number only and 
stored in secured -80⁰C freezers in the Penn State Institute for Personalized Medicine. Subjects 
who change their mind about the storage of their leftover samples will contact Dr. Raja-Khan in 
writing in order to withdraw their permission. If they withdraw their permission, the samples 
will be destroyed.
Baseline Physical Exam: 
A brief physical exam will be performed on all subjects who have an in-person study visit at the 
CRC with the collection of the following measures by the research coordinator while subjects are 
dressed in light clothing without socks or shoes: 

Height recorded to the nearest 0.1 cm

A Tanita scale will be used to record weight to the nearest 0.1 kg, body mass index (BMI) in 
kg/m2, and body composition (Percent Body Fat, Fat Mass, Fat Free Mass, Basal Metabolic 
Rate, etc.) using advanced bioelectric impedance analysis technology (Ritchie et al., 2005). A 
data validation check will be performed in REDCap verifying that the BMI recorded from the 
Tanita scale is valid compared with the BMI calculated by REDCap from the subject’s 
recorded weight and height. If the subject has an electronic medical implant such as a 
pacemaker, the Tanita scale will not be used because the electrical signal traveling through 
the body may interfere with the operation of an electronic medical implant. In this scenario, 
or if a printout from the Tanita scale cannot be obtained,  a regular scale will be used to 
record the subject’s weight in kg, and the BMI will be calculated in REDCap. The Tanita scale 
can be safely used during pregnancy, but it will not give an accurate reading.

Waist and hip circumferences will be recorded to the nearest 1 cm. Waist will be measured 
at the level of the umbilicus and hip circumference will be measured at the widest diameter. 
Waist to hip ratio (WHR) will be calculated in REDCap. 

Blood pressure will be determined in the right arm after resting in a seated position for at 
least 5 minutes. A large cuff will be used when necessary. Three separate systolic and 
diastolic blood pressure measurements will be obtained and recorded at least 1 minute 
apart and averaged in accordance with American Heart Association (AHA) recommendations 
(Pickering et al., 2005). Mean arterial pressure (MAP) will be calculated as 2/3 mean 
diastolic blood pressure + 1/3 mean systolic blood pressure. Pulse will also be recorded. 
(This physical exam will be repeated at the 2-month visit and 6-month visit ). If the visit is 
conducted remotely, these measures will be collected from medical records and/or from 
subjects’ self-report. 
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Medications: 
Subjects will be asked to bring their current medication list to the remote or in-person baseline 
study visit (as well as to the subsequent 2-month and 6-month study visits). The research 
coordinator will record the names and doses of all current medications and supplements and 
whether medications or supplements were changed, started, or stopped during the study. If the 
participant does not bring their current medication list, their current medications will be 
obtained from their medical records.
Baseline Questionnaires: 
The Baseline Medical History questionnaire will be given or mailed to subjects at the 
screening visit to be completed at home since many of the questions about hospitalizations and 
family history may need to be researched by the subject for accuracy. Subjects will complete the 
Baseline Medical History questionnaire electronically or on paper. If they complete a paper 
form, they will be asked to mail it back. They can also bring the paper form to their baseline visit 
if it is being done in the CRC. The Baseline Medical History questionnaire will ask about the 
presence of diabetes complications and co-morbidities (retinopathy, neuropathy, nephropathy, 
high blood pressure, high cholesterol, heart attack, stroke, etc.), as well as about any 
hospitalizations or ER visits over the past 2 years. The following will also be collected at baseline: 
Type of diabetes, Number of years with diagnosed diabetes, Insulin treated vs. non-insulin 
treated, Marital status, Work status, Education, and Income. The research coordinator will 
review the Baseline Medical History questionnaire for completeness. If any answers are missing, 
the research coordinator will ask the subject: “Are you sure you meant to skip this question?” If 
the subject did not mean to skip the question, the research coordinator will record the subject’s 
response. 
 Medical records will be reviewed at baseline (and throughout the study) to confirm 
reasons for any hospitalizations and/or ER visits whenever applicable, as well as to confirm any 
new major diagnoses subjects report during the study. Adverse Event Reports will be completed 
when indicated. 
At the baseline visit, all subjects will complete the Orientation Questionnaire, which will 
be available to the MBSR and SME instructors in REDCap as they need this information for 
Orientation purposes. 
The Behavioral Risk Factor Surveillance System (BRFSS) Adverse Childhood Experience 
(ACE) and the Childhood Trauma Questionnaire (CTQ) will be assessed at baseline only (Felitti et 
al, 1998; Dube et al, 2001; Bynum et al., 2009; WHO, 2018; CDC, 2020a; CDC, 2020b).  ACEs are a 
risk factor for chronic disease, and there is preliminary evidence that people with more ACEs 
benefit more from mindfulness (Williams et al., 2014; Korotana et al., 2016). Four ACE scores 
will be calculated:
1-
BRFSS ACE score of 0 to 8 will be calculated using the 11 questions that are in 
the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System 
(BRFSS) ACE module. 
2-
Modified BRFSS ACE score of 0 to 8 will be calculated. This includes one 
additional question from the World Health Organization Adverse Childhood Experiences 
International Questionnaire (WHO ACE-IQ) about parental death which is incorporated into the 
parental separation or divorce category.
3-
CDC-Kaiser ACE score of 0 to 10 will be calculated as in the CDC-Kaiser ACE 
Study using the 11 questions that are in the BRFSS ACE module, 5 questions from the Childhood 
Trauma Questionnaire (CTQ) for an emotional neglect ACE, and 5 questions from the CTQ for a 
physical neglect ACE. This includes the parental divorce or separation question, but does not 
include the parental death question.
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4-
Modified CDC-Kaiser ACE score of 0 to 10 will be calculated. This includes one 
additional question about parental death which is incorporated into the parental separation or 
divorce category.
The BRFSS ACE and CTQ questionnaires are self-administered under the guidance of our 
study psychologist Dr. Dahlia Mukherjee. As is recommended, we preface these questionnaires 
by informing subjects beforehand that some of the questions may make them feel 
uncomfortable, and they are free to skip any of the questions they do not want to answer. 
If the study visit is conducted remotely, the subject will be e-mailed a link from REDCap to 
complete the self-administered questionnaires during the ( PSH Teams) live videoconferencing 
study visits.
The following questionnaires will be self-administered at the baseline study visit (and 
also at the 2-month and 6-month study visits), starting with the Toronto Mindfulness Scale after 
sitting quietly for 15 minutes:
The Toronto Mindfulness Scale (TMS) will assess mindfulness (Lau et al., 2006). Prior to 
completing the TMS questionnaire, subjects will be instructed to ‘‘sit quietly for the next 15 
minutes and pay attention to your breathing or anything else that might arise.’’ Afterwards, 
subjects will be asked to describe the degree to which each of the 13 items in the TMS described 
what they just experienced on a 5-point scale from 0 (not at all) to 4 (very much). The TMS 
measures an individual’s ability to generate mindfulness, a mode of curious, decentered 
awareness dependent on the development of a composite set of skills.
The Acupuncture Expectancy Scale will be modified to a Stress Reduction Expectancy 
Scale (SRES) and used to assess subjects’ expectations at baseline and at subsequent study visits 
(Mao et al., 2007; Mao et al., 2010; Bauml et al., 2014).
The 15-item Food Craving Questionnaire-Trait-Reduced (FCQ-TR) will be assessed as it 
has been shown to be responsive to a mindfulness-based intervention (Mason et al., 2017; 
Meule et al., 2014; Epel et al., 2014).
The 3-item Walking Enjoyment scale, an abbreviated version of the Physical Activity 
Enjoyment Scale (PACES), will be used to assess different aspects of walking enjoyment (e.g., ‘‘I 
enjoy doing brisk walking.’’) on a one- to five-point scale. Higher scores indicate greater 
enjoyment. The original PACES has adequate test-retest reliability (r =. 77) and good construct 
validity (Kendzierski & DeCarlo, 1991). The abbreviated version also has some validity though it 
is less than the original PACES. The abbreviated version is preferable for this study because it is 
shorter.
The 17-item Diabetes Distress Scale (DDS) will assess diabetes-related distress (Polonsky 
et al., 2005).
The Perceived Stress Scale-10 (PSS-10) will assess subjective stress (Cohen & Williamson, 
1988). The PSS-10 has been linked with adverse health outcomes and poor dietary and physical 
activity behaviors (Arnold et al., 2012; Barrington et al., 2012). Our pilot data shows PSS-10 
significantly improves with MBSR (Raja-Khan et al., 2017). 
The Short Form-12 (SF-12), a validated shorter version of the SF-36, will assess health 
related quality of life (Ware et al., 1996).
The Positive and Negative Affect Schedule (PANAS) will assess psychological affect 
(Watson et al., 1988).The Generalized Anxiety Disorder scale (GAD)-7 will also be self-
administered (Spitzer et al., 2006).
The PROMIS Short Form v1.0 Sleep Disturbance 8a will be self-administered. The 
PROMIS-Sleep Disturbance items assess self-reported perceptions of sleep quality, sleep depth, 
and restoration associated with sleep. This includes perceived difficulties and concerns with 
getting to sleep or staying asleep, as well as perceptions of the adequacy of, and satisfaction 
with, sleep. The PROMIS-Sleep Disturbance has demonstrated excellent validity as evidenced in 
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associations with disease activity, depression, female sex, smoking, and use of corticosteroids or 
narcotics (N=3173; inflammatory bowel disease) (Ananthakrishnan, 2013), ability to distinguish 
among those with and without sleep disorders (Buysse, 2010), and prediction (along with 
negative affect) of global ratings of improvement in back pain (Karp, 2014). The HealthMeasures 
Scoring Service, powered by Assessment CenterSM, will be used to score the PROMIS Short Form 
v1.0 Sleep Disturbance 8a. The HealthMeasures Scoring Service is a free, web-based application 
that scores an Excel file of raw participant responses and returns by email a file with calculated 
T-scores for all measures. Further details are available at: 
http://www.healthmeasures.net/index.php?option=com_content&view=category&layout=blog
&id=190&Itemid=1214
The Patient Health Questionnaire-9 (PHQ-9) will assess safety at each study visit 
(Kroenke et al., 2001; Van Steenbergen-Weijenburg et al., 2010). This will be self-administered 
at the study visits as described above in the screening visit. As in the screening visit, if a subject 
scores 1 or greater on the 9th item of PHQ-9, the research coordinator will interview the subject 
using the modified P4 Screener to assess suicide risk (Dube et al., 2010).
The Modified Coronavirus Impact Scale will be self-administered to assess how much 
the Coronavirus pandemic has impacted different aspects of subjects’ lives. This survey was 
modified from the Coronavirus Impact Scale created by Stoddard and Kaufman 
(https://www.nlm.nih.gov/dr2/Coronavirus_Impact_Scale.pdf).
Subjects will respond to additional questions in a Participant Questionnaire at the 
baseline visit (and subsequent study visits). This Participant Questionnaire will assess:
-   Adherence to Diabetes Medications by asking subjects to “Rate your ability to take all 
your diabetes medications as prescribed over the past month’’ (with six choices: Very 
poor, poor, fair, good, very good, and excellent) based on a previous study that 
determined that such a self-report measure most accurately assessed HIV medication 
adherence (Lu et al., 2008).
-   Follow-up Medical History by asking subjects if there have been any changes to their 
health since the last visit.
-   Number of sick days in the past 4 weeks
-   Questions about current employment status
-   A question about burnout
-   Questions about current use of tobacco and alcohol
-   Hair and nail care if they agreed to provide hair and nail samples
-   And other questions
The Counterfactual Measurement questionnaire will be self-administered at the 
baseline study visit (as well as at the 6-month study visit) to capture cross-contamination of 
behaviors throughout the study (e.g. active SME control subjects electing to participate in 
mindfulness activities). The Counterfactual Measurement questionnaire will ask subjects about 
the frequency and duration of engagement in mindfulness activities, other meditative activities, 
and other relevant activities over the past 6 months, both outside of the study and as a part of 
the study. Subjects’ responses at the subsequent study visits could reveal group assignment, 
thus the research coordinators will be blinded to the subjects’ responses to this instrument in 
REDCap. 
The Stress Experience Survey will be administered by the research coordinator at the 
baseline study visit (and also at the follow-up phone call after Class #4, the 2-month study visit, 
and the 6-month study visit). This includes questions about the 10 most common meditation-
related symptoms (items 1 to 10), as well as a question about other stress-related symptoms. 
This survey was adapted from Dr. Willoughby Britton’s MBP-Specific Adverse Effects Survey 
(Britton_Version9.18.19), which represents the 10 most common meditation-related symptoms 
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from the Varieties of Contemplative Experience Phenomenology Codebook (Lindahl et al., 2017), 
as replicated in an NIH-funded mindfulness-based intervention clinical trial (Britton, in prep). 
  
The Hypoglycemia Survey will be administered by the research coordinator at the 
baseline study visit (and also at the follow-up phone call after Class #4, the 2-month study visit 
and the 6-month study visit). The research coordinator will ask subjects about self-reports of 
Level 2 hypoglycemia (glucose < 54 mg/dL) and Level 3 hypoglycemia (hypoglycemia requiring 
the assistance of another person for treatment). Level 2 hypoglycemia will be recorded as an 
Adverse Event. Level 3 hypoglycemia will be recorded as a Serious Adverse Event (See DSMP).
Subjects will complete the Phone Call Time Preference questionnaire at the baseline 
study visit and at the 2-month study visit, as they did at screening, indicating their preferred 
windows of time to receive phone calls for visits and scheduling appointments. Subjects will be 
instructed that 3-hour windows of time are preferable (e.g. 6-9 PM on Wednesdays is better as 
it allows for more flexibility than 8-9AM, 1-2PM, and 5-6PM).
Data from subjects’ diabetes devices (glucometers, continuous glucose monitor (CGM), insulin 
pump and other smart insulin delivery devices) will be collected at each remote or in-person 
study visit: 
Description of the concept: Standards of medical care in diabetes include the use of 
glucometers by patients to self-monitor their blood glucose (SMBG) levels to achieve glycemic 
targets. In recent years, commercially-available continuous glucose monitors (CGMs), which 
measure interstitial glucose levels every few minutes for 24 hours a day, are increasingly being 
used by patients to monitor their glucose levels. In standard clinical practice, computer software 
are used to collect data from subjects’ diabetes devices (glucometers, CGMs, insulin pumps and 
other smart insulin delivery devices) in order to assess their glycemic control and determine 
changes in treatment. 
Description of the procedure: Subjects will be asked to bring their diabetes devices 
(glucometers, CGM, insulin pump and other smart insulin delivery devices) to each remote or in-
person study visit. At the screening visit, and at each subsequent study visit, the research 
coordinator will ensure that the date and time are correct on the subjects’ diabetes devices. The 
research coordinator will record the date and time that are on each device.  If the date or time 
on a device are not correct, the research coordinator will record the device date and time offset, 
and work with the subject to correct the date and time on the device. Correcting the date and 
time on the device does not correct the date and time of the data that has already been 
collected.
The research coordinator will obtain and record any available diabetes device data or 
reports that are provided by the subject or obtained from remote study Clarity/LibreView 
accounts, or clinic diabetes device accounts and medical records. This data will be manually 
recorded. The coordinator will collect reports of aggregated and raw data from these diabetes 
devices at the baseline, 2-month, and 6-month study visit time points. Aggregate reports will be 
collected for 14-days (which is the American Diabetes Association recommended standard for 
aggregating CGM data), 30-days, 60-days, and 90-days with an end date of the day before the 
study visit. All available reports will be collected e.g. Dashboard, Blood Glucose Trends-Hourly, 
Therapy Timeline, CGM Hourly, Logbook, etc. Strategies that may be used to collect this data 
include:

The subject will be asked to share data reports from their devices with the research 
team. 

The research coordinator will use computer software to collect the data from these 
devices at the study visits.
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
The research coordinator will use a secure cloud based diabetes-management system 
(e.g. Clarity, LibreView) to collect the subject’s data anonymously using their study ID 
number instead of their name or other identifying information. When applicable, 
subjects will be invited to upload or connect their diabetes devices to deidentified 
patient profiles in the study Clarity and LibreView accounts. 

The research coordinator will look through the data in a subject’s glucometer and 
record it e.g. In the case of a glucometer the research coordinator will record the 
following Summary screen data: % In-Range, Checks/Day, Highest glucose, Average 
glucose, and Lowest glucose in the past 14-days, 30-days, 60-days, and 90-days.

If the subject is a patient in the Endocrinology clinic, the coordinator will also have 
access to their diabetes device data in the Endocrinology clinic Glooko, Clarity and 
LibreView accounts.  

Diabetes device reports in the subject’s medical records.
Reports that are collected from devices-- will be saved in a secure location. Data will be 
abstracted from these reports. When available, data will be abstracted from the Ambulatory 
Glucose Profile (AGP) which is a standardized, single page report that includes glucose summary 
statistics. The AGP offers a report that is consistent regardless of device.
During the study, if a subject is not using a CGM, they will be advised to use their own 
glucometer and testing supplies to check their blood glucose at least four times per day, 
including:

Fasting (before breakfast or the first meal of the day) 

Before lunch 

Before dinner 

Before bed 

When having symptoms 
This is in-line with general recommendations for patients with uncontrolled diabetes, or patients 
on multiple daily injections of insulin or an insulin pump. If a subject is testing fewer than 4 
times a day, they will be advised to alternate their testing times e.g. check fasting and before 
lunch on some days, fasting and before evening meal on other days, and fasting and before bed 
on other days. 
 
The research coordinator will encourage subjects to bring their glucometers to each 
remote or in-person study visit even if they are not checking their blood sugars as prescribed. 
The research coordinator will encourage subjects to bring their CGM, insulin pump and other 
smart insulin delivery devices to each remote or in-person study visit even if they have not been 
using them every day. 
How/if devices need to be provided to subjects: Subjects will use their own glucometers, 
CGMs, and insulin pumps and other smart insulin delivery devices. At the screening, baseline 
and 2-month study visits, subjects who do not have a working glucometer but report using a 
glucometer before, will be offered a sample glucometer kit (if available), and advised to check 
with their insurance regarding coverage of additional glucometer testing supplies (e.g. test strips 
and lancets), and to see their PCP for prescriptions for additional glucometer testing supplies. 
The research coordinator will work with the subject to ensure that the correct date and time are 
set on the sample glucometer they are given. Subjects will be asked to bring their sample 
glucometer to their subsequent remote or in-person study visits so that data can be collected 
from them. Subjects paying out of pocket for glucometer testing supplies will be advised to 
consider Walmart’s ReliOn brand testing supplies which are more affordable. Subjects who have 
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never used a glucometer will be advised to see their PCP for a glucometer and referral to a 
Diabetes Educator.
Who will be managing this data: The research coordinator will be managing this data. 
When will this data be collected throughout the trial: We will collect this data from 
subjects’ diabetes devices (glucometers, CGMs, insulin pumps and other smart insulin delivery 
devices) at their remote or in-person baseline, 2-month, and 6-month study visits. 
What important pieces of data are being collected from this procedure throughout the 
trial: 
Glucometer Data to be collected include:
- Glucometer download start and end dates
- Average blood glucose level from glucometer (mg/dL) overall and during 
specific times of the day (Morning, Afternoon, Evening, and Night time 
windows)
- Standard deviation of all blood glucose readings from glucometer (mg/dL)
- Number of blood glucose readings per day on average (Readings/Day)
- Total number of blood glucose readings (# Readings) 
- Percent of blood glucose readings Above target (frequency of hyperglycemia)
- Percent of blood glucose readings In Range
- Percent of blood glucose readings Below target (frequency of hypoglycemia)
- Lower limit of overall target from glucometer (mg/dL)
- Upper limit of overall target from glucometer (mg/dL)
- Lowest blood glucose reading (mg/dL) 
- Highest blood glucose reading (mg/dL)
- Device information, e.g.
Glucometer #1: Name of Device, Device time offset (hh:mm), and Last sync date 
Glucometer #2 Name of Device, Device time offset (hh:mm), and Last sync date
Additionally, from the above glucometer data, we will be able to determine the Coefficient of 
Variation (CV), which is a measure of glucose variability calculated as the standard deviation 
divided by the mean glucose. The CV has been proposed as the preferred measure of glucose 
variability (Suh & Kim, 2015; DeVries, 2013; Rodbard, 2011). Glucose variability is a challenge for 
many patients with diabetes as it increases one’s risk for hypoglycemia and has been linked with 
increased cardiovascular risk in some studies (Jun et. al., 2015).
CGM Data to be collected include:
- Name and Model of CGM device
- CGM download start and end dates
- Number of days included in the download 
- Average glucose level overall from CGM (mg/dL) 
- Average glucose level every hour from CGM (e.g. midnight to 1AM, 1AM to 
2AM, 2AM to 3AM, etc.) 
- Percent of glucose readings Very Low (< 54 mg/dL) as the frequency of severe 
hypoglycemia from CGM
- Percent of glucose readings Low (< 70 mg/dL) or below target as the frequency 
of all hypoglycemia from CGM
- Percent of glucose readings In Target Range (70 – 180 mg/dL) from CGM 
- Percent of glucose readings High (> 180 mg/dL) or above target as the 
frequency of all hyperglycemia from CGM
- Percent of glucose readings Very High (> 250 mg/dL) as the frequency of 
severe hyperglycemia from CGM
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- Coefficient of Variation (%) as a measure of glucose variability from CGM 
- Standard deviation of glucose (mg/dL) as another measure of glucose 
variability from CGM
- Lower limit of overall target from CGM (mg/dL)
- Upper limit of overall target from CGM (mg/dL)
- Percent of Time CGM Active for Dexcom CGM users
Collected measures will include the standardized CGM metrics for clinical care recommended by 
the American Diabetes Association and the International Consensus on Time in Range for CGM 
(American Diabetes Association 2019b; Battelino et al., 2019): 
1- Number of days CGM worn (recommend 14 days) 
2- Percentage of time CGM is active (recommend 70% of data from 14 days)
3- Mean glucose
4- Glucose management indicator (GMI)
5- Glycemic variability (% Coefficient of variation) target ≤ 36%
6- Time above range (TAR): % of readings and time in hyperglycemic range, i.e., >250 mg/dL 
(level 2), 181-250 mg/dL (level 1)
7- Time in range (TIR) % of readings and time in target range, i.e., 70-180 mg/dL
8- Time below range (TBR) % of readings and time in hypoglycemic ranges, i.e., <54 mg/dL (level 
2), 54-69 mg/dL (level 1)
Insulin pump data to be collected include: 
- Name of insulin pump
- Name of insulin used in insulin pump
- Aggregate Number of Days
- Average Daily Carbs (grams/day)
- Standard deviation of daily carbs (grams/day)
- Carbs/Bolus Insulin (grams/Units)
- Average Total Daily Dose of Insulin (units of insulin per day)
- Standard deviation of number of units of insulin per day
- Average Daily Basal Insulin (units/day)
- Percent Basal Insulin
- Average Daily Bolus Insulin (units/day)
- Percent Bolus Insulin
- Average Number of boluses per day
For those subjects with a Medtronic Insulin pump Hypoglycemic and Hyperglycemic Patterns will 
also be collected
Accelerometer data will be collected using the Actigraph wGT3X-BT activity monitor to 
objectively measure physical activity (optional protocol procedures): 
Description of the optional Actigraph wGT3X-BT device and how it should be worn and 
for how often: The Actigraph wGT3X-BT activity monitor is a small, unobtrusive tri-axial 
accelerometer (an activity monitor that is similar in size and function to a pedometer, but more 
accurate than a pedometer). Compared to four other commonly used accelerometers, the 
Actigraph was found to have the least variability and the highest overall reliability with G values 
above .60 and ICC values above .80 (Welk et al., 2004; Sasaki et al., 2011).  
If a subject opts in to wearing an Actigraph and collecting the accelerometer data, they 
will be instructed to wear the Actigraph for at least 12 hours a day over at least 7 days around 
each of 3 study visit time points (baseline, 2-month, and 6-month). The time windows for 
capturing the optional Actigraph data are +/- 2 weeks of the baseline and 2-month study visits, 
and in the 4 weeks before the final 6 month study visit. Subjects will be provided with a 
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waistband/belt and instructed to wear the Actigraph on the waistband/belt over their hipbone, 
in line with their knee. They will also be asked to keep a written daily log of their Actigraph wear 
time, including when they put on/took off the Actigraph to enable additional confirmation of the 
Actigraph activity data. Subjects will be instructed to put the Actigraph on first thing in the 
morning when they wake up and record the time on their log, and to take it off at night just 
before getting into bed and record the time on their log. Subjects will be instructed not to wear 
the Actigraph when sleeping, showering or swimming, and to note on the log if they briefly 
removed the Actigraph. 
The research coordinator will ensure that subjects understand how to accurately wear 
the Actigraph, and provide them with written instructions on how to wear the Actigraph. 
How the optional Actigraph devices will be provided to the subjects: The research 
coordinator will either (1) Provide the Actigraph to the subject at their study visit along with 
instructions on how to wear the device and a postage paid envelope to mail the device and 
Actigraph Wear Time Log back after they have worn it for 7 days, or (2) Mail the Actigraph to the 
subject with instructions on how to wear the device. The preferred method for in person visits 
will be to provide the Actigraph to the subject at their baseline and 2-month visit, and mail the 
Actigraph to the subject before their final 6-month study visit. When subjects will be given the 
Actigraph at an in-person study visit, the subject’s weight from the in-person visit will be used to 
initialize the Actigraph. When subjects will be mailed the Actigraph, their weight from their 
medical records if within the study visit time window will be used, and if that is not available 
then their weight from their last study visit will be used, and if that is not available then a self-
reported weight will be used. If the baseline and 2-month visits are conducted remotely, the 
Actigraphs will be mailed to the subject. For remote and in-person study visits, the Actigraph will 
be set to start recording at midnight and subjects will be instructed to start wearing the 
Actigraph the morning after they receive it.  
The research coordinator will call the subject if the Actigraph was not returned within 14 
days after they were scheduled to start wearing it.  
The research coordinator will follow the recommended steps to test, initialize and fully 
charge the Actigraph prior to each use. Each new Actigraph device will be worn and tested by 
the research team, and the test data will be reviewed briefly by the research team. Actigraph 
devices will be sanitized and waistbands laundered in between use. Actigraphs will be labeled 
with who to call and where to return the device if lost and found.
Who will be managing and aggregating this data: The research coordinators will initialize 
the devices, and upload the (optional) collected Actigraph data into the ActiLife software 
platform. Biometric data (height, weight, date of birth, dominant side, etc.) is entered at the 
time the devices are initialized and prepared for distribution for data capture. The most current 
updated weight measurement available to the research coordinator will be used to initialize the 
device (whether that be measured at an in-person study visit, extracted from the medical 
records, or self-reported by the participant, when necessary). This information is important to 
obtain accurate metabolic equivalents (METs) calculations in the software algorithms/formulas 
(because a change of a few kilograms will have an effect on the energy expenditure and METs 
calculations). When applicable/necessary, it is possible that the biometric data may also be 
entered/updated at the time of scoring at the end of the study.  The research coordinators will 
work with the data manager/statistician to reconcile any data entry or quality issues. Refer to 
the Actigraph Device Data Monitoring SOP for more detailed information and procedures. As the 
processing and wear-time validation of accelerometer data is a developing and evolving field, 
the wear-time validation algorithm and criteria will be decided for analysis at the end of the 
study, when more current literature can be reviewed. If possible, ideally the wear period will 
meet either the initial Sallis validation criteria of at least 5 valid days containing at least 10 valid 
hours per day, or the alternate Sallis validation criteria of at least 66 valid hours (Cain & 
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Geremia, 2012). At the end of the study, once the wear-time validation algorithm and 
processing criteria are decided upon after review of more current literature at that time, the 
Actigraph data will then be processed and scored for analysis, likely using Freedson VM3 2011 
for Energy Expenditure Scoring and Cut Points/MVPA Scoring (Sasaki et al., 2011), and Freedson 
1998 for METs (unless Freedson VM3 2011 or updated algorithms become available options 
later at the time of scoring and analysis) (Freedson et al., 1998).  Actigraph data will be reviewed 
regularly by the data manager/statistician. Kalen Kearcher, MS, ACSM EP-C, an exercise 
physiologist experienced in using the Actigraph, will be briefly available for consultation with the 
research team regarding questions in the use of the Actigraph wGT3X-BT and the ActiLife 
software that will be used to score the data. The research team will read the ActiLife 6 User’s 
Manual, the User Guide for the ActiGraph wGT3X-BT + ActiLife, and Sallis’s Accelerometer Data 
Collection and Scoring Manual For Adult & Senior Studies (Cain & Geremia, 2012). 
How often will this data be collected throughout the trial: This optional data will be 
collected for 7 days around each of 3 study visit time points (baseline, 2-month and 6-month).
What important pieces of data are being collected from the Actigraph wGT3X-BT devices 
throughout the trial: 
The optional Actigraph will be worn for 7 days and data will be stored as 10 second 
epochs (and possibly later converted to 60-second epochs). This data will be used to determine 
average daily: 
-
Step count data
-
Sedentary – Length of time in minutes in Sedentary activity [<100 counts per minute (60-s 
epoch)]
-
Light - Length of time in minutes in Light physical activity [100-1951 counts per minute (60-s 
epoch)]
-
Moderate - Length of time in minutes in Moderate physical activity [1952-5724 counts per 
minute (60-s epoch)] 
-
Vigorous - Length of time in minutes in Vigorous physical activity [5725-9498 counts per 
minute (60-s epoch)]
-
Very Vigorous - Length of time in minutes in Very Vigorous physical activity [≥9499 counts 
per minute (60-s epoch)]
-
Moderate to Vigorous Physical Activity (MVPA) – Length of time in minutes in MVPA [3 
metabolic equivalents (METs) or greater] (≥ 1952 counts per minute) using established 
activity count “cut-points” (Freedson & Miller, 2000). Total minutes of MVPA on valid days 
will be divided by the number of valid days to obtain the average daily minutes of MVPA.
-
Other measures
Dr. Liza Rovniak, an NIH-funded exercise scientist, will provide her expertise and 
consultation in the assessment of these data. 
24-hour Dietary Recall Surveys (optional protocol procedures):
Dietary intake data for 24-hour recalls (optional) will be collected and analyzed using the 
Automated Self-Administered 24-hour (ASA24) Dietary Assessment Tool, version 2020 and 
version 2022, developed by the National Cancer Institute, Bethesda, MD 
(https://epi.grants.cancer.gov/asa24). Optional modules that will be included in the ASA24 are: 
Location, Food Source, TV/Computer, and Nutrition Report Viewing. The amount of time 
provided to complete the ASA24 recall will be set to 24 hours so that it has to be completed by 
midnight of the prompted reporting day (and so that the intake day is always referenced as 
‘yesterday’ when participants are prompted to complete the 24-Hr Recall). This means subjects 
will get an email invitation to complete the ASA24 recall in the morning and have until midnight 
to complete it, recording data about the foods they have eaten throughout the entire (24 hour) 
previous calendar day. The research coordinator will provide subjects with information about 
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the ASA24 self-administered dietary assessment tool, handout titled ASA24 /Quick Start Guide 
24 hr recall, and the following link to the ASA24 demo as part of their introduction/training 
https://asa24.nci.nih.gov/demo/. The research coordinator will send subjects 2 unannounced 
emails inviting them to complete 1 weekend and 1 weekday diet recall (optional) on the ASA24 
website during the following time windows: within 2 weeks before Class #1, 2 weeks after Class 
#8, and 2 weeks before Booster #4 (Miller et al., 2009). These emails will include the link to the 
ASA24 website, and the username and password the participant will need to enter to complete 
a recall. Participants will need to be connected to the internet to complete a recall. The research 
coordinator will visit the ASA24 Researcher Website to view participants’ data, and monitor the 
number of completed intakes per participant. If a subject does not complete a diet recall, the 
research coordinator will contact the subject and remind them to check their email every day, 
and then send another unannounced email inviting the subject to complete the diet recall.  
All food intake (24-hour recall) data, data about the foods they have eaten on the 
previous day, will be collected via the ASA24 self-administered dietary recall. The types of 
questions that are asked depend on the foods they have eaten.  See attached sample ASA24 
overview 2020, and ASA24 - 2020 researcher instructions.  
Data Storage, Security and Transmission: Researchers using the ASA24 system do not provide 
the NCI, Westat, or the ASA24 system with any identifying data for participants of their studies. 
Rather, researchers specify a unique numeric identifier for each respondent and download 
system-generated usernames and encrypted passwords that they provide to respondents so 
that they may access the application. 
The ASA24 system also does not collect any identifying data directly from respondents. 
However, IP address information is accessed for the purpose of routing information between 
the server and the respondent's computer—often the IP address is that of the user's Internet 
Service Provider (ISP). IP addresses are not stored or tracked by the ASA24 system. However, 
logs of connections are kept in the hosting environment for audit trail purposes. This 
information is not mined in any way but would be available if there were a legal obligation to 
release it.
Response data are secured at the hosting site using industry standard security controls, 
including firewalls and encryption. All data entered into the ASA24 system at the respondent’s 
computer is encrypted by the internet browser (e.g., Internet Explorer, Firefox) before they are 
transmitted to our servers using Secure Socket Layer (SSL) Technology. SSL allows for the 
authentication of the sending and receiving computers. 
Only a particular study’s investigator(s) and the ASA24 operations team can access response 
data. Access is gained through usernames and strong passwords. Data are maintained in the 
ASA24 system for a period of at least one year (unless the Researcher requests an earlier date 
for data purging). Researchers will be notified before their data are removed from the system.
Who will be analyzing this data: This data will be analyzed by the study biostatistician.
When will this data be collected throughout the trial: 24-hour dietary recall data 
(optional) will be collected on 1 weekend and 1 weekday within 2 weeks before Class #1, 2 
weeks after Class #8, and 2 weeks before Booster #4. 
How often will this data be collected throughout the trial: Two 24-hour dietary recalls 
(optional) will be collected on each subject around each of 3 study visit time points (baseline, 2-
months, and 6-months) so each subject will have a maximum of six 24-hour dietary recalls.
What important pieces of data are being collected from this procedure throughout the 
trial:
-total energy intake
-carbohydrate intake
-fat intake
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-protein intake
-Healthy Eating Index
There are many more variables that are generated automatically from the intake data so 
final data sets will contain more variables. Additional variables of interest include glycemic 
index, glycemic load, fiber, added sugars, fruits, vegetables etc. 
These variables will be collected as the total for each 24-hour recall period.
Experience Sampling: Daily Stress & Cravings and Daily Diary Surveys      
We will use experience sampling to collect daily repeated measures of participant stress levels, food 
cravings, and use of stress-management strategies in naturalistic contexts. Experience sampling is 
designed to overcome the limitations of retrospective self-report and recall bias by collecting brief, but 
frequent repeated reports of participant emotions, experience, and behavior. Experience sampling 
surveys will be administered on a daily basis to all subjects between the baseline study visit and the final 
6-month study visit (or the time they are deemed lost-to-follow up or are withdrawn from the study). 
These surveys were initially administered four times a day via Qualtrics for the first few study cohorts. 
They are now being administered once a day via REDCap. 
REDCap Daily Stress & Cravings Survey and Daily Diary Survey. All participants eligible to be 
randomized after completion of their Baseline visit will receive one email invitation per day asking them 
to complete the Daily Stress & Cravings Survey questions. There will be 3-4 Daily Stress & Cravings 
Survey questions which will take approximately 15-20 seconds to complete. Each survey will inquire 
about participant experiences “between 8 PM last night and 8 PM tonight.” 
Between Class #1 (or #2) and the final 6-month study visit (or the time they are deemed lost-to-
follow up or are withdrawn from the study), the daily email invitation participants receive will ask them 
to complete both the Daily Stress & Cravings Survey questions and the Daily Diary Survey questions. The 
Daily Diary Survey questions will ask participants about the stress management activities they engaged 
in “between 8 PM last night and 8 PM tonight”, and the amount of time spent engaged in each activity. 
Participants will only be asked about activities relevant to the specific condition the participant is 
assigned to. Participants assigned to the treatment (MBSR) condition will complete 10 questions, which 
takes between 10-50 seconds to complete. Participants assigned to the comparison (SME) condition will 
complete 2 questions, which takes between 5-10 seconds to complete.  
Data Security
Unblinded research team members e.g. the SME instructors will have access to the 
randomization list in REDCap so that they will be able to check and make sure that subjects are 
completing the correct Daily Diary Survey questions that correspond to their group assignment, 
MBSR or SME.
During the study, subjects will be compensated an additional $15 if they respond to at 
least 70% of the Experience Sampling Surveys by their 2-month study visit. 
Between the baseline study visit and Class #8, unblinded research team members e.g. 
the SME instructors will periodically review reports of subjects’ Experience Sampling Survey 
response rates, and if a subject’s response rate for the Experience Sampling Surveys (Stress and 
Cravings or Daily Diary) ever falls below 70% in a week, the SME instructor or other unblinded 
research coordinator will call the subject to troubleshoot. 
Between the 2-month study visit and the 6-month study visit, the SME instructor or 
other unblinded research coordinator will be making monthly phone calls to the subjects to 
remind them of their booster sessions and encourage retention in the study. During these 
monthly phone calls, the research coordinator will encourage subjects to continue to respond to 
as many of the Experience Sampling Surveys as they are able to as their responses are very 
important in helping the research team better understand how day-to-day stresses affect 
people living with diabetes.
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Who will be managing this data: Unblinded research team members e.g. the SME 
instructors will be managing this data. Due to the nature of this data, specifically because the 
MBSR and SME groups have different Daily Diary of home practice questions and responses, 
which would reveal group assignments, the research team members managing this data e.g. the 
SME instructors will not be blinded. Blinded study team members will not have access to the 
Experience Sampling Surveys in REDCap.
Who will be analyzing this data: The study biostatistician will analyze this data with input 
from Dr. Raja-Khan. However, any data that identifies the group assignments of the subjects 
(e.g. Daily Diary survey questions and responses about their home practice, instructors’ names, 
etc.) cannot be analyzed by the study biostatistician or any of the blinded study team members 
until the study is unblinded.
At the end of the baseline visit, if a subject is deemed fully eligible for inclusion into the study, 
the research coordinator will:

Inform the subject that they will receive a Randomization phone call during the week 
before Orientation

Schedule the subject for the following:
o
Follow-up phone call within 2 weeks after Class #4
o
2-month study visit
o
6-month study visit

Give the subject written instructions and reminders for the following:
o
Randomization phone call in the week before Orientation
o
Follow-up phone call within 2 weeks after Class #4
o
2-month study visit

Give the subject a Wallet card reminding them not to say anything that would reveal 
their group assignment when speaking to blinded study staff on the phone or at the 
study visits. The card will instruct the subject to call the research coordinator if they 
have any questions. The contact information for the research coordinator will be 
included on the card. 
Data Collection Procedures: 
Data will be collected in a thorough and systematic manner. Only study personnel blinded to 
group assignment will collect outcomes. We have selected measures that are quick to 
administer and complete to minimize burden. All data will be managed via a single platform, 
REDCap, a HIPAA compliant platform designed for research studies.
Data Management: 
All data for this project will be promptly entered into a computerized database. Subject 
identifications will be kept separate in locked files and will be destroyed when no longer needed 
for the project. To minimize errors, measures will be verified prior to data entry and computer 
verification will be employed during data entry. Data files will be backed up and archived 
regularly.
7.2.4
Randomization and Study Intervention
Randomization is a critical feature of a clinical trial because it prevents treatment-selection 
biases. Subjects will be randomized after obtaining their baseline measurements and within 1 
week before the start of the study intervention (Orientation). It is anticipated that the amount 
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of time between randomization and the start of the study intervention (Orientation) will be no 
more than 1 week. There will be rolling enrollment. We will run a new cohort of MBSR and SME 
control classes approximately every 3 months. Subjects will only be randomized to a cohort if 
they indicate they are available for the intervention classes for that cohort.
Two hundred ninety (290) adults with uncontrolled diabetes will be randomized with 
equal allocation to one of two study groups for 6 months: (1) MBSR (n=145), or (2) SME control 
(n=145). Subjects will then undergo study visits again at 2 months (after Class #8/after the 
standard 8-week MBSR or SME program) and at 6 months (after Booster session #4/end of 
study), where the baseline procedures and measures will be repeated.  
During the study, all subjects will continue to receive usual care from their physicians 
and will be advised not to change or discontinue any of their medications during the study 
unless directed to do so by their physician. As these subjects have uncontrolled diabetes, it is 
expected that they will be on medical treatment as prescribed by their physician, and they will 
be advised to follow-up with their physician every 3 months to ensure they are on optimal 
medical treatment. During the study, all subjects will be encouraged to continue their routine 
activities and they will be asked not to take part in any other formal stress reduction programs.
Randomization to MBSR or SME control will be performed within REDCap using a 
pseudo-random number generator via the PLAN procedure within SAS software, version 9.4 
(SAS Institute Inc., Cary, NC). Personnel in the Department of Public Health Sciences will use the 
PLAN procedure within SAS software to generate a randomization list using variable-size, 
random permuted blocks to ensure that the number of subjects in each treatment arm is 
balanced after each set of B randomized subjects, where B is the block size. Using a 1:1 
allocation ratio, there will be 145 subjects assigned to each study group. Randomization will be 
stratified by insulin vs. non-insulin treated subjects to make sure the two groups are balanced as 
this is a potential confounder. Personnel in the Department of Public Health Sciences will choose 
the block sizes without revealing it to any of the blinded investigators or study personnel who 
will be collecting and reviewing outcomes data. Study group data will be presented in a blinded 
fashion within DSMB reports.
Randomization to MBSR or SME control will be performed by the SME instructors in 
REDCap during the Randomization phone call as described below. Study group assignments will 
not be communicated to research personnel who will be collecting and reviewing outcomes 
data. The SME instructors will communicate the study group assignments to the subjects and 
the MBSR instructors. The subjects and instructors will be asked to keep the assignments 
concealed from the blinded investigators and study personnel. The PI, research coordinators 
and all study personnel involved in the collection and review of outcomes data will be blinded.
Overview of study instructors and roles
There are two types of instructors in the study: the MBSR instructors and the SME instructors. The MBSR instructors 
and SME instructors will have access to participants’ Orientation Reports in REDCap. The MBSR instructors are 
expected to directly communicate to the SME instructor about participant attendance at the MBSR sessions. The 
SME instructors are expected to record participant attendance at the MBSR and SME sessions.
Randomization Phone Call (by the SME instructor within 1-week before Orientation): 
At the end of the baseline visit, if a subject is deemed fully eligible for inclusion into the study, the research 
coordinator will inform the SME instructor, or other designated unblinded study team member, that the subject can 
be randomized during the week before Orientation. The SME instructor will disseminate the allocated randomized 
intervention to the subjects in their cohort, as the SME instructors are not blinded and they are not involved in the 
collection or analysis of study outcomes. During the Randomization phone call, the SME instructor will complete the 
following procedures to randomly assign the subjects in their cohort to one of two study groups (MBSR or SME) in 
REDCap:
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
The SME instructor will call the subject in the week before the Orientation session. 
o
If the SME instructor is unable to reach the subject for randomization, the SME instructor will email 
the subject to follow-up (See SME Instructor Email Template Randomization No Contact Made).

The SME instructor will verify that the subject is still available for the study sessions. Subjects will be 
informed that they must attend the Orientation session to continue in the study. If they miss the 
Orientation session, and are unable to make up the Orientation before Class #2, they will not be able to 
continue in the study. If a subject thinks they will miss the Orientation, or if they think they will miss more 
than 2 classes during the first 8 weeks (including Class #1 to 8 and the Retreat), they will be encouraged to 
wait for another wave/cohort when they are able to make the time commitment. The SME instructor will 
not randomize any subjects who cannot commit, with reasonable certainty, to completing an Orientation 
session before Class #2, and at least 7 out of 9 classes during the first 8 weeks (including Class #1 to 8 and 
the Retreat).

Upon confirming the subject’s commitment to attendance and interest in participation, the SME instructor 
will select the randomization button in REDCap while they are still on the phone with the subject. Once the 
button is selected, the live feedback from REDCap will display the assigned group. In the same phone call 
(using a Randomization Script), the SME instructor will immediately inform the subject of the details of their 
group assignment, give them a brief pre-orientation of the program, and provide the subject with:
o
Welcome information 
o
Their instructors’ names (Update at each wave)
o
Their instructors’ contact information (Update at each wave)
o
The Zoom Information for their class, and guidance on how to use Zoom. All MBSR and SME 
sessions will be conducted via Penn State University (PSU) Zoom.
o
The times and dates of their 14 study sessions (Update at each wave):
Orientation session that will last 1 and a half to 2 hours (1 session). 
Class #1 to 8: These sessions are once a week during the first 8 weeks, starting 
approximately 1 week after Orientation. The duration for each of these sessions will be 2 and a 
half to 3 hours (8 sessions).
Retreat: A single longer MBSR or SME session that will last 7 hours (1 session)
Booster sessions #1 to 4: These are 45-minute long MBSR or SME booster sessions every 
month in Months 3, 4, 5 and 6 (4 sessions). 
Attendance will be recorded at each session. Subjects will be instructed to let their 
instructor know if they need to be excused from a session. It is possible that for some 
unforeseen reason a subject misses a session. If this happens, the subject may not be able to 
make the session up, but they will be encouraged to continue to follow along with the home 
practice and do their best to attend all the remaining sessions that they are assigned to.
o
After speaking with the subject and providing them with an overview of their group assignment via 
phone, the SME instructor will email the subject the details of their group assignment (See SME 
Instructor Email Template Randomized to MBSR and SME Instructor Email Template Randomized to 
SME).
The SME instructor will inform the subjects that after Class #8, they will start receiving emails inviting them 
to participate in additional Retreat sessions and monthly booster sessions (See SME Instructor Email 
Template After Class #8 MBSR Booster Reminder and SME Instructor Email Template After Class #8 SME 
Booster Reminder). The monthly booster sessions in months 3 to 6 are required sessions for the study. The 
remaining booster sessions, and any additional Retreat sessions after Class #8, are optional sessions that 
subjects may choose to participate in if they wish. Attendance will be recorded at these additional sessions, 
however subjects will not receive any financial compensation for participating in the optional sessions. 
Subjects will be advised to contact their instructor if they have any questions or concerns about their 
sessions or home practice. 
The SME instructor will remind the subject that the above information should ONLY be discussed with their 
course instructor (unblinded staff members), and should not be discussed with the blinded research 
coordinators or any other study staff that they communicate with at study visits or via phone calls who are 
blinded to group assignments.   
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The SME instructor will provide the subject with their own contact information so if the subject has any 
questions about the above they can contact the SME instructor. The SME instructor will need to agree to be 
easily accessible to any and all subjects that contact them with questions pertaining to their study group.
The SME instructor will answer any questions subjects may have during the Randomization phone call. 
The name of the SME instructor will be captured within REDCap each time they randomize a subject as 
the SME instructor randomizing subjects is subject to change with each cohort/wave.  
Additional procedures the SME instructor will complete during the week before Orientation: 

Before 8 AM on the day of the Orientation, the SME instructor will send (via Secure File Transfer - SFT) the list of 
randomized MBSR subjects with their contact information (Name, Email Address, Phone Number) to the MBSR 
instructors. 
Other study procedures the SME instructor will complete:
Once an SME instructor randomizes a subject to MBSR or SME, that SME instructor will be responsible for 
following that subject throughout the time that the subject is in the study, and completing any study procedures 
that cannot be completed by the blinded research coordinators, including:

By Class #1, record the number of subjects in their cohort randomized to each group (and any other needed 
information) in the Unblinded Classes sheet in the Excel Study Tracking Spreadsheet in Google Drive. This 
information will be used by unblinded research team members e.g. the SME instructors, to check that the 
correct number of subjects started up the MBSR and SME Daily Diary surveys after Class #1. Blinded study team 
members cannot be aware of the number randomized to each group in a cohort since this could reveal group 
assignments. 

Coordinate the documentation of attendance at the MBSR or SME sessions for each subject in their cohort (See 
the section below entitled “Attendance”)

To encourage subject retention in the study, and to parallel what is commonly done in MBSR, after Class #8, the 
instructors will invite the subjects to participate in additional MBSR or SME Retreat sessions and monthly 
booster sessions (See SME Instructor Email Template After Class #8 MBSR Booster Reminder and SME Instructor 
Email Template After Class #8 SME Booster Reminder). The monthly booster sessions in months 3 to 6 are 
required sessions for the study. The remaining booster sessions, and any additional Retreat sessions after Class 
#8, are optional. Attendance will be recorded at these additional sessions, however subjects will not receive any 
financial compensation for participating in the optional sessions. 

The SME instructor will serve as the point-of-contact for any and all communications between the MBSR/SME 
instructors and the blinded research team about subjects in a manner that does not reveal a subject’s group 
assignment (See the section below entitled “Blinding”).

A subject’s SME instructor will be the one main point person that the subject can contact with any questions 
about the study. This will be very important in building rapport with the subject and encouraging retention in 
the study. 

Any other study procedures that cannot be completed by the blinded research coordinators.
 Attendance:
The SME instructor for each cohort/wave will coordinate the documentation of attendance for each MBSR and 
SME subject in their cohorts throughout the 6 months that the subjects are in the study. Subjects’ attendance 
will be documented for the Orientation session, Class #1 to 8, the Retreat session, Booster sessions #1 to 4, and 
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any additional optional study booster sessions and retreat sessions that subjects participate in while they are in 
the study. Attendance will be recorded by the MBSR or SME instructor at the beginning of each Zoom session. 
For the purposes of this study, ‘attendance’ is defined as attending the class in full, entering the class late, 
and/or leaving the class early (e.g. partial attendance will count as full attendance). 
Within 24 hours of each session, the SME instructors will record the attendance for each of the MBSR and SME 
subjects, in the Blinded Attendance Log in REDCap. Blinded study team members will be able to review the 
Blinded Attendance Log as it will not contain any information that would reveal group assignments. 
Procedures for when a subject misses a session: The protocol for contacting subjects who miss a session will be 
similar for both MBSR and SME groups. The following procedures will be completed when a subject misses an 
MBSR or SME session that they are assigned to: 

If a subject misses the Orientation session after being randomized, the subject’s instructor (either MBSR 
or SME) will contact the subject and offer them an individual Orientation session. If a subject does not 
complete Orientation after being randomized to MBSR or SME prior to Class #2, the SME instructor will 
notify the research coordinator and the subject will be withdrawn from the study.

If a participant misses a Class #1 to 8 session, Retreat session or booster session, the subject’s instructor 
(either MBSR or SME) will complete the following procedures: 
o
Send a follow-up email if someone misses a class and let them know we missed them. 
o
Encourage them to continue to follow along with the home practice and do their best to attend 
all the remaining sessions that they are assigned to. 
o
Offer to be available by email, phone call, or schedule a time to meet usually before or after the 
next class, if they wish to have a private discussion. 
o
The SME instructor will ask the MBSR instructor to let them know if they receive any 
communication from a study participant regarding a missed session.

After 48 hours of the missed session, if a study participant in MBSR or SME, has not communicated with 
the instructors regarding a missed session, the SME instructor will call the participant. 

Each MBSR and SME instructor will keep a Participant Contact Log, where they record each time they 
attempt to contact a study participant in MBSR or SME (via phone or email) for missing a session. Each 
instructor will maintain their Participant Contact Log securely themselves, and they will hand this log in 
to the research team at the end of the study. If the research team needs any information on this log 
before then, the MBSR instructor will securely share their log with the SME instructor who will securely 
share the needed information with the research team in a blinded manner. This log will include the 
following for each contact attempt:
o
Date and time of each contact attempt
o
Whether the contact attempt was via phone or email
o
Whether or not the subject responded (confirming successful contact), and if the subject 
responded:
Date of subject response
Whether the subject’s response was via phone or email
Any reasons the subject provided for missing the session, and 
Whether the subject confirmed that they will or will not be attending the subsequent 
sessions. 

If a subject has 2 consecutive unexcused absences from MBSR or SME, the SME instructor or other 
unblinded research coordinator will contact the subject, and encourage the subject to continue to follow 
along with the home practice and do their best to attend the sessions. Subjects will be advised to 
contact their instructor if they have any questions or concerns about their sessions or home practice. 
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Blinding: 
The PI, research coordinators and all other research team members involved in the collection or 
review of outcomes data will be blinded. The random assignment of subjects to MBSR or SME 
will not be communicated to any research team member who will be collecting or reviewing 
outcomes data.  The subjects, SME instructors, MBSR instructors, data manager, video coders, 
Dr. McCown will be asked to keep the study group assignments concealed from the blinded 
investigators and study personnel. 
The SME instructors, MBSR instructors, and other unblinded research team members will be 
asked not to reveal the number of study subjects in an MBSR course, or in an SME course, to the 
research coordinators and other blinded research team members. 
The research coordinators and other blinded research team members will be:

Blinded to the number of subjects randomized to MBSR in a cohort/wave

Blinded to the number of subjects randomized to SME in a cohort/wave
The research coordinators and other blinded research team members will be:

Aware of the total number of subjects randomized in a cohort/wave
Subjects will be asked to keep their study group assignment concealed from the blinded study 
personnel, including the research coordinators and other study personnel that they meet during 
the study visits. At the beginning of any phone call, study visit, or other contact with a subject, 
blinded research team members will remind subjects not to say anything that would reveal their 
group assignment e.g. instructors’ names, specifics about their classes or Daily Diary survey  
questions, the PSU Zoom link for their classes, etc. 
The research coordinators and other blinded research team members will not have access to the 
Experience Sampling Surveys in REDCap, which will be managed by unblinded research team 
members e.g. the SME instructors. Additionally, the PSU Zoom links for the classes will only be 
available to Dr. McCown and the instructors as these individuals will not be blinded.
Procedures in the MBSR group will parallel procedures in the SME group to maintain blinding. As 
an example, since subjects in the MBSR group are not allowed to continue with MBSR if they 
miss Orientation, the same will apply for subjects in the SME group. Additionally, if a session for 
one group needs to be canceled for any reason, the concurrent session for the other group will 
also be canceled. 
The SME instructors will serve as the point-of-contact for any and all communications between 
the MBSR/SME instructors and the blinded research team about subjects, in a manner that does 
not reveal a subject’s group assignment. The MBSR instructors and SME instructors will be given 
each other’s contact information. Any subject-specific information, including any potential 
adverse events that an instructor becomes aware of in an MBSR subject, or in an SME subject, 
(e.g. requiring a change in MBSR or SME practice recommendations), will be communicated to 
the blinded research coordinator through the SME instructors, in a manner that does not reveal 
the subject’s group assignment. The MBSR instructors will avoid directly communicating with 
the blinded research coordinator and other blinded research team members about specific 
subjects. The MBSR instructors will directly communicate information about MBSR subjects to 
the SME instructors. The SME instructors will communicate information about MBSR subjects 
and SME subjects to the blinded research coordinator in a manner that does not reveal which 
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instructor the subject reported the adverse event to or any other information that would reveal 
the subject’s group assignment. To accomplish this, we will minimize the ‘discussion’ aspect of 
how the SME instructors report potential adverse events or any other information about a 
subject to the research coordinator because discussion of the report may lead to 
unblinding/may make it obvious as to which instructor it was reported to if the SME instructor 
doesn’t know much about the encounter. The SME instructors will simply state e.g. “Participant 
ID 123 has reported <a symptom or potential adverse event or other information worded in a 
manner that does not reveal the subject’s group assignment> to an instructor.” The research 
coordinator will then follow up with the subject via phone for formal adverse event 
documentation. If indicated, the research coordinator will complete an Adverse Event form. 
Similarly, any subject-specific information that the research coordinators need to communicate 
to the instructors will go through the SME instructors, and then the SME instructors will pass the 
information along to the MBSR instructors if the subject is in the MBSR group. 
Blinded research team members will not participate in any of the study MBSR or SME sessions.
Subject Expectancy: To minimize the influence of subjects’ expectations, subjects will be 
informed that the study is designed to test the effects of two different types of stress reduction 
programs, one of which is combined with health education. Subjects will be informed that they 
will be asked to participate in one or more of the following activities during the study sessions: 
breathing exercises, meditation, stretching exercises or health education activities. Further, 
subject expectancy will be assessed at the baseline, 2-month, and 6-month, study visits using a 
Stress Reduction Expectancy Scale (SRES) modified from the Acupuncture Expectancy Scale.
MBSR Intervention and Stress Management Education (SME) control: 
Once subjects are assigned to a study group, they will participate in 14 MBSR or SME control 
sessions:

Orientation session that will last 1 and a half to 2 hours depending on the duration of the 
individual participant interviews (1 session). 
o
Subjects will be informed that they must attend the Orientation session to 
continue in the study. If a subject misses the Orientation session after being 
randomized, the subject’s instructor will contact the subject and offer them an 
individual Orientation session. If a subject does not complete Orientation after 
being randomized to MBSR or SME, the SME instructor will notify the research 
coordinator and the subject will be withdrawn from the study.

Class #1 to 8: These sessions are once a week during the first 8 weeks, starting 
approximately 1 week after Orientation. The duration for each of these sessions will be 2 
and a half to 3 hours (8 sessions).

Retreat: A single longer MBSR or SME session that will last 7 hours (1 session)

Booster sessions #1 to 4: These are 45-minute long MBSR or SME sessions every month in 
Months 3, 4, 5 and 6 (4 sessions). 
All MBSR and SME sessions will be delivered online by experienced instructors in a live 
interactive virtual classroom using videoconferencing (PSU Zoom). Participants will be asked 
to find a place in their homes where they will not be disrupted during the sessions. 
MBSR and SME sessions will be held in small groups. The number of sessions will be the 
same in MBSR and SME to control for instructor attention and group support.
Attendance will be recorded at each session (See above section on Attendance). Subjects 
will be instructed to let their instructor know if they need to be excused from a session. It is 
possible that for some unforeseen reason a subject misses a session. If this happens, the subject 
may not be able to make the session up, but they will be encouraged to continue to follow along 
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with the home practice and do their best to attend all the remaining sessions that they are assigned 
to (See above section on “Procedures for when a subject misses a session”).
After Class #5: Subjects will be sent a link from REDCap to complete the MBSR or SME 
Midway Check-in form.
After Class #8: Subjects will be sent a link from REDCap to complete the MBSR or SME Final 
Class Assessment form.
After Class #8, subjects will start receiving emails inviting them to participate in additional 
MBSR or SME Retreat sessions and monthly booster sessions. The monthly booster sessions in 
months 3 to 6 (Booster sessions #1 to 4) are required sessions for the study. The remaining booster 
sessions, and any additional Retreat sessions after Class #8, are optional sessions subjects may 
choose to participate in if they wish. Attendance will be recorded at these additional sessions, 
however subjects will not receive any financial compensation for participating in the optional 
sessions. By keeping subjects informed of additional MBSR or SME booster and Retreat sessions 
after Class #8, these emails will be important for subject retention in the study.
We will be comparing MBSR alone versus SME alone. The MBSR group will not receive SME. The 
SME group will not receive any mindfulness. 
MBSR and SME Home Practice: Subjects in both the MBSR and SME groups will be asked to do at 
least 25 to 30 minutes of home practice per day for 6 out of 7 days per week. Positive clinical 
outcomes and high adherence have been reported with 25 to 30 minutes per day of MBSR home 
practice, which is a common adaptation to the standard 45 minutes per day of MBSR home 
practice.
Home practice in MBSR will consist of mindfulness activities in accordance with the 
standard MBSR curriculum. Home practice in SME will consist of listening to excerpts of 
audiobooks about general stress management or nutrition facts.
Instructors will assign home practice for the first 7 weeks of MBSR and SME, starting 
after Class #1. There will be no home practice assignments after Class #8, however after Class #8 
subjects will be encouraged to continue their home practice activities regularly on their own. 
The Daily Diary survey will be administered daily throughout the study to measure the type and 
quantity of home practice. 
MBSR intervention group: Subjects randomized to MBSR will receive the 8-week University of 
Massachusetts MBSR curriculum (Santorelli et al., 2017), adapted for live online delivery due to 
the COVID-19 pandemic, followed by live online mindfulness booster sessions every month in 
Months 3 to 6. The University of Massachusetts MBSR curriculum was selected for the 
intervention as it is the most standardized and researched mindfulness program that has been 
shown to reduce psychological distress in various patient populations (Kabat-Zinn, 1990). Any 
updates to the University of Massachusetts MBSR curriculum will be implemented as soon as 
they become available, and it will be documented at what point in the study they were 
implemented. To optimize delivery of MBSR in the proposed study, the MBSR sessions will be 
led by Donald McCown, PhD, MAMS, MSS, LSW, or another experienced MBSR instructor (e.g. 
Holly Socolow) who will receive regular supervision from Dr. McCown. Dr. McCown is the first 
author of “Teaching Mindfulness: A Practical Guide for Clinicians and Educators” (McCown et al., 
2010). Prior to leading MBSR sessions in the study, MBSR instructors will have completed the 
University of Massachusetts MBSR Practice Teaching Intensive or its equivalent. Additionally, 
the study MBSR instructors have been provided with resources to supplement their teacher 
training with meditation safety and trauma informed mindfulness, including the Meditation 
Safety Toolbox (https://www.brown.edu/research/labs/britton/resources/meditation-safety-
toolbox) and Trauma-Sensitive Mindfulness (https://davidtreleaven.com/).
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Outline of MBSR Booster Sessions:
•
Minutes 1 to 10 - Socializing
•
Minutes 11 to 20 - Didactic on topic based on MBSR (Instructors will keep a log 
of topics discussed with dates)
•
Minutes 21 to 35 - Mindfulness practice
•
Minutes 36 to 45 - Discussion regarding practice
Stress Management Education (SME) control group: Subjects randomized to the SME control 
group will receive Dr. Elizabeth Hoge's Stress Management Education (SME) program, adapted 
for live online delivery due to the COVID-19 pandemic. Stress Management Education was 
specifically created as a control condition for MBSR studies so it matches MBSR for time, social 
support, homework, etc. (Hoge et al., 2013). Stress Management Education does not have any 
mindfulness in it. The instructors for the SME sessions will have prior experience working with 
groups and they will be trained by Dr. Hoge to teach SME in the study. Dr. Hoge will continue to 
be available throughout the study in case any questions arise about SME. The SME program 
includes nutrition (which will be adapted for the diabetes population), exercise as gentle 
stretching with Theraband to match yoga in MBSR, and other general health topics that may be 
relevant to the diabetes population such as sleep, time management, etc. Homework for the 
SME control group will be excerpts of audiobooks about general stress management or nutrition 
facts. The SME control group will follow a manualized intervention, be optimized in its appeal to 
subjects, and have regular supervision and facilitator buy-in just like the MBSR group, as is 
recommended for active controls for MBSR studies (MacCoon et al., 2012). The SME control 
group will not involve any mindfulness. 
Subjects in both the MBSR and SME groups will have received the same general written 
guidelines on diet and exercise at their baseline study visit, consisting of two handouts 
downloaded from the American Diabetes Association Patient Education Library: (1) “Plan Your 
Portions” Diabetes Placemat  and (2) “The Diabetes Advisor - Physical Activity.” All subjects will 
have also received handouts on Hyperglycemia and Hypoglycemia, as well as Glucometer Best 
Practices and Blood Glucose Meter Correlation, at their baseline study visit. This will be the only 
information that will be the same across both groups. The MBSR group will not receive any 
additional health education other than these handouts. Throughout the duration of the study, 
the SME control group’s education on diet and physical activity will not include mindfulness, but 
will be focused on physical benefits. Only the MBSR group will engage in mindful walking and 
yoga, and mindful eating, which involves bringing awareness to emotions, cognitions, and 
physical sensations while engaged in these activities. For participants unable to walk, 
appropriate adjustments and modifications can be made.
Subject Adherence: 
Adherence to the intervention will be emphasized to all subjects. Those who cannot commit 
with reasonable certainty to the intervention will not be randomized. If a subject thinks they will 
miss the Orientation, or if they think they will miss more than 2 classes during the first 8 weeks 
(including Class #1 to 8 and the Retreat), they will be encouraged to wait for another 
wave/cohort when they are able to make the time commitment. Attendance will be recorded at 
each MBSR or SME control session as described in the section above entitled “Attendance.” In 
addition, adherence may be reflected in changes in mindfulness which will be assessed with the 
validated Toronto Mindfulness Scale (TMS; 13 items).
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Feasibility will be determined by successful recruitment and retention of subjects in the study. 
Successful delivery of MBSR will be demonstrated through increased measures of mindfulness 
(TMS) in the MBSR group, and the daily MBSR home practice log (Daily Diary survey). The TMS 
will be particularly useful in assessing subject’s mastery of MBSR skills 
Retention of Subjects: 
We will use the following strategies to keep subjects engaged throughout the 6 months of the 
study. 
We will offer a new cohort of MBSR and SME control classes approximately every 3 months (4 
times a year). We do not anticipate subjects waiting more than 3 months to start a class, except 
over the summer when wait time may be slightly longer due to vacations and scheduling 
challenges. We will keep potential study subjects engaged from the start by providing them with 
the dates and times for the next cohort of classes. Providing the dates and times of the classes 
early on will keep potential subjects engaged and it will also allow them to plan ahead and begin 
to make room in their schedule. 
Study visits will be scheduled as much as possible in advance, taking into account when subjects 
will be most available, especially around busy times like holidays, vacations, etc. We will also 
keep potential subjects engaged by scheduling them for screening in the 10 weeks and 2 days 
(72 days) before the start of the study intervention (Orientation). Those who meet the eligibility 
criteria and consent will be kept further engaged by scheduling them for a baseline study visit in 
the 6 weeks before the start of the study intervention (Orientation). 
Subjects will be randomized in the week before the start of the study intervention (Orientation). 
At that time, the SME instructor will contact the subject by phone to randomize them after 
answering any questions the subject may have and confirming that the subject is still available 
to participate in the study. 
The SME instructor who randomizes a subject will be the one main point person that the subject 
can contact with any questions about the study. This will be very important in building rapport 
with the subject and encouraging retention in the study. 
Research staff will contact subjects throughout the study to encourage retention, including:

The research coordinators will call subjects before each of their remote or in-person 
study visits to review instructions for the study visit and remind subjects to bring 
their smartphone, glucometer (even if not checking blood sugars frequently), other 
diabetes devices (e.g. CGM, insulin pump or other smart insulin delivery devices), 
Home A1cNow Self Check kit, accelerometer if indicated, current medication list, 
etc. The research coordinators will also ask subjects for the names of any new 
diabetes devices (glucometers, CGM, insulin pump or other smart insulin delivery 
devices) they have been using since the previous study visit so that the research 
team can plan how to collect data from the new device at the upcoming study visit.

If a subject misses a study visit, the research coordinators will call the subject to 
reschedule the study visit within the specified time window if possible, and to 
confirm the subject is still willing to come to subsequent study visits (See Overview 
of Study Visit Time Windows above in section 7.2.2).

After Class #8, subjects will start receiving emails inviting them to participate in 
additional MBSR or SME Retreat sessions and monthly booster sessions. The 
monthly booster sessions in months 3 to 6 (Booster sessions #1 to 4) are required 
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sessions for the study. The remaining booster sessions, and any additional Retreat 
sessions after Class #8, are optional sessions subjects may choose to participate in if 
they wish. Attendance will be recorded at these additional sessions, however 
subjects will not receive any financial compensation for participating in the optional 
sessions. By keeping subjects informed of additional MBSR or SME booster and 
Retreat sessions after Class #8, these emails will be important for subject retention 
in the study.

The SME instructors or unblinded research coordinators will call subjects before 
each of the required MBSR and SME booster sessions (Booster sessions #1 to 4) to 
remind subjects of the booster sessions and to encourage them to do their best to 
continue to respond to the Stress & Cravings and Daily Diary survey invitations, 
check their blood sugars as prescribed, etc.

If a subject misses an MBSR or SME session that they were assigned to, the subject 
will receive an email from their instructor. After 48 hours of the missed session, if 
the subject has not communicated with the instructors regarding the missed 
session, the SME instructor will call the subject. Subjects who miss a session will be 
encouraged to continue to follow along with the home practice and do their best to 
attend all the remaining sessions that they are assigned to. 
o
If a subject has 2 consecutive unexcused absences, the SME instructor or 
other unblinded research coordinator will contact the subject, and 
encourage the subject to continue to follow along with the home practice 
and do their best to attend the sessions.  Subjects will be advised to contact 
their instructor if they have any questions or concerns about their sessions 
or home practice.

The SME instructor or unblinded research coordinators will call subjects if the 
response rate to the Stress & Cravings or Daily Diary survey is less than 70% (or 0% 
meaning no responses at all) as described in the section above entitled “Experience 
Sampling: Daily Stress & Cravings and Daily Diary Surveys.”

Whenever possible more than one of the above can be carried out in a single phone 
call. 
At the beginning of any phone call, study visit, or other contact with a subject, blinded research 
staff will remind subjects not to say anything that would reveal their group assignment e.g. 
instructors’ names, specifics about their classes or Daily Diary survey questions, the PSU Zoom 
link for their classes, etc. 
At every contact with a subject (e.g. phone call, study visit), the research staff will encourage 
retention of the subjects by including the following principles:
1-
Appreciation: Research staff will let the subjects know that we appreciate all that 
they are doing for the study.
2-
Encouragement without judgment: Research staff will encourage subjects to attend 
all the study visits and will reassure subjects that they will not be judged if they are 
not able to check their blood sugars as prescribed or respond to all the Experience 
Sampling Surveys, or if they miss a class etc. Subjects will be encouraged to do their 
best to complete as many of the classes and study procedures as they are able to. 
3-
Purpose: We will engage all the subjects with the goals of the research and explain 
how every study visit and every study procedure they complete are very important 
in helping the research team better understand how stress affects people living 
with diabetes.
7.2.5
Visit #2 (Follow-up Phone Call after Class #4)
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Within 2 weeks after Class #4, the blinded research coordinators will call the subjects and administer the 
Stress Experience Survey and the Hypoglycemia Survey using a phone script. At the beginning of the 
phone call, the research coordinator will remind subjects not to say anything that would reveal their 
group assignment e.g. instructors’ names, specifics about their classes or Daily Diary survey questions, 
the PSU Zoom link for their classes, etc. The research coordinator will make 3 attempts to reach a 
subject for the follow-up phone call. If a subject misses the follow-up phone call within the specified 2-
week time window, the subject will not be withdrawn from the study, and their follow-up phone call 
data will be considered missing data.
7.2.6
Visit #3 (2-month Study Visit)
The 2-month study visit will be scheduled after MBSR or SME Class #8. If the 2-month visit cannot be 
completed in the CRC due to COVID-19, or the preference of the subject, the 2-month visit will be 
completed remotely using videoconferencing (PSH Teams), and all data that can be collected remotely 
will be obtained including the home hemoglobin A1c using the Home A1CNow Self Check kit, urine 
pregnancy test when applicable, diabetes device data, and surveys. At the beginning of the study visit, 
the blinded research coordinators will remind subjects not to say anything that would reveal their group 
assignment e.g. instructors’ names, specifics about their classes or Daily Diary survey questions, the PSU 
Zoom link for their classes, etc. 
Subjects will be asked to bring the following to the remote or in-person 2-month visit:

A list of their current medications and supplement so their current medications and 
supplements can be recorded 

Their smartphone if they have one

Their diabetes devices (glucometers, CGM, insulin pump and other smart insulin delivery 
devices)

Home A1cNow Self Check kit they were given at their screening or baseline visit.
At the 2-month study visit, subjects will present to the CRC after a 10-hour fast (no food or drink, except 
for water). Additionally, subjects will be asked not to eat or drink (except for water), chew gum, smoke, 
brush their teeth, exercise physically, or consume prescription or over-the-counter medications in the 
60 minutes prior to the visit (as well as during the last 60 minutes of the visit) to prepare for the 
collection of saliva samples. Subjects will be asked not to wash their hair for 24 hours before the visit, 
and not to have their hair cut to a length less than 2 cm, to prepare for the optional collection of 2 cm 
hair samples. Subjects will be asked not to clip their fingernails for at least 2 to 3 weeks prior to the visit 
to prepare for the optional clipping of approximately 2 mm of nails from each finger of both hands. 
Subjects will be asked to remove any nail polish at least 24 hours before the visit.
At the 2-month visit, the procedures in the baseline visit will be repeated as described above in section 
7.2.3 entitled “Visit #1 (Baseline Study Visit)” and in Table 3. In the CRC, a single blood sample will be 
obtained and all of the baseline laboratory measurements will be repeated. If a subject forgets to fast, 
blood will still be drawn and documentation will be made of how many hours it has been since they last 
had something to eat or drink. Saliva for cortisol and α-amylase will be collected 1) Just before the study 
visit starts, and 2) immediately after the study visit ends. Hair and nail samples (optional) will be 
collected and stored to be analyzed later for cortisol, but they will not be analyzed under this protocol. 
Physical exam will include measurement of weight, height, waist and hip circumferences, blood 
pressure, and pulse. Body composition will be measured using a Tanita scale, when possible. The 
physical exam will only be completed if the study visit is in the CRC.
All subjects will complete self-administered questionnaires as described in the baseline visit. After sitting 
quietly for 15 minutes they will first complete the Toronto Mindfulness Scale (TMS). Then they will 
complete the remaining questionnaires: Stress Reduction Expectancy Scale (SRES), Food Craving 
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Questionnaire-Trait-Reduced (FCQ-TR), Walking Enjoyment Scale, Participant Questionnaire, Diabetes 
Distress Scale (DDS), Perceived Stress Scale-10 (PSS-10), Short Form-12 (SF-12), Positive and Negative 
Affect (PANAS), GAD-7, PROMIS-Sleep Disturbance 8a, Modified Coronavirus Impact Scale, Phone Call 
Time Preference, and the safety assessment PHQ-9. The Counterfactual Measurement will not be 
administered at the 2-month visit as this questionnaire has a 6-month recall period and will only be 
administered at the baseline and 6-month study visits. 
In addition, subjects will be asked to rate their Perceived Efficacy, Satisfaction, Engagement and 
Confidence in the study sessions, on a scale of 0-10 (0 = Not at all; 5 = Moderately; 10 = Very much). 
These questions will be self-administered at the 2-month study visit (as well as at the 6-month study 
visit). These items were adapted from a previous acupuncture study (Mao et al., 2007). 
The research coordinators will administer the Stress Experience Survey and the Hypoglycemia Survey, 
collect glucometer, CGM and diabetes device data, and assist the subjects in obtaining their home 
hemoglobin A1C value from the Home A1cNow Self Check kit as described in the baseline visit. 
Additionally, the research coordinator will record whether the subjects responded to at least 70% of the 
Daily Diary and the Stress and Cravings Experience Sampling Surveys. 
At the end of the 2-month visit, a urine pregnancy test will be administered to female subjects of 
childbearing potential who do not meet any of the criteria for reasonable certainty of not being 
pregnancy as defined above in the screening visit. Any subjects found to be pregnant will be informed of 
their pregnancy test results, and then withdrawn from the study due to the effects of pregnancy on 
study outcomes. If the subject has a pregnancy test within 2 weeks before the 2-month visit, verified in 
their medical records, the pregnancy test result can be accepted in lieu of repeating the test at the 2-
month visit. If the study visit is conducted remotely, and if a pregnancy test result collected within 2 
weeks before the study visit is not available, then the subject will be mailed a urine pregnancy test to 
complete at this visit. Subjects will communicate their urine pregnancy test result to the study team by 
showing the research coordinator their pregnancy test result as displayed on their urine pregnancy test 
kit during the ( PSH Teams) live videoconferencing study visit. If the pregnancy test is positive, the 
subject will be withdrawn from the study. 
At the 2-month visit, the research coordinators will provide subjects with an optional Actigraph device 
to wear around their waist for 7 days after the visit. If the 2-month visit is conducted remotely, the 
optional Actigraphs will be mailed to the subject. Subjects will be asked to mail the Actigraph back to the 
study team, after the 7 day wear time, in a pre-stamped envelope, along with a wear time log/diary. In 
the 2 weeks after Class #8, subjects will receive email invitations from the research coordinator to 
complete two optional ASA24 dietary recalls (1 weekend and 1 weekday) about their food intake on the 
previous day.
If a study visit is conducted remotely, or if a subject misses a study visit, the research coordinator will 
obtain and record any available diabetes device data and outside lab results, including hemoglobin A1c, 
glucose and Lipid panel.
7.2.7
Visit #4 (6-month Study Visit/End of Study Visit)
The 6-month study visit will be scheduled after MBSR or SME Booster session #4 (end of study). If the 6-
month visit cannot be completed in the CRC due to COVID-19, or the preference of the subject, the 6-
month visit will be completed remotely using videoconferencing (PSH Teams) and all data that can be 
collected remotely will be obtained including the home hemoglobin A1c using the Home A1CNow Self 
Check kit, urine pregnancy test when applicable, diabetes device data, and surveys. At the beginning of 
the study visit, the blinded research coordinators will remind subjects not to say anything that would 
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reveal their group assignment e.g. instructors’ names, specifics about their classes or Daily Diary survey 
questions, the PSU Zoom link for their classes, etc. 
Subjects will be asked to bring the following to the remote or in-person 6-month visit:

A list of their current medications and supplements so their current medications and 
supplements can be recorded 

Their smartphone if they have one

Their diabetes devices (glucometers, CGM, insulin pump and other smart insulin delivery 
devices) 

Home A1cNow Self Check kit they were given at their screening or baseline visit

The optional Actigraph device and wear time log/diary that was mailed to them before this visit 
so that they could wear the Actigraph for 7 days before the final visit
At the 6-month study visit, subjects will present to the CRC after a 10-hour fast (no food or drink, except 
for water). Additionally, subjects will be asked not to eat or drink (except for water), chew gum, smoke, 
brush their teeth, exercise physically, or consume prescription or over-the-counter medications in the 
60 minutes prior to the visit (as well as during the last 60 minutes of the visit) to prepare for the 
collection of saliva samples. Subjects will be asked not to wash their hair for 24 hours before the visit, 
and not to have their hair cut to a length less than 2 cm, to prepare for the optional collection of 2 cm 
hair samples. Subjects will be asked not to clip their fingernails for at least 2 to 3 weeks prior to the visit 
to prepare for the optional clipping of approximately 2 mm of nails from each finger of both hands. 
Subjects will be asked to remove any nail polish at least 24 hours before the visit.
At the 6-month visit, the procedures in the baseline visit will be repeated as described above in section 
7.2.3 entitled “Visit #1 (Baseline Study Visit)” and in Table 3. In the CRC, a single blood sample will be 
obtained and all of the baseline laboratory measurements will be repeated. If a subject forgets to fast, 
blood will still be drawn and documentation will be made of how many hours it has been since they last 
had something to eat or drink. Saliva for cortisol and α-amylase will be collected 1) Just before the study 
visit starts, and 2) immediately after the study visit ends. Hair and nail samples (optional) will be 
collected and stored to be analyzed later for cortisol, but they will not be analyzed under this protocol. 
Physical exam will include measurement of weight, height, waist and hip circumferences, blood 
pressure, and pulse. Body composition will be measured using a Tanita scale, when possible. The 
physical exam will only be completed if the study visit is in the CRC.
All subjects will complete self-administered questionnaires as described in the baseline visit. After sitting 
quietly for 15 minutes they will first complete the Toronto Mindfulness Scale (TMS). Then they will 
complete the remaining questionnaires: Stress Reduction Expectancy Scale (SRES), Food Craving 
Questionnaire-Trait-Reduced (FCQ-TR), Walking Enjoyment Scale, Participant Questionnaire, Diabetes 
Distress Scale (DDS), Perceived Stress Scale-10 (PSS-10), Short Form-12 (SF-12), Positive and Negative 
Affect (PANAS), GAD-7, PROMIS Sleep Disturbance 8a, Modified Coronavirus Impact Scale, the safety 
assessment PHQ-9, and Counterfactual Measurement. In addition, questions about Perceived Efficacy, 
Satisfaction, Engagement and Confidence in the study sessions will be self-administered at the 6-month 
study visit as described in the 2-month study visit.
The research coordinators will administer the Stress Experience Survey and the Hypoglycemia Survey, 
collect glucometer, CGM and diabetes device data, and assist subjects in obtaining their home 
hemoglobin A1c value from the Home A1cNow Self Check kit as described in the baseline visit.
At the end of the 6-month visit, a urine pregnancy test will be administered to female subjects of 
childbearing potential who do not meet any of the criteria for reasonable certainty of not being 
pregnant as defined above in the screening visit. Any subjects found to be pregnant will be informed of 
their pregnancy test results. If the subject has a pregnancy test within 2 weeks before the 6-month visit, 
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verified in their medical records, the pregnancy test result can be accepted in lieu of repeating the test 
at the 6-month visit. If the study visit is conducted remotely, and if a pregnancy test result collected 
within 2 weeks before the study visit is not available, then the subject will be mailed a urine pregnancy 
test to complete at this visit. Subjects will communicate their urine pregnancy test result to the study 
team by showing the research coordinator their pregnancy test result as displayed on their urine 
pregnancy test kit during the ( PSH Teams) live videoconferencing study visit. 
Before the 6-month visit, the research coordinators will mail subjects an optional Actigraph device to 
wear around their waist for 7 days before the visit. Subjects will be asked to return the Actigraph and 
wear time log/diary at the 6-month visit. If this visit is conducted remotely, subjects will be asked to mail 
the Actigraph back to the study team, after the 7 day wear time, in a pre-stamped envelope, along with 
a wear time log/diary. In the 2 weeks before Booster #4, subjects will be emailed by the research 
coordinator and asked to complete two optional ASA24 dietary recalls (1 weekend and 1 weekday) 
about their food intake on the previous day.
If a study visit is conducted remotely, or if a subject misses a study visit, the research coordinator will 
obtain and record any available diabetes device data and outside lab results, including hemoglobin A1c, 
glucose and Lipid panel.
7.3
Duration of Participation
The duration of an individual subject’s participation in the study will be approximately 6 to 8-1/2 
months.
8.0
Subject Numbers and Statistical Plan
8.1
Number of Subjects
The number of subjects expected to be enrolled and screened is no more than 520 subjects in order to 
reach the randomization target of 290 subjects. To assure reaching the study’s planned sample size 
requirement (of 290) we will randomize no more than 320 subjects in total. 
8.2
Sample size determination
The primary outcome for this trial is the absolute difference between the two interventions with respect 
to the mean change in hemoglobin A1c from baseline to month 6 and we consider an absolute 
difference of 0.5% in this outcome to be clinically meaningful. As this is an individually randomized 
group treatment trial, correlation among observations within groups (defined here as class cohort), as 
measured by the intraclass correlation coefficient (ICC), must be taken into consideration (Pals et al., 
2008). The variance inflation factor, or design effect, for this type of trial will inflate the sample size by 
1+(1-m)ρ, where m is the average group size and ρ is estimated by the ICC. For both interventions 
(MSBR and SME), we plan to have the average group size be 18 subjects and expect the ICC=0.08. Thus, 
the design effect is 2.36. Furthermore, we anticipate that 15% of the subjects will drop-out of the study 
prior to completion. Incorporating the design effect of 2.36 and the anticipated 15% drop-out, a sample 
size of 290 subjects (145/intervention) will provide 80% power to detect a clinically meaningful 0.5% 
absolute difference between the two interventions with respect to the mean change in hemoglobin A1c 
from baseline to month 6, assuming a standard deviation of 0.9% (Frias et al., 2011) using a two-sided 
test having a significance level of 0.05.
8.3
Statistical methods
Data (i.e., physiologic, behavioral, diabetes-related distress, and mindfulness) will be collected 
longitudinally in this trial. The time period of primary interest in this trial is the change from baseline to 
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6-months. Linear mixed effects models, which are subject-specific models, will be fit and contrasts 
constructed to assess adjusted changes from baseline between interventions over time with respect to 
these continuous outcomes (e.g., the primary outcome of hemoglobin A1c). The primary contrast of 
interest is the change in an outcome from baseline to month 6 between the two interventions. 
However, contrasts will also be constructed to assess the change in an outcome from baseline to other 
points in time (e.g., month 2) between the two interventions to gauge, for example, if the intervention is 
effective at month 2. The independent fixed factors for the mixed-effects models will include 
intervention, time (e.g., baseline, 2 months, 6 months),  the randomization stratification factor of insulin 
vs. non-insulin treated at baseline, and the interaction of intervention with time. The group (class 
cohort) the participant is assigned will be a nested random effect (i.e., group/class cohort will be nested 
within intervention) in the mixed-effects models to account for the correlation among observations 
within groups (class cohorts) inherent in an individually randomized group treatment trial (Pals et al., 
2008; Murray et al., 2004). Each class cohort will be characterized by various class sizes, instructors, etc. 
and thus will be important to account for throughout the duration of the trial wherever possible. The 
time factor in the models for the vast majority of the outcomes will consist of measurements taken at 
baseline, 2 months, and 6 months, per subject. An unstructured variance-covariance matrix will be 
pursued to assess the residual error associated with the repeated measurements over time per 
participant. If this variance-covariance structure fails to provide model convergence, then others will be 
explored. Linear mixed-effects models are an extension of ordinary regression models that account for 
the between- and within-subject correlation inherent in longitudinal trials. Mixed-effects models also 
appropriately handle the correlation within groups for individually randomized group treatment trials by 
specifying these groups as random effects. Residual diagnostics will be used to determine the 
appropriateness of model fit and, if necessary, transformations (e.g., logarithmic) of the outcome will be 
performed to meet modeling assumptions. If transformations fail to provide adequate model fit then 
adding splines to the linear mixed-effects models, or using nonlinear mixed-effects models, will be 
considered.
Following our assessment of the initial fit of the models, we will add covariates to the models to assess 
their impact, if any, on the intervention outcome effects. Some of the covariates to potentially be 
considered at baseline include biological sex, age, BMI, race, ethnicity, education, income, Adverse 
Childhood Experiences (ACEs), trial expectations/reasons for joining the trial, marital status, work status, 
type of diabetes, number of years with diagnosed diabetes and whether insulin-treated or non-insulin 
treated.  We will also explore potential effects of diabetes-related medication changes that took place 
during the trial that could have impacted the outcome measure at-hand (and/or self-reported 
adherence to prescribed diabetes medications). As many diabetes patients take medications to lower 
their HbA1c, this will be an important factor to control for during analysis. 
We will follow the principle of intention-to-treat for all primary analyses. In other words, we will include 
the data on each randomized participant in the statistical analyses, regardless of whether that 
participant was fully engaged in the study (e.g. participants who were randomized and withdrew prior to 
starting their randomized allocation, participants who remained active in the study but were not fully 
compliant in attending their randomized allocation study sessions, level of home practice engagement, 
etc.). Secondary analyses may explore subgroups of subjects with higher engagement and/or 
compliance with their study sessions (e.g. subjects who attended at least 8 out of the first 10 sessions). 
We may use the observed data to determine if/how participants who completed the study differed from 
those who did not.  Statistical methods to account for differential dropout will be considered, if 
applicable. 
Method to Assess Potential Mediating Effects 
For the primary outcome of hemoglobin A1c, we want to ensure that potential mediators (e.g. stress) 
are considered so that the effect of the MBSR intervention on the primary outcome is appropriately 
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estimated. Various measures of stress (and other potential mediators) are collected throughout the 
study longitudinally using questionnaires and surveys at each of the study visits (Baseline, 2MO, 6MO). 
Using the generalized linear regression methods presented by VanderWeele (2014), the overall effect on 
the primary outcome of the change in hemoglobin A1c will be decomposed into 4 components: (1) the 
controlled direct effect (CDE) due to MBSR intervention, (2) the reference interaction (IRF) between the 
MBSR intervention and the mediator, (3) the mediated interaction (IMD) between the MBSR 
intervention and the mediator, and (4) the pure indirect effect (PIE) due to the mediator. Dividing each 
of these components by the total effect provides the corresponding proportion contributions of these 
components. These 4 components will provide insight into how much of the total overall effect is: (a) 
due to neither mediation nor interaction (i.e., CDE), (b) due to interaction (i.e., IRF), (c) due to both 
mediation and interaction (i.e., IMD), and (d) due to mediation (i.e., PIE). Other potential mediators of 
the primary outcome will be assessed similarly, and additional exploratory subgroup analyses may be 
performed to explore these potentially mediating effects whenever necessary. The plan is to use SAS 
PROC CAUSALMED.
All hypothesis tests will be two-sided and we will invoke a 0.05 two-sided significance level for all 
primary and secondary statistical analyses. As our analyses are based upon defined hypotheses, we have 
not included corrections for multiple testing. While the issue of p-value adjustment for multiple testing 
has long been a topic of discussion in observational epidemiology and clinical trials, it generally is 
accepted that p-values should not be the sole criterion for assessing relationships. Conclusions will be 
based on the preponderance of scientific evidence related to each hypothesis, considering point 
estimates and confidence intervals, as well as statistical significance. Nonetheless, findings with marginal 
statistical significance will be interpreted cautiously, taking into consideration a type I error. Further, we 
deem that interim statistical analyses are not necessary for this trial, so we will not pursue such 
analyses. All analyses will be performed using SAS software, version 9.4 (SAS Institute, Inc., Cary, NC), R 
software, version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria), or Stata software, 
version 13 (StataCorp LP, College Station, TX). 
9.0
Data and Safety Monitoring Plan
9.1
Periodic evaluation of data
Interim statistical analyses of primary and secondary outcomes are not necessary for this trial and will 
not be performed. 
9.2
Data that are reviewed
Recruitment, enrollment, retention, demographics, subject status, adherence to study intervention, 
patient-reported safety assessments and Adverse Events data will be reviewed. See Data and Safety 
Monitoring Plan in Appendix.
9.3
Method of collection of safety information
For this study, we adapted recent recommendations and resources provided by Dr. Willoughby Britton, 
an external consultant with expertise in the adverse effects of mindfulness-based interventions, and 
updated the adverse event (AE) collection and reporting methods, and the CRFs for tracking and 
tabulating adverse events, that we used in our previous NIH-funded mindfulness study. Additionally, Dr. 
Britton recently updated the National Center for Complementary and Integrative Health (NCCIH) DSMP 
template v.3.0 to meet CONSORT Harms Criteria, which we used as a guide to update our DSMP 
(Ioannidis et al., 2004). 
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Adverse events will be recorded at each study visit (the baseline study visit, follow-up phone call after 
Class #4, 2-month study visit, and 6-month study visit) and throughout the study whenever subjects or 
their instructors initiate reporting of an adverse event. Within 24 hours, adverse events in participants 
assigned to MBSR will be reported via phone or email by Dr. McCown from West Chester University (or 
other study MBSR instructor e.g. Holly Socolow) to the SME instructors to maintain blinding. Within 24 
hours, adverse events in all participants (MBSR and SME) will be reported via phone or email by the SME 
instructor to the blinded research coordinator and the overall study PI Dr. Raja-Khan at the primary site 
at Hershey. The SME instructor will communicate adverse events (e.g. requiring a change in MBSR or 
SME practice recommendations), and other information about MBSR subjects and SME subjects, to the 
blinded research coordinator and to Dr. Raja-Khan in a manner that does not reveal which instructor the 
subject reported the adverse event to, or any other information that would reveal the subject’s group 
assignment. To accomplish this, we will minimize the ‘discussion’ aspect of how the SME instructors 
report the AE, or any other information about a subject, to the research coordinator because discussion 
of the report may lead to unblinding/may make it obvious as to which instructor it was reported to if the 
SME instructor doesn’t know much about the encounter. The SME instructor will simply state e.g. 
“Participant ID 123 has reported <a symptom or potential adverse event or other information worded in 
a manner that does not reveal the subject’s group assignment> to an instructor.” The research 
coordinator will then follow up with the subject via phone for formal AE documentation. If indicated, the 
research coordinator will complete an Adverse Event form. 
All subjects will be followed up to 6 months. Adverse events will be followed for outcome information 
until resolution or stabilization.  Adverse events will also be entered in the REDCap database.
Adverse Event Forms will be completed for each adverse event that a subject experiences (See Data and 
Safety Monitoring Plan in Appendix). Severity and expectedness will be determined using a specific set 
of external criteria provided by Dr. Britton who is independent from the study team and does not have a 
conflict of interest (See Severity Grading Tool and Dr. Britton’s List of Previously-Reported Meditation 
Effects). These external criteria include precise definitions for severity and expectedness. The 
descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse 
Events (CTCAE) version 5.0 will also be utilized for AE reporting 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm). We will use Dr. 
Britton’s List of Previously-Reported Meditation Effects to determine whether the symptom is an 
expected effect, and to determine the symptom Domain out of 8 domains including a Diabetes Domain 
in addition to Dr. Britton’s 7 domains (Affective, Cognitive, Conative, Perceptual, Sense of Self, Social, 
and Somatic).  This is in-line with CONSORT harms guidelines as it improves precision and reduces 
subjectivity around the assessment of severity and expectedness.
Furthermore, the Stress Experience Survey which includes questions about the most common 
meditation-related symptoms and other stress-related symptoms, will be administered by the research 
coordinator at the baseline study visit, follow-up phone call after Class #4, 2-month study visit, and 6-
month study visit. Additionally to allow for corrective feedback during the MBSR course, subjects will be 
sent a link from REDCap to complete a Midway Check-in questionnaire after Class #5 so that instructors 
can adjust mindfulness practice recommendations when indicated based on subjects’ responses.
The research coordinator will administer a Hypoglycemia Survey at the baseline study visit, follow-up 
phone call after Class #4, 2-month study visit, and 6-month study visit. The Hypoglycemia Survey will ask 
about self-reports of Level 2 hypoglycemia (glucose < 54 mg/dL) and Level 3 hypoglycemia 
(hypoglycemia requiring the assistance of another person for treatment). Level 2 hypoglycemia will be 
recorded as an Adverse Event. Level 3 hypoglycemia will be recorded as a Serious Adverse Event (see 
DSMP).
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The Principal Investigator will confirm that all adverse events (AE) are correctly entered into the AE case 
report forms by the coordinator; be available to answer any questions that the coordinators may have 
concerning AEs; and will notify the IRB, NIH, CRC/CTSI and DSMB of all applicable AEs as appropriate. All 
assessments of AEs will be made by a licensed medical professional who is an investigator on the 
research team.
The Research Coordinator will complete the appropriate report form and logs; assist the PI to prepare 
reports and notify the IRB, NIH, CRC/CTSI and DSMB of all Unanticipated Problems/Serious Adverse 
Events (SAEs). See Data and Safety Monitoring Plan in Appendix.
9.4
Frequency of data collection
All data collection will begin immediately upon enrollment. Study accrual, subject retention, subject 
adherence to intervention sessions, and study safety will be reviewed by the DSMB every 6 months (and 
more frequently if needed) starting 6 months after randomization of the first cohort. The PHQ-9 will be 
administered at the baseline study visit, 2-month study visit, and 6-month study visit to screen for 
depression and suicide. The Stress Experience Survey which includes questions about the most common 
meditation-related symptoms and other stress-related symptoms, will be administered by the research 
coordinator at the baseline study visit, follow-up phone call after Class #4, 2-month study visit, and 6-
month study visit. Additionally, to allow for corrective feedback during the MBSR course, subjects will be 
sent a link from REDCap to complete a Midway Check-in questionnaire after Class #5 so that instructors 
can adjust mindfulness practice recommendations when indicated based on subjects’ responses. The 
research coordinator will also administer a Hypoglycemia Survey at the baseline study visit, follow-up 
phone call after Class #4, 2-month study visit, and 6-month study visit. See Data and Safety Monitoring 
Plan in Appendix.
9.5
Individuals reviewing the data
See Data and Safety Monitoring Plan in Appendix.
9.6
Frequency of review of cumulative data
See Data and Safety Monitoring Plan in Appendix.
9.7
Statistical tests
Not applicable
9.8
Suspension of research
This study will be stopped prior to its completion if: (1) the intervention is associated with adverse 
effects that call into question the safety of the intervention; (2) difficulty in study recruitment or 
retention will significantly impact the ability to evaluate the study endpoints; (3) any new information 
becomes available during the trial that necessitates stopping the trial; or (4) other situations occur that 
might warrant stopping the trial.
The PI will include an assessment of futility in the annual progress report to NIH and will consult with the 
study monitors and the NIH Program Official to assess the impact of significant data loss due to 
problems in recruitment, retention, or data collection.
10.0
Risks
Risks of Stress Reduction Programs
Meditation-related risks: NCCIH states that meditation is generally safe for healthy people, but that adverse 
effects have also been reported (NCCIH, 2018). Undesirable side effects and risks of meditation have been 
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documented in more than 40 scientific reports [for reviews see (Lindahl et al., 2017; Lustyk et al. 2009; Kuijpers et 
al., 2007; Baer et al, 2019; Britton, 2019; Van Dam et al., 2018)] and are listed in Mindfulness-Based Program 
Guidelines (Kuyken et al., 2012; Santorelli et al., 2017). More common, less serious side effects that have been 
reported by individuals within the context of mindfulness-based interventions (MBIs) or who are meditating less 
than an hour of daily practice include: increased depression, anxiety or panic, re-experiencing of traumatic 
memories, dissociation, executive dysfunction, headaches/body pain and insomnia (Lindahl et al., 2017; Lomas et 
al., 2014; Cebolla et al., 2014; Brooker et al., 2013; Johnson et al., 2016; Reynolds et al., 2017; Britton et al., 2010). 
A few case reports of more serious side effects including mania, psychosis, and suicidality have been reported, 
mostly in the contexts of intensive retreats (>5 hrs/day) or in conjunction with pre-existing psychopathology 
(Lindahl et al., 2017; Kuijpers et al., 2007; Kuyken et al., 2012; Yorston, 2001). The frequency of serious adverse 
effects in the context of MBIs is estimated to be less than 1%, although adequate estimates are not available 
(Wong et al., 2018). The frequency of non-serious Adverse Events with mild-moderate impairment in functioning is 
unknown; available estimates range from 1-25% (Baer et al., 2019).  
To minimize this risk, we will monitor subjects’ levels of distress during the study and use trained instructors who 
are experienced in detecting when participants of their MBSR class are experiencing increased distress and then 
providing appropriate corrective feedback e.g. adjustment of MBSR practice, referral to a mental health specialist, 
etc. Subjects will be monitored for the most common meditation-related symptoms and other stress-related 
symptoms with the Stress Experience Survey at the baseline study visit, follow-up phone call after Class #4, 2-
month study visit, and 6-month study visit. Additionally, subjects will be monitored at each study visit for 
worsening depressive symptoms and suicidal thinking using the Patient Health Questionnaire-9 (PHQ-9). Subjects 
with suicidal ideation will be referred to one of the following appropriate resources for immediate evaluation:
1.
Dr. Dahlia Mukherjee (cell 775-351-9927)
2.
Dr. Erika Saunders (pager 2292, cell 717-514-3818)
3.
Psychiatric consult  
Additional resources for meditation-related adverse effects, including dissociation:

The study MBSR instructors Holly Socolow and Dr. Donald McCown

Co-Investigators Dr. Jeffery Greeson and Dr. Elizabeth Hoge

External consultant Dr. Willoughby Britton
Risks of Exercise
During the study treatment sessions subjects may be asked to perform gentle stretching and other light exercises. 
There are risks inherent to any exercise program. Such risks include, but are not limited to, risk of slip, trip, fall, 
and bodily injury. The instructors will work with subjects to minimize these risks.
Risks of Hypoglycemia
The Oxford Mindfulness Centre’s “Mindfulness-Based Cognitive Therapy (MBCT) Exclusion Criteria Explained” 
document in the Meditation Safety Toolbox 
(https://www.brown.edu/research/labs/britton/resources/meditation-safety-toolbox) lists insulin-treated 
diabetes as a potential issue that they have found can limit or prevent people from benefitting from their public 
MBCT courses. According to this document, which is addressed to potential participants, for people with insulin-
dependent diabetes: “During periods of meditation the body may become relaxed and for some people, over time, 
meditation reduces stress. This may in turn have an effect on blood glucose and insulin requirements and may 
potentially result in a need for adjustments to pattern of insulin administration and dosage. Please let your GP or 
other healthcare professional know that you are doing the course and discuss this possibility with them.” 
People with diabetes are at risk for hypoglycemia when they start any new exercise or lifestyle program, especially 
if they are on insulin or insulin secretagogues. This does not mean that exercise and lifestyle programs are 
contraindicated in diabetes. On the contrary, due to their numerous benefits, exercise and lifestyle programs are 
strongly encouraged in people with diabetes, with monitoring of blood glucose levels and adjustment of 
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medication doses as needed. Therefore, diabetes should not be considered an absolute contraindication to 
mindfulness. 
To minimize the risk of hypoglycemia, as we do with any exercise or lifestyle program, we will inform subjects that 
if they are on certain diabetes medications, such as insulin or a sulfonylurea, they may be at risk for hypoglycemia 
(blood glucose less than 70 mg/dL) during or after the stress reduction sessions or home practice due to the 
effects of stress reduction or exercise on blood glucose. Regardless of the medications subjects are on, they will be 
advised to check their blood glucose before and after each stress reduction session and home practice (and during 
long or intense stress reduction sessions or home practice). They will be advised to carry the following items with 
them at all times, including at their study visits and stress reduction sessions: their glucometer, testing supplies, 
and carbohydrate-rich foods such as juice, hard candies or glucose tablets to treat hypoglycemia if it occurs. If they 
have glucagon, they will be advised to also carry it with them at all times. They will be provided written guidelines 
about how to monitor for, treat, and prevent hypoglycemia. They will be advised to ask their physician for 
instructions on adjusting their diabetes medications, if needed, when participating in the stress reduction sessions, 
or doing home practice. 
Subjects will be advised of possible signs and symptoms of hypoglycemia which may include: 
- Headache
- Irritability
- Nervousness or feeling anxious
- Hunger
- Weakness
- Fast heartbeat
- Dizziness or light-headedness
- Sweating
- Confusion
- Feeling shaky or jittery 
- Sleepiness
- Loss of consciousness if left untreated
In a joint position statement of the American Diabetes Association (ADA) and the European Association for the 
Study of Diabetes, the International Hypoglycaemia Study Group recommends the following proposed glucose 
cutoffs when reporting the frequency of hypoglycemia in clinical trials of glucose-lowering drugs, as well as of non-
pharmacological interventions, for the treatment of diabetes mellitus (International Hypoglycemia Study Group, 
2017):
Level 1: A glucose alert value of 70 mg/dL or less. This need not be reported routinely in clinical studies, 
although this would depend on the purpose of the study.
Level 2: A glucose of < 54 mg/dL is sufficiently low to indicate serious, clinically important hypoglycemia 
Level 3: Severe hypoglycemia, as defined by the ADA denotes severe cognitive impairment requiring the 
assistance of another person for treatment (Workgroup on Hypoglycemia, ADA, 2005; Seaquist et al., 2013).
Therefore, the research coordinator will administer a Hypoglycemia Survey at the baseline study visit, follow-up 
phone call after Class #4, 2-month study visit, and 6-month study visit. The Hypoglycemia Survey will ask about 
self-reports of Level 2 and Level 3 hypoglycemia. Level 2 hypoglycemia will be recorded as an Adverse Event. Level 
3 hypoglycemia will be recorded as a Serious Adverse Event (see DSMP). 
Subjects will be advised to have 911 called if they ever have severe hypoglycemia, which is when they are having 
symptoms that are keeping them from being able to treat hypoglycemia themselves and they require the 
assistance of another person to treat their hypoglycemia. They will be advised to contact their physician and the 
study team if they ever have a glucose less than 54 mg/dL or hypoglycemia requiring the assistance of another 
person to treat.  They will be advised to contact their physician if their blood glucose level ever drops below their 
goal during the night or upon awakening, or if their blood glucose level frequently drops below their goal at other 
times of the day.  
Risks of Fasting
The risks of fasting include feeling light-headed, dizzy or faint. If subjects are on certain diabetes medications, such 
as insulin or a sulfonylurea, they may be at risk for hypoglycemia while fasting for the study visits, and their 
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medications may need to be adjusted when they are fasting. They will be advised to ask their physician for 
instructions on adjusting their diabetes medications, if needed, while fasting. 
Risks of Venipuncture
The discomfort associated with removing blood by venipuncture (by needle from a vein) is a slight pinch or pin 
prick when the sterile needle enters the skin. The risks include mild discomfort and/or a black and blue mark at 
the site of puncture. Less common risks include a small blood clot, infection or bleeding at the puncture site, and 
on rare occasions fainting during the procedure. To minimize discomfort from blood sampling, the amount of 
blood we will remove will be 60 mL (4 tablespoons) or less. 
Risks of Randomization
Subjects will be randomly assigned to one of two different stress reduction programs. The study stress reduction 
program a subject receives may prove to be less effective or to have more side effects than the other study stress 
reduction program or other available treatments.
Risks of Loss of Confidentiality
There is a risk of loss of confidentiality if subjects’ information or their identity is obtained by someone other than 
the investigators, but precautions will be taken to prevent this from happening. The confidentiality of subjects’ 
electronic data created by the subject or by the researchers will be maintained as required by applicable law and 
to the degree permitted by the technology used. Absolute confidentiality cannot be guaranteed.
During the study stress reduction sessions, all participants will be instructed to keep all conversations occurring 
during the sessions completely confidential. Furthermore, subjects will be reassured that they are not required to 
answer any questions or reveal any information that they do not want to.
Risks of Questionnaires
Subjects may get tired or bored when we are asking them questions or they are completing questionnaires or 
responding to Experience Sampling Surveys. Subjects will be reassured that they do not have to answer any 
question they do not want to answer.
The potential psychological risks of completing the BRFSS ACE and CTQ questionnaires are minimal. As is 
recommended, we preface these questionnaires by informing subjects beforehand that some of the questions 
may make them feel uncomfortable, and they are free to skip any of the questions they do not want to answer. 
These types of questionnaires are commonly completed by study participants, and our study personnel will be 
able to appropriately respond to any stress responses. If patients feel uncomfortable, we will help them process 
through it so that they are ok by the end of the study visit. 
Risks of High Blood Glucose
The study stress reduction programs are not expected to increase subjects’ blood glucose levels. However, it is 
possible that in the process of collecting subjects’ glucose data from their glucometers, CGM and other diabetes 
devices, we become aware of hyperglycemia (increased blood glucose level). Subjects will be provided written 
guidelines about how to monitor for and prevent hyperglycemia. Subjects will be advised to contact their 
physician if their blood glucose levels are persistently elevated above their goal. In the event of severe 
hyperglycemia (blood glucose level persistently over 350 mg/dL), subjects will be referred to the Emergency 
Department at Milton S. Hershey Medical Center, or a local Emergency Department, for immediate evaluation. 
Unforeseen Risks
There may be unknown risks or risks that we cannot predict associated with being in this research. It is possible 
that the study procedures could detect a possible unknown medical problem that is unrelated to the purpose of 
this study.  If the research procedures uncover findings that may be important for subjects to know about, such as 
the possibility of a previously unknown medical condition, a member of the study team will contact the subject to 
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find out if they would like to learn more. These findings may require additional testing or treatment.  The cost of 
any additional tests or related treatment will be the subject’s responsibility.
The Data and Safety Monitoring Board (DMSB), an independent group of experts, will be reviewing the 
information from this research throughout the study.  If any important new information about the study develops 
that may affect subjects’ health, welfare, or willingness to stay on the study, the PI will inform the subjects, and 
the subjects may be asked to sign another consent form at that time.
11.0
Potential Benefits to Subjects and Others 
11.1
Potential Benefits to Subjects
Subjects in the MBSR group may benefit from increased awareness of their feelings and thoughts about 
their diabetes, reduced subjective stress, improved quality of life and overall well-being, and possibly 
better blood glucose control and reduced risk for diabetes complications. Subjects in the SME group may 
benefit from health education about general stress management, nutrition, and exercise. Although all of 
these benefits are possible, they cannot be guaranteed. Most importantly, the potential benefits of 
MBSR and the risks of continuing to ignore stress in patients with uncontrolled diabetes outweigh the 
minimal risks associated with doing the proposed study.
11.2
Potential Benefits to Others
The results of this research may guide the future treatment of diabetes. The knowledge gained from the 
proposed study may help researchers to develop effective comprehensive treatment programs for 
patients with diabetes that address both the mind and the body to reduce stress, improve glucose 
control and other key health outcomes, and optimize overall health and wellbeing in patients with 
diabetes.
12.0
Sharing Results with Subjects
Subjects will receive the results of their hemoglobin A1c levels checked during the study. Hemoglobin A1c is a 
measure of average glucose levels over the past 3 months and is widely used as an assessment of glucose 
control in patients with diabetes.
13.0
Subject Payment and/or Travel Reimbursements
Subjects will be compensated $25 for completing the screening visit, $35 for completing the baseline study visit, 
$50 for completing the 2-month study visit and, $70 for completing the 6-month study visit. 
Additionally, subjects will be compensated a total of up to $105 for completing 14 MBSR or SME sessions 
(Orientation, Class #1 to 8, Retreat, and Booster sessions #1 to 4) as $5 per session for the first 5 sessions they 
attend, $8 per session for the next 5 sessions they attend, and $10 per session for the next 4 sessions they 
attend. The money for completing the sessions will be given to the subjects at the 2-month study visit and 6-
month study visit. 
Finally, subjects will be compensated a total of $15 if they respond to at least 70% of the Experience Sampling 
Surveys (both Stress and Cravings and Daily Diary) by their 2-month study visit. 
The total amount subjects will receive for participation in this research study is up to $300. If subjects do not 
complete the study for any reason, they will be paid for the study visits and stress reduction sessions they have 
completed.
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14.0
Economic Burden to Subjects
14.1
Costs
The costs to subjects include their time, and travel if study visits are conducted in-person.
14.2
Compensation for research-related injury
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Costs for the treatment of research-related injuries 
will be charged to subjects or their insurance carriers.
15.0
Resources Available 
15.1
Facilities and locations
Study visits and procedures will be carried out at the Clinical Research Center at the Penn State Health 
Hershey Medical Center when open and available, or remotely via PSHTeams. The MBSR and SME 
intervention sessions will be delivered remotely via PSU Zoom by instructors at Penn State University 
and Westchester University of Pennsylvania. 
15.2
Feasibility of recruiting the required number of subjects
The study team has access to more than 29,000 patients with diabetes who are potential subjects for 
the study (7,385 through Endocrinology clinics, 8,784 through Internal Medicine clinics, and 13,032 
through Family Medicine clinics). Only 1% of these potential subjects (290 subjects) need to be 
recruited. The PI Dr. Raja-Khan has a proven track record of randomizing 86 women with overweight 
and obesity, including women with diabetes, prediabetes and polycystic ovary syndrome in her previous 
mindfulness study. Additionally, as an endocrinologist Dr. Raja-Khan has a clinical practice with many 
patients with uncontrolled diabetes. We have submitted an Enterprise Information Management data 
request using TriNetx, which has identified over 5,000 patients that meet our study criteria. Finally, our 
team includes Dr. Legro who has expertise in the conduct of numerous multicenter clinical trials.  
15.3
PI Time devoted to conducting the research
Through the Penn State College of Medicine Physician-Scientist Effort Matching Program, Dr. Raja-Khan 
will have a total of 50% effort to devote to this research (25% effort will be provided by the NIH for this 
R01 and 25% effort will be matched by the College of Medicine and the Department of Medicine). Dr. 
Raja-Khan is also the PI of a Department of Medicine Innovation Pilot Award, but this is a much smaller 
pilot study of only 34 subjects. Dr. Raja-Khan is in clinic one half-day per week.  Therefore, Dr. Raja-Khan 
will have sufficient time to devote to conducting and completing this research. 
15.4
Availability of medical or psychological resources
If applicable, medical or psychological resources will be provided at the Penn State Health Hershey 
Medical Center.
15.5
Process for informing Study Team
The project will be governed by a steering committee (SC) with Dr. Raja-Khan as Chair and Dr. Legro  as 
Vice Chair (they will be responsible for the recruitment, management, and safety of subjects in the trial 
along with co-investigators). The SC will consist of all the funded investigators and research coordinator 
and meet weekly as part of their regularly scheduled research meeting.  These weekly meetings provide 
a platform for study updates, training and valuable information for the ongoing conduct of the trial.
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16.0
Other Approvals
16.1
Other Approvals from External Entities
A Reliance Agreement with West Chester University of Pennsylvania will be obtained prior to engaging 
Dr. McCown to teach MBSR in the research study.
16.2
Internal PSU Committee Approvals
Check all that apply:
  Anatomic Pathology – Penn State Health only – Research involves the collection of tissues or use of 
pathologic specimens. Upload a copy of “HRP-902 - Human Tissue For Research Form” in CATS IRB. 
  Animal Care and Use – All campuses – Human research involves animals and humans or the use of 
human tissues in animals
  Biosafety – All campuses – Research involves biohazardous materials (human biological specimens 
in a PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA 
or gene therapy).
  Clinical Laboratories – Penn State Health only – Collection, processing and/or storage of extra tubes 
of body fluid specimens for research purposes by the Clinical Laboratories; and/or use of body fluids 
that had been collected for clinical purposes but are no longer needed for clinical use. Upload a copy 
of “HRP-901 - Human Body Fluids for Research Form” in CATS IRB. 
  Clinical Research Center (CRC) Advisory Committee – All campuses – Research involves the use of 
CRC services in any way.
  Conflict of Interest Review – All campuses – Research has one or more of study team members 
indicated as having a financial interest.
  Radiation Safety – Penn State Health only – Research involves research-related radiation 
procedures. All research involving radiation procedures (standard of care and/or research-related) 
must upload a copy of “HRP-903 - Radiation Review Form” in CATS IRB. 
  IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or 
intends to hold the IND or IDE.
  Scientific Review – Penn State Health only – All investigator-written research studies requiring 
review by the convened IRB must provide documentation of scientific review with the IRB 
submission. The scientific review requirement may be fulfilled by one of the following: (1) external 
peer-review process; (2) department/institute scientific review committee; or (3) scientific review by 
the Clinical Research Center Advisory committee.  NOTE: Review by the Penn State Health Cancer 
Institute (PSCI) Protocol Review Committee or the PSCI Disease Team is required if the study 
involves cancer prevention studies or cancer patients, records and/or tissues. For more information 
about this requirement see the IRB website.
17.0
Multi-Site Study
 
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17.1
Other sites
West Chester University of Pennsylvania (West Chester, PA)
Site PI: Donald McCown, PhD, MAMS, MSS, LSW
Associate Professor, Health
Director, Center for Contemplative Studies Coordinator, Graduate Certificates in Applied 
Mindfulness & Integrative Health Coordinator, Undergraduate Minor in Contemplative Studies 
West Chester University
700 S. Church Street
Ehinger Office Annex, rm 102
West Chester, PA 19383
C: 215.913.8866
Email: DMcCown@wcupa.edu
Qualifications: Dr. McCown is an Associate Professor of health, director of the minor in contemplative 
studies, and director of the center for contemplative studies at West Chester University of Pennsylvania. 
He holds a Master of Applied Meditation Studies degree from the Won Institute of Graduate Studies, a 
Master of Social Service from Bryn Mawr College, and a PhD in Social Science from Tilburg University. He 
trained as an MBSR teacher through the Center for Mindfulness at University of Massachusetts and at 
Thomas Jefferson University. His primary research interests include the pedagogy of mindfulness in 
clinical applications and higher education, applications of complementary and integrative medicine in 
the community, and the contemplative dimensions of the health humanities. He is author of The Ethical 
Space of Mindfulness in Clinical Practice, primary author of Teaching Mindfulness: A Practical Guide for 
Clinicians and Educators, New World Mindfulness: From the Founding Fathers, Emerson, and Thoreau to 
your Personal Practice, and primary editor of Resources for Teaching Mindfulness: An International 
Handbook.
IRB: Due to the NIH Single IRB Mandate, Penn State will serve as the single IRB and review the study at 
each site.
17.2
Communication Plans
The overall study PI Dr. Raja-Khan will maintain regular communication with the other sites through 
remote videoconferencing meetings with West Chester University and University Park every 2 weeks. 
Dr. McCown at West Chester University will attend these meetings, where Dr. Raja-Khan will update the 
other sites with the most current version of the protocol and consent document, and ensure that all 
modifications have been communicated to the sites. Any problems with the research, interim results 
and closure of the study will also be discussed during these meetings. Due to the NIH Single IRB 
Mandate, Penn State will serve as the single IRB and review the study at each site. 
17.3
Data Submission and Security Plan
At the end of each MBSR and SME session, unblinded research team members will record study 
participant attendance in REDCap. Attendance will be recorded in REDCap in a way that does not reveal 
group assignments to blinded research team members. All sites will safeguard data as required by Penn 
State IRB information security policies.
17.4
Subject Enrollment
Not applicable. Subject enrollment and randomization will not take place at West Chester University. 
Subject enrollment will only take place at the primary site at Hershey. Randomization will be performed 
by the SME instructors as they are unblinded. Dr. McCown at West Chester University (or other study 
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MBSR instructor e.g. Holly Socolow) will teach MBSR to study participants randomized to MBSR via 
remote videoconferencing (PSU Zoom). The SME instructors will teach SME to study participants 
randomized to SME via remote videoconferencing ( PSUZoom).
17.5
Reporting of Adverse Events and New Information
Within 24 hours, adverse events in participants assigned to MBSR will be reported via phone or email by 
Dr. McCown from West Chester University (or other study MBSR instructor e.g. Holly Socolow) to the 
SME instructors to maintain blinding. Within 24 hours, adverse events in all participants (MBSR and 
SME) will be reported via phone or email by the SME instructor to the blinded research coordinator and 
the overall study PI Dr. Raja-Khan at the primary site at Hershey. 
The SME instructor will communicate adverse events (e.g. requiring a change in MBSR or SME practice 
recommendations), and other information about MBSR subjects and SME subjects, to the blinded 
research coordinator and to Dr. Raja-Khan in a manner that does not reveal which instructor the subject 
reported the adverse event to, or any other information that would reveal the subject’s group 
assignment. To accomplish this, we will minimize the ‘discussion’ aspect of how the SME instructors 
report adverse events, or any other information about a subject, to the research coordinator because 
discussion of the report may lead to unblinding/may make it obvious as to which instructor it was 
reported to if the SME instructor doesn’t know much about the encounter. The SME instructor will 
simply state e.g. “Participant ID 123 has reported <a symptom or potential adverse event or other 
information worded in a manner that does not reveal the subject’s group assignment> to an instructor.” 
The research coordinator will then follow up with the subject via phone for formal adverse event 
documentation. If indicated, the research coordinator will complete an Adverse Event form.
17.6
Audit and Monitoring Plans
We will hold weekly team meetings and biweekly whole study group meetings to ensure all local site 
investigators conduct the study appropriately. The research coordinator will conduct random monthly 
audits of study materials at each site to ensure compliance. 
18.0
Adverse Event Reporting
18.1
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) experienced 
by a subject or other individual, which in the opinion of the investigator is determined to be (1) 
unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures.
19.0
Study Monitoring, Auditing and Inspecting
19.1
Auditing and Inspecting
The investigator will permit study-related monitoring, audits, and inspections by the Penn State quality 
assurance program office(s), IRB, the sponsor, and government regulatory bodies, of all study related 
documents (e.g., source documents, regulatory documents, data collection instruments, study data etc.).  
The investigator will ensure the capability for inspections of applicable study-related facilities (e.g., 
pharmacy, diagnostic laboratory, etc.).
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20.0
Future Undetermined Research: Data and Specimen Banking
20.1
Data and/or specimens being stored
For participants who provide written consent to bio-banking, excess specimens not used in this study 
will be placed in a biorepository for future research with related health information. Bio-banking will be 
completed by the Penn State Institute for Personalized Medicine (IPM) and will be linked to participant 
medical/demographic data through a unique identification number assigned by The Penn State 
Personalized Research for Innovation, Discovery, and Education (PRIDE) Program (PRAMS00040532). 
Medical and demographic data collected for the currently proposed study will be stored by the IPM per 
the PRIDE protocol for future use with bio-banked samples. Specimens within the IPM will be labeled 
with a second layer Study ID.
All samples collected prior to 8/1/2021 will be under the direction of the PRIDE protocol. The samples 
that are collected after 8/1/2021 will be stored in the IPM, but the samples cannot be released to other 
investigators using the PRIDE Protocol unless the participant signs a PRIDE Consent.
20.2
Location of storage
Banked specimens will be stored on the PS HMC campus in C2706.
20.3
Duration of storage
Specimens and data will be stored indefinitely.
20.4
Access to data and/or specimens
Access to specimens collected under the current study will be limited to the PI and select members of 
the IPM staff.  
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21.0
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22.0
Confidentiality, Privacy and Data Management 
See the Research Data Plan Review Form
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Data and Safety Monitoring Plan (DSMP) – v.04/29/2022
I. Study Identification Information
A.
NIH Study Number― 5R01DK119379-03 
B.
NIH Study Title― Randomized Controlled Trial of a Six-Month Mindfulness-Based Intervention for 
Diabetes 
C.
Name of Principal Investigator (PI)― Nazia T. Raja-Khan, M.D., M.S. 
II. Study Overview
A. Brief Description of the Purpose of the Study― The overall goal of this project is to compare the 
effectiveness of a six-month Mindfulness-based stress reduction (MBSR) intervention versus stress 
management education (SME) in improving glucose control and other important outcomes in patients 
with uncontrolled diabetes (HbA1c ≥7.5%). 
B. Adherence Statement― The Data Safety Monitoring Board Chair will carry out this Data Safety 
Monitoring Plan (DSMP) independent of the study and in adherence to the protocol approved by the 
Penn State Hershey IRB.
Dr. Willoughby Britton’s updates to the National Center for Complementary and Integrative 
Health (NCCIH) DSMP template v.3.0 to meet CONSORT Harms Criteria were adapted in this DSMP 
(Ioannidis et al., 2004). 
III. Confidentiality
A.  Protection of Subject Privacy
During this study, all of the materials (e.g., biometric data, surveys, biologic specimens) collected are 
for research purposes only, and data will be kept in strict confidence. No information will be given to 
anyone without permission from the subject. Confidentiality will be ensured by use of identification 
codes. All data, whether generated in the laboratory or at the study visit, will be identified with an 
identification code unique to the subject.
B. Database Protection 
The database will be secured with password protection. The informatics manager will receive only 
coded information that is entered into the database under those identification numbers. Electronic 
communication with outside collaborators will involve only unidentifiable information. Source documents 
including all paper and electronic records for all enrolled subjects, i.e., case report forms, laboratory 
reports, subject study binders, etc. will also be secured. Electronic source documents will be secured 
with password protection. Paper source documents will be kept in locked files in the Investigators’ 
academic office.
As part of the Penn State Clinical and Translational Science Institute (CTSI), Penn State is a member of 
the Research Electronic Data Capture (REDCap) Consortium. Study data, including questionnaires and 
lab data, will be managed using REDCap which is a secure web application designed to support data 
capture for research studies, providing user-friendly web-based case report forms, real-time data entry 
validation (e.g., for data types and range checks), audit trails and a de-identified data export 
mechanism to common statistical packages (SPSS, SAS, Stata, R/S-Plus). The data management 
system will allow research staff to register participants, generate participant visit schedules, enter data, 
edit entry errors, and determine entry status of participant forms. Database access for REDCap is 
granted on a study-by-study basis. At the start of the trial when the database is created all research 
personnel will be given defined user roles and assigned a unique username and password. Using the 
REDCap database management application, each new participant will be registered into the trial 
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registry. The registry will assign a unique identification (ID) number to the participant that links his/her 
data across multiple tables. REDCap allows for data type and range checks at the point of data entry 
and provides clear alerts for valid entry ranges or types. In addition to the range checks built into 
REDCap at the point of data entry, extreme outliers and missing data for our primary and secondary 
outcomes as well as baseline demographic and clinical characteristics will be queried by the 
biostatisticians prior to data analysis to ensure completeness and accuracy of our reported data. 
REDCap was developed by a multi-institutional consortium, which includes Penn State, and was 
initiated at Vanderbilt University. The database is hosted at the Penn State Health Hershey Medical 
Center and College of Medicine data center, which will be used as a central location for data processing 
and management.
The research coordinator, who is blinded to group assignment, will enter the subject data into the 
REDCap database. The SME instructors, who are not involved in the collection or analysis of 
outcomes, will randomize subjects using the REDCap randomization module. The REDCap 
randomization module will be set up so that only the SME instructor or other unblinded research staff 
members who need to access randomization information will have role rights and exporting rights to 
ensure blinding.
C. Confidentiality During Adverse Event (AE) Reporting 
AE reports and annual summaries will not include subject or group-identifiable material unless 
requested by the DSMB due to safety concerns. Each report will only include the identification code.
IV. Adverse Event Information
A.  Definition 
An adverse event (AE) is any untoward medical occurrence in a subject temporally associated with 
participation in the clinical study or with use of the experimental agent being studied. An adverse finding 
can include a sign, symptom, abnormal assessment (laboratory test value, vital signs, 
electrocardiogram finding, etc.), or any combination of these.
A Serious Adverse Event (SAE) is any AE that results in one or more of the following outcomes:

Death

A life-threatening event

Inpatient hospitalization or prolongation of existing hospitalization 

A persistent or significant disability/incapacity

A congenital anomaly or birth defect

Important medical event based upon appropriate medical judgment
B. Classification of AE Severity 
AEs will be labeled according to severity, which is based on their impact on the patient. Severity grade 
will be determined as 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Very Severe, or 5 = Death according to 
the Common Terminology Criteria for Adverse Events (CTCAE) and other sources for grading the 
severity of adverse events. Severity seriousness will be determined as Serious or Not Serious. 
Seriousness, which requires a different reporting procedure is defined according to the Office for 
Human Research Protections, Guidance on Reviewing and Reporting Unanticipated Problems 
Involving Risks to Subjects or Others and Adverse Events (Linden, 2013; OHRP, 2007; NCI, 2017). 
These classifications will be determined using a specific set of external criteria with precise definitions 
provided by Dr. Willoughby Britton who is independent from the study team and does not have a 
conflict of interest (See Severity Grading Tool in Appendix C1). The descriptions and grading scales 
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found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will 
also be utilized for AE reporting 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm).
C. AE Attribution Scale (Relatedness)
To assess the relationship of an event to the study intervention, the following guidelines are used:
1.
Related (Possible, Probable, Definite)
a.
The event is known to occur with the study intervention.
b.
There is a temporal relationship between the intervention and event onset.
c.
The event abates when the intervention is discontinued.
d.
The event reappears upon a re-challenge with the intervention.
2.
Not Related (Unlikely, Not Related)
a.
There is no temporal relationship between the intervention and event onset.
b.
An alternate etiology has been established.
AEs will be categorized according to the likelihood that they are related to the study intervention. 
Specifically, they will be labeled as “0 = Not related, 1 = Unlikely related, 2 = Possibly related, 3 = 
Probably related, or 4 = Definitely related. Additionally, we will use Dr. Britton’s List of Previously-
Reported Meditation Effects (See Appendix C2) to determine whether the symptom is an expected 
effect, and to determine the symptom Domain out of 8 domains including a Diabetes Domain (See 
Appendix D) in addition to Dr. Britton’s 7 domains (Affective, Cognitive, Conative, Perceptual, Sense of 
Self, Social, and Somatic). 
 
Relatedness to treatment will be assessed according to 8 causality and relatedness criteria that 
regulatory agencies such as the World Health Organization (WHO), the Federal Drug Administration 
(FDA), and the National Institutes of Health (NIH) use to make health policy decisions (NIH, 2016; 
Agbabiaka et al., 2008; Turner, 1984; WHO, 2016). These criteria are designed to assess treatment-
relatedness in individual cases in the absence of prospective or epidemiological (base rate) data. The 8 
standard causality/relatedness criteria are 1) prior published reports, and expert judgment, 2) subjective 
attribution, 3) temporal proximity (challenge), or  exacerbation, 4) consistency, 5) dose-response 
gradient 6) de-challenge, 7) re-challenge, 8) specificity, (Turner, 1984; Naranjo, 1986; Naranjo, 1982; 
Naranjo, 1981; Hill, 1965; Hill, 2015; Gallagher et al., 2011; Theophile et al., 2010). 
The Relatedness Criteria Definitions table below provides detailed definitions for assessing relatedness 
in individual cases.
Relatedness Criteria Definitions Table
1. Previous 
Reports/known 
effects and expert 
judgment
Symptom has been previously reported in association with 
meditation or judged to be caused by meditation by 
experts (meditation teachers/clinicians)
2. Subjective attribution
Participant thinks symptom was caused by meditation
3.  Temporal proximity 
OR Exacerbation
Symptom occurred for the first time OR
pre-existing symptoms got worse during/following treatment
4.  Consistency
More than one occasion following meditation
5.  Dose/gradient
Symptom was worse with higher dose of treatment 
6.  De-challenge
Decreased when stopped meditation
7.  Re-challenge
Re-appeared or increased when meditation restarted
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8. Specificity 
Presence of plausible alternative cause: Something other 
than meditation (medical illness, life event, substances) 
could account for symptom (meditation played no causal 
role).
D. Expected Risks 
Expected risks to the subject are as follows:
o
Inserting a needle for blood sampling can be associated with some discomfort and bruising, 
and very rarely with inflammation and infection of the arm veins.
o
Loss of subject confidentiality.
These risks are considered to be minimal and are addressed in the protocol and consent form.
To minimize discomfort from blood sampling, we will require only a minimal amount of blood ~ 60 ml. 
All questionnaires and subject data forms will be coded with unique identification numbers to protect 
subject confidentiality. To reduce the risk of breaching confidentiality, subjects will be instructed to keep 
all conversations occurring during the sessions completely confidential. Furthermore, subjects will be 
reassured that they are not required to answer any questions or reveal any information that they do not 
want to. 
Meditation-related risks: NCCIH states that meditation is generally safe for healthy people, but that 
adverse effects have also been reported (NCCIH, 2018). Undesirable side effects and risks of 
meditation have been documented in more than 40 scientific reports [for reviews see (Lindahl et al., 
2017; Lustyk et al. 2009; Kuijpers et al., 2007; Baer et al, 2019; Britton, 2019; Van Dam et al., 2018)] 
and are listed in Mindfulness-Based Program Guidelines (Kuyken et al., 2012; Santorelli et al., 2017). 
More common, less serious side effects that have been reported by individuals within the context of 
mindfulness-based interventions (MBIs) or who are meditating less than an hour of daily practice 
include: increased depression, anxiety or panic, re-experiencing of traumatic memories, dissociation, 
executive dysfunction, headaches/body pain and insomnia (Lindahl et al., 2017; Lomas et al., 2014; 
Cebolla et al., 2014; Brooker et al., 2013; Johnson et al., 2016; Reynolds et al., 2017; Britton et al., 
2010). A few case reports of more serious side effects including mania, psychosis, and suicidality have 
been reported, mostly in the contexts of intensive retreats (>5 hrs/day) or in conjunction with pre-
existing psychopathology (Lindahl et al., 2017; Kuijpers et al., 2007; Kuyken et al., 2012; Yorston, 
2001). The frequency of serious adverse effects in the context of MBIs is estimated to be less than 1%, 
although adequate estimates are not available (Wong et al., 2018). The frequency of non-serious 
Adverse Events with mild-moderate impairment in functioning is unknown; available estimates range 
from 1-25% (Baer et al., 2019). 
Because of these risks, subjects will be monitored at frequent intervals throughout the study for 
expected and unexpected Adverse Events. Risks will be further minimized by employing trained 
instructors who are experienced in detecting when participants of their MBSR class are experiencing 
increased distress and then providing appropriate corrective feedback e.g. adjustment of MBSR 
practice, referral to a mental health specialist, etc. 
The Stress Experience Survey will be administered by the research coordinator at the baseline 
study visit, follow-up phone call after Class #4, 2-month study visit, and 6-month study visit. This 
includes questions about the most common meditation-related symptoms (items 1 to 10) and a 
question about other stress-related symptoms. This survey was adapted from Dr. Willoughby Britton’s 
MBP-Specific Adverse Effects Survey (Britton_Version9.18.19), which represents the 10 most common 
meditation-related symptoms from the Varieties of Contemplative Experience Phenomenology 
Codebook (Lindahl et al., 2017), as replicated in an NIH-funded mindfulness-based intervention clinical 
trial (Britton, in prep). 
Additionally to allow for corrective feedback during MBSR, subjects will be sent a link from 
REDCap to complete a Midway Check-in questionnaire after Class #5 so that instructors can adjust 
mindfulness practice recommendations when indicated based on subjects’ responses. The study 
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MBSR instructors have been provided with resources to supplement their teacher training with 
meditation safety and trauma informed mindfulness, including the Meditation Safety Toolbox 
(https://www.brown.edu/research/labs/britton/resources/meditation-safety-toolbox) and Trauma-
Sensitive Mindfulness (https://davidtreleaven.com/).
At each study visit subjects will be screened for depressive symptoms and suicidal thinking using the 
Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 will be self-administered in REDCap at the 
screening visit, baseline visit, 2-month visit, and 6-month visit. At every study visit, the blinded research 
coordinator will review the subjects’ responses to the PHQ-9 in REDCap. If any answers are missing, 
the research coordinator will ask the subject: “Are you sure you meant to skip this question?” If the 
subject did not mean to skip the question, the research coordinator will be able to go in and enter the 
subject’s response (REDCap will track that the research coordinator entered the response).
If a subject is not comfortable with answering the 9th item of the PHQ-9 at the screening visit, 
they will be excluded from the study. If a subject refuses to answer the 9th item of the PHQ-9 at any of 
the subsequent study visits, the subject will be excluded from the study, and the research coordinator 
will immediately contact one of the below suicidality experts.
Subjects’ PHQ-9 scores at each of the study visits will be immediately calculated by REDCap, 
even if subjects refuse to answer all of the PHQ-9 questions. If a subject’s PHQ-9 score at any of the 
study visits is 10 or greater, they will be recommended to see their PCP for further evaluation. The 
research coordinator will give the subject an Incidental Findings Letter to share with their PCP. This 
letter will include the subject’s PHQ-9 score. These subjects can still continue in the study as long as 
they meet the other eligibility criteria.
If a subject scores 1 or greater on the 9th item of PHQ-9, a trained research coordinator will 
interview the subject using the modified P4 Screener to assess suicide risk (Dube et al., 2010). If the 
subject answers Somewhat Likely or Very Likely to the modified P4 Screener question which asks 
“How likely do you think it is that you will act on these thoughts about hurting yourself or ending your life 
some time over the next month?”, they are considered higher risk and will not be eligible for the study. 
For these higher risk subjects, the research coordinator will immediately contact one of the following 
appropriate suicidality experts, who will immediately evaluate the subject for suicidality and determine if 
the subject needs to be escorted to the Emergency Department because they have an active suicidal 
plan in the immediate future:
1.
Dr. Dahlia Mukherjee (cell 775-351-9927)
2.
Dr. Erika Saunders (pager 2292, cell 717-514-3818)
3.
Psychiatric consult  
If on the modified P4 Screener, the subject answers Not at all Likely to “How likely do you think 
it is that you will act on these thoughts about hurting yourself or ending your life some time over the 
next month?” and they answer No to “Is there anything that would prevent or keep you from harming 
yourself?” the research coordinator will ask “You said ‘Not at all Likely’ to Q5. What is stopping you 
from acting on harming yourself?” If the subject provides a response to what is stopping them from 
acting on harming themself, they can continue in the study as long as they meet the other eligibility 
criteria. If the subject cannot provide a response to what is stopping them from acting on harming 
themself, the subject will be considered higher risk and excluded from the study, and the research 
coordinator will immediately contact one of the above suicidality experts.
If the subject refuses to answer any of the modified P4 Screener questions at any of the study 
visits, they will be excluded, and the research coordinator will immediately contact one of the above 
suicidality experts.
 
The Oxford Mindfulness Centre’s “Mindfulness-Based Cognitive Therapy (MBCT) Exclusion Criteria 
Explained” document in the Meditation Safety Toolbox 
(https://www.brown.edu/research/labs/britton/resources/meditation-safety-toolbox) lists insulin-treated 
diabetes as a potential issue that they have found can limit or prevent people from benefitting from their 
public MBCT courses. According to this document, which is addressed to potential participants, for 
people with insulin-dependent diabetes: “During periods of meditation the body may become relaxed 
and for some people, over time, meditation reduces stress. This may in turn have an effect on blood 
glucose and insulin requirements and may potentially result in a need for adjustments to pattern of 
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insulin administration and dosage. Please let your GP or other healthcare professional know that you 
are doing the course and discuss this possibility with them.” 
People with diabetes are at risk for hypoglycemia when they start any new exercise or lifestyle 
program, especially if they are on insulin or insulin secretagogues. This does not mean that exercise 
and lifestyle programs are contraindicated in diabetes. On the contrary, due to their numerous benefits, 
exercise and lifestyle programs are strongly encouraged in people with diabetes, with monitoring of 
blood glucose levels and adjustment of medication doses as needed. Therefore, diabetes should not be 
considered an absolute contraindication to mindfulness. 
To minimize the risk of hypoglycemia, as we do with any exercise or lifestyle program, we will 
inform subjects that if they are on certain diabetes medications, such as insulin or a sulfonylurea, they 
may be at risk for hypoglycemia (blood glucose less than 70 mg/dL) during or after the stress reduction 
sessions or home practice due to the effects of stress reduction or exercise on blood glucose. 
Regardless of the medications subjects are on, they will be advised to check their blood glucose before 
and after each stress reduction session and home practice (and during long or intense stress reduction 
sessions or home practice). They will be advised to carry the following items with them at all times, 
including at their study visits and stress reduction sessions: their glucometer, testing supplies, and 
carbohydrate-rich foods such as juice, hard candies or glucose tablets to treat hypoglycemia if it occurs. 
If they have a glucagon, they will be advised to also carry it with them at all times. They will be provided 
written guidelines about how to monitor for, treat, and prevent hypoglycemia. They will be advised to 
ask their physician for instructions on adjusting their diabetes medications, if needed, when 
participating in the stress reduction sessions, or doing home practice. 
In a joint position statement of the American Diabetes Association (ADA) and the European 
Association for the Study of Diabetes, the International Hypoglycaemia Study Group recommends the 
following proposed glucose cutoffs when reporting the frequency of hypoglycemia in clinical trials of 
glucose-lowering drugs, as well as of non-pharmacological interventions, for the treatment of diabetes 
mellitus (International Hypoglycemia Study Group, 2017):
Level 1: A glucose alert value of 70 mg/dL or less. This need not be reported routinely in clinical 
studies, although this would depend on the purpose of the study.
Level 2: A glucose of < 54 mg/dL is sufficiently low to indicate serious, clinically important 
hypoglycemia 
Level 3: Severe hypoglycemia, as defined by the ADA denotes severe cognitive impairment 
requiring the assistance of another person for treatment (Workgroup on Hypoglycemia, ADA, 2005; 
Seaquist et al., 2013).
Therefore, the research coordinator will administer a Hypoglycemia Survey at the baseline study 
visit, follow-up phone call after Class #4, 2-month study visit, and 6-month study visit. The 
Hypoglycemia Survey will ask about self-reports of Level 2 and Level 3 hypoglycemia. Level 2 
hypoglycemia will be recorded as an Adverse Event. Level 3 hypoglycemia will be recorded as a 
Serious Adverse Event. 
Subjects will be advised to have 911 called if they ever have severe hypoglycemia, which is 
when they are having symptoms that are keeping them from being able to treat hypoglycemia 
themselves and they require the assistance of another person to treat their hypoglycemia. They will be 
advised to contact their physician and the study team if they ever have a glucose less than 54 mg/dL or 
hypoglycemia requiring the assistance of another person to treat.  They will be advised to contact their 
physician if their blood glucose level ever drops below their goal during the night or upon awakening, or 
if their blood glucose level frequently drops below their goal at other times of the day.  
In the event of severe hyperglycemia recognized upon downloading subjects’ glucometers, subjects 
will be referred to the Emergency Department at Milton S. Hershey Medical Center, or a local 
Emergency Department, for immediate evaluation. 
E. Adverse Events Reporting and Follow-Up 
Adverse events will be recorded at each study visit (the baseline study visit, follow-up phone call after 
Class #4, 2-month study visit, and 6-month study visit) and throughout the study whenever subjects or 
their instructors initiate reporting of an adverse event. Within 24 hours, adverse events in participants 
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assigned to MBSR will be reported via phone or email by Dr. McCown from West Chester University (or 
other study MBSR instructor e.g. Holly Socolow) to the SME instructors to maintain blinding. Within 24 
hours, adverse events in all participants (MBSR and SME) will be reported via phone or email by the 
SME instructor to the blinded research coordinator and the overall study PI Dr. Raja-Khan at the 
primary site at Hershey. The SME instructor will communicate adverse events (e.g. requiring a change 
in MBSR or SME practice recommendations), and other information about MBSR subjects and SME 
subjects, to the blinded research coordinator and to Dr. Raja-Khan in a manner that does not reveal 
which instructor the subject reported the adverse event to, or any other information that would reveal 
the subject’s group assignment. To accomplish this, we will minimize the ‘discussion’ aspect of how the 
SME instructors report the AE, or any other information about a subject, to the research coordinator 
because discussion of the report may lead to unblinding/may make it obvious as to which instructor it 
was reported to if the SME instructor doesn’t know much about the encounter. The SME instructor will 
simply state e.g. “Participant ID 123 has reported <a symptom or potential adverse event or other 
information worded in a manner that does not reveal the subject’s group assignment> to an instructor.” 
The research coordinator will then follow up with the subject via phone for formal AE documentation. If 
indicated, the research coordinator will complete an Adverse Event form. 
All subjects will be followed up to 6 months. Adverse events will be followed for outcome information 
until resolution or stabilization.  Adverse events will also be entered in the REDCap database.
Adverse Events Form 
Specifically, the research coordinator will use the Adverse Events Form which includes the CTCAE and 
accompanying documents (Severity Grading Tool and List of Previously-Reported Meditation Effects in the 
Appendices, and the Relatedness Criteria Definitions Table above in section IV-C) to provide:
a) A description of the AE/SAE, including the Adverse Event/CTCAE (To document COVID-19 related 
adverse events, the CTCAE term "Infections and infestations - Other, specify" will be entered. A text 
box will branch allowing the research coordinator to specify the other condition. The research 
coordinator will enter "COVID-19" here).
b) MedDRA System Organ Class (SOC)
c)
Adverse Event Domain (as categorized in the List of Previously-Reported Meditation Effects in 
Appendix C2, and in the Diabetes Domain Expected Events in Appendix D).
d) Start and end dates 
e) Severity grading (1 = Mild, 2 = Moderate, 3 = Severe, 4 = Very Severe, 5 = Death) based on the 
CTCAE and the Severity Grading Tool (Appendix C1)
f)
Relationship to treatment (using the Relatedness Criteria Definitions Table above in section IV-C 
and the List of Previously-Reported Meditation Effects in Appendix C2). (0 = Not related, 1 = 
Unlikely related, 2 = Possibly related, 3 = Probably related, 4 = Definitely related)
g) Action taken (if any) by study team regarding study intervention (0 = None, 1 = Study intervention 
modification, 2 = Study intervention discontinued)
h) Treatment required for this adverse event (0 = None, 1 = Medication, 2 = Hospitalization, 3 = Other 
(specify):__________)
i)
Outcome of AE (as assessed after 2 weeks or next check-in time point) (1 = Resolved, 2 = 
Recovered with minor sequelae, 3 = Recovered with major sequelae, 4 = Ongoing/Continuing 
treatment, 5 = Condition worsening, 6 = Death and 7 = Unknown) 
j)
Expectedness (1 = Yes, 2 = No) (Refer to List of Previously-Reported Meditation Effects in 
Appendix C2)
k)
Seriousness (1 = Yes, 2 = No) (See Severity Grading Tool for definition of Serious Adverse Event 
(SAE); use Serious Adverse Events Form if event is Serious) 
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Serious Adverse Events Form will capture:
a) The date the subject reported the SAE
b) SAE onset date (The date of onset for an SAE is the date the outcome of the AE fulfilled one of the 
serious criteria).
c)
SAE diagnosis date (In some cases this will be the same as the onset date).
d) SAE stop date
e) Description of SAE (CTCAE term) (The research coordinator will enter a symptom, condition/diagnosis 
(if available), or procedure as the primary event. If a condition/diagnosis has not been identified, the 
symptom (e.g., chest pain) will be entered, and the event will be updated to the condition/diagnosis 
when available [e.g., Cardiac Arrest]).
f)
Unexpectedness (1 = Yes, 2 = No) (Refer to List of Previously-Reported Meditation Effects in Appendix 
C2 and Diabetes Domain Expected Events in Appendix D).
g) Age of subject (at time of onset)
h) Sex of subject
i)
Brief description of the nature of the SAE (with no personal identifiers)
j)
Category of SAE (Death with date of death, Life threatening, Hospitalization-initial or prolonged with 
admission date and discharge date, Disability/incapacity, Congenital anomaly/birth defect, Required 
intervention to prevent permanent impairment, or Other:____________)
k)
Relatedness (using the Relatedness Criteria Definitions Table above in section IV-C and the List of 
Previously-Reported Meditation Effects in Appendix C2). (Unrelated [clearly not related to the 
intervention], Possible [may be related to intervention], Definite [clearly related to intervention]).
l)
Whether study intervention was discontinued due to the event? (Yes or No or N/A – event occurred 
prior to start of study intervention)
m) What medications or other steps were taken to treat the SAE? __________
n) Intervention type (Medication or nutritional supplement, Device, Surgery, Behavioral/lifestyle)
o) List any relevant tests, laboratory data, and history, including preexisting medical 
conditions:_____________
p) Is this the final report? (Yes or No)
E.1 Adverse events will be assessed according to the measures and schedule described in the table below.
Name of measure
Visit # 1
Baseline
Visit #2
Follow-up Phone Call 
after Class #4 
(Middle of 8-wk 
MBSR/SME)
Visit #3
2-month 
(End of 8-wk 
MBSR/SME)
Visit #4 
6-month
(After Booster session 
#4/End of Study)
PHQ-9
x
x
x
Stress Experience 
Survey*
x
x
x
x
Subject initiated
(passive 
monitoring)
Ongoing
Dropout-reason 
form
Ongoing, as dropouts occur
*The Stress Experience Survey, includes questions about the most common meditation-related symptoms 
and other stress related symptoms. These questions may result in the participant reporting an AE. If this 
occurs, the AE will be marked as “expected” and compared to Baseline and previous visit responses for 
proper documentation.
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E.3 Other Measures for Monitoring AEs
E.3.1 Stress Experience Survey [Adapted from Dr. Britton’s Mindfulness-based program-specific 
adverse effects (MBP-SPEC-AE) survey]. CONSORT-Harms guidelines (Ioannidis et al., 2004) recommend 
using standardized and validated scales that assess treatment-specific symptoms, because they have more 
accurate detection rates than passive monitoring (Stephens et al.,1998) or open-ended queries (Wallin and 
Sjovall, 1981; Bent et al., 2006) and are low cost, low burden and require no special training to administer. 
To accommodate these recommendations, and to create a systematic query of treatment-specific symptoms in 
all treatment arms, the research coordinator will administer the Stress Experience Survey to specifically query 
the most common meditation-related side effects (anxiety, depression, dissociation, re-experiencing of 
traumatic memories etc.) found in 8-week MBIs using patient-reported outcomes measurement information 
system (PROMIS) or NeuroQol items (or other validated scales if construct is not available). The Stress 
Experience Survey includes questions about the most common meditation-related symptoms (items 1 to 10), 
as well a question about other stress-related symptoms. This survey was adapted from Dr. Willoughby Britton’s 
MBP-Specific Adverse Effects Survey (Britton_Version9.18.19), which represents the 10 most common 
meditation-related symptoms from the Varieties of Contemplative Experience Phenomenology Codebook 
(Lindahl et al., 2017), as replicated in an NIH-funded mindfulness-based intervention clinical trial (Britton, in 
prep). Subsequently, the research coordinator will record any item occurring more frequently compared to 
baseline, or previous visit responses, as an Adverse Event and assess its severity (using the Severity Grading 
Tool in Appendix C1) and relatedness (using the Relatedness Criteria Definitions Table above in section IV-C). 
Subjects will be asked to provide further detail (i.e., date of onset, symptomology, circumstance surrounding 
the event, relatedness to the intervention, etc.) on any AE/SAE reported in the Stress Experience Survey. 
These details will be used to assess the need for treatment modification, referrals and reporting. 
E.3.2 Hypoglycemia Survey. The research coordinator will administer a Hypoglycemia Survey at the baseline 
study visit, follow-up phone call after Class #4, 2-month study visit, and 6-month study visit. The Hypoglycemia 
Survey will ask about self-reports of Level 2 hypoglycemia (glucose < 54 mg/dL) and Level 3 hypoglycemia 
(hypoglycemia requiring the assistance of another person for treatment). Level 2 hypoglycemia will be 
recorded as an Adverse Event. Level 3 hypoglycemia will be recorded as a Serious Adverse Event.
E.3.3 Subject Initiated (Passive monitoring): Subjects are encouraged to contact their instructors and/or 
study staff if any physical or mental health symptoms arise or other study-related problems occur. Subjects 
may report AEs at any time throughout the study. Events will be evaluated with the Adverse Events Form by 
study staff.
E.3.4 Attrition:  Reasons for attrition are also an important source of AEs. The research coordinator will collect 
attrition information for each dropout from the study, record the dropout date, subjects’ responses to Yes/No 
questions about general reasons for attrition that do not reveal the subjects’ group assignment, and whether 
the dropout is Subject-initiated or Investigator-initiated. 
If it is a Subject-initiated dropout or a lost to follow-up, the subject will be e-mailed a link to a REDCap 
Participant-Completed Attrition Information Survey consisting of one open ended question to elicit feedback 
about their experience in the study and learn more about their reasons for not continuing in the study. As 
subjects’ responses could reveal group assignment, the research coordinator and other blinded study team 
members will not have access to subjects’ responses to this survey in REDCap.
Investigator-initiated withdrawals: A subject may also be withdrawn from the study and/or intervention by the 
investigator. In this case, the research coordinator will record the reasons why the investigator withdrew the 
subject from the study. 
To report data on subject status, adherence/attendance at MBSR or SME classes, and attendance at study 
visits, we will use Tables 3 and 4 in Appendix A.
To report data on Adverse Events and Serious Adverse Events, we will use Tables 6 and 7 in Appendix A.
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F.  SAE Reporting
SAEs that are unanticipated, serious, and possibly related to the study intervention will be reported to 
the Data Safety Monitoring Board, Penn State IRB, Penn State CTSI, and NIH in accordance with 
requirements.  

Unexpected fatal or life-threatening AEs related to the intervention will be reported to the NIH 
Program Officer within 7 days. Other serious and unexpected AEs related to the intervention will 
be reported to the NIH Program Official within 15 days.

Anticipated or unrelated SAEs will be handled in a less urgent manner but will be reported to the 
Data Safety Monitoring Board, Penn State IRB, Penn State CTSI, NIH, and other oversight 
organizations in accordance with their requirements. 

In the AE summary of the Annual Data and Safety Monitoring Report, the Data Safety Monitoring 
Board will state that they have reviewed all AE reports.  
G. Expectedness of SAEs
The Study PI and Independent Data Safety Monitoring Board will be responsible for determining 
whether an SAE is expected or unexpected.  An event is considered expected if it appears on the List 
of Previously-Reported Meditation Effects in Appendix C2. An adverse event will be considered 
unexpected if the nature, severity, or frequency of the event is not consistent with the risk information 
previously described for the intervention.  
V. Data Quality and Safety Review Plan and Monitoring
A. Data Quality and Management
1)
Description of Plan for Data Quality and Management― The PI or study staff will review all data 
collection forms on an ongoing basis for data completeness and accuracy as well as protocol 
compliance. All data for this project will be promptly entered into a computerized database. 
Subjects will enter data directly into REDCap when completing self-administered questionnaires 
in REDCap. Research staff will enter data from paper forms into REDCap. Data can also be 
directly entered into REDCap. Subject identifications will be kept separate in locked files and will 
be destroyed when no longer needed for the project. To minimize errors, measures will be 
verified prior to data entry and computer verification will be employed during data entry. Data 
files will be backed up and archived regularly.   
2)
Frequency of Data Review for this Study― The frequency of data review for this study is 
summarized in the following Table: 
Data type
Frequency of 
review
Reviewer
Subject accrual (including accrual of minority subjects)
Every 6 months
PI, Data Safety 
Monitoring  Board
Status of all enrolled subjects, as of date of reporting 
Every 6 months
PI,  Data Safety 
Monitoring Board
Adherence data regarding study visits and intervention
Every 6 months
PI,  Data Safety 
Monitoring Board
Adverse Events (including out-of-range patient-reported 
safety assessments) 
Every 6 months
PI,  Data Safety 
Monitoring Board
SAEs
Per occurrence
PI,  Data Safety 
Monitoring Board, 
NIH, IRB, CRC/CTSI
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B. Subject Accrual and Compliance
1) Measurement and Reporting of Subject Accrual, Compliance with Inclusion/Exclusion Criteria― 
Review of the rate of subject accrual and compliance with inclusion/exclusion criteria (verifying 
that all randomized subjects meet the inclusion/exclusion criteria) will occur every 6 months to 
ensure that a sufficient number of participants are being enrolled and that they meet eligibility 
criteria and the targeted ethnic diversity goals outlined in the grant proposal (Targeted/Planned 
Enrollment Table). If recruitment goals are not being met, recruitment efforts will be targeted to 
meet any unmet goals. To report data on enrollment and subject demographics, we will use 
Tables 1 and 2 in Appendix A. 
2) Measurement and Reporting of Participant Adherence to Treatment Protocol 
Data on adherence to the treatment protocol will be collected weekly by research staff and 
reviewed every 6 months by the PI, the study statistician, and the Data Safety Monitoring Board. 
Adherence of participants will be evaluated by recording attendance at each class. Previous 
MBSR studies report adherence rates varying from 70-85%. If adherence falls below 75%, 
which might inhibit the ability of the study to test its primary hypotheses, the PI will suggest a 
conference call for study investigators to discuss methods for improving adherence.
C. Justification of Sample Size 
The goal of this study is to compare the effectiveness of a six-month MBSR intervention versus SME 
control intervention in improving glucose control and other important outcomes in patients with 
uncontrolled diabetes. The primary outcome is hemoglobin A1c, which is a measure of average glucose 
control over the past 3 months. A sample size of 290 subjects (145/group) will provide 80% power to 
detect a clinically significant 0.5% absolute difference in the mean change in A1c from baseline to 
month 6, assuming a standard deviation of 0.9%, between the two groups using a two-sided test having 
a significance level of 0.05. The sample size estimate was based on the intent-to-treat principle and 
inflated to account for the potential of 15% subject dropout. 
D. Stopping Rules 
This study will be stopped prior to its completion if: (1) the intervention is associated with adverse 
effects that call into question the safety of the intervention; (2) difficulty in study recruitment or retention 
will significantly impact the ability to evaluate the study endpoints; (3) any new information becomes 
available during the trial that necessitates stopping the trial; or (4) other situations occur that might 
warrant stopping the trial.
The PI will include an assessment of futility in the annual progress report to NIH and will consult with 
the study monitors and the NIH Program Official to assess the impact of significant data loss due to 
problems in recruitment, retention, or data collection.
E. Designation of a Monitoring Committee  
The Data Safety Monitoring Board for this study will perform the monitoring outlined in this Data and 
Safety Monitoring Plan. The independent Data Safety Monitoring Board is well qualified for this role as 
it is led by a family physician and experienced diabetes researcher, and includes a licensed clinical 
psychologist and an experienced DSMB statistician. None of the Data Safety Monitoring Board 
members are involved in this grant as key personnel. Therefore, the Data Safety Monitoring Board will 
be able to carry out this Data and Safety Monitoring Plan independent of the PI and research team. 
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F. Safety Review Plan 
Study accrual, subject retention, subject adherence to intervention sessions, and study safety will be 
reviewed by the DSMB every 6 months (and more frequently if needed) starting 6 months after 
randomization of the first study cohort. Progress reports, including patient recruitment, 
retention/attrition, and AEs will be provided to the Data Safety Monitoring Board following each of the 
reviews. An Annual Report will be compiled and will include a list and summary of AEs. In addition, the 
Annual Report will address (1) whether AE rates are consistent with pre-study assumptions; (2) reason 
for dropouts from the study (only blinded information; unblinded information from the open-ended 
attrition item will not be provided); (3) whether all participants met entry criteria; (4) whether 
continuation of the study is justified on the basis that additional data are needed to accomplish the 
stated aims of the study; and (5) conditions whereby the study might be terminated prematurely. The 
Annual Report will be sent to the Data Safety Monitoring Board and will be forwarded to the IRB, NIH, 
and other applicable recipients who will review the progress of this study on an annual basis. 
G. Study Report Outline for the Data Safety Monitoring Board (Interim or Annual Reports) 
The study team will generate Study Reports for the Data Safety Monitoring Board, and will provide 
information on the following study parameters: recruitment, enrollment, retention, demographics, 
subject status, adherence to study intervention, patient-reported safety assessments and AE data. 
Study Reports for the Data Safety Monitoring Board will not include data on primary or secondary 
endpoints as there are no interim analyses planned for the study, with the exception of safety 
outcomes. 
Study Report tables will be generated only from aggregate (not by group assignment) baseline and 
aggregate safety data for the study population. We will use the Study Report Outline in Appendix B.
VI. Informed Consent
Written informed consent will be obtained from each subject at entry into the study. Consent will be 
obtained by the research coordinator, and not the subject's physician. Potential subjects will be reassured 
that choosing not to participate will not jeopardize their medical care. Informed consent is obtained by the 
following process:
1.
The subject (If applicable, parent/guardian) will be asked to review the study consent form.
2.
The research coordinator will meet with the subject to review the form, to confirm the subject’s 
understanding of the study, and to answer any questions that the subject might have. The subject will 
have the opportunity to meet with one of the study investigators, who reviews the eligibility criteria.
3.
Once the subject demonstrates understanding of the study and agrees to participate in the study, the 
consent will be signed in the presence of the research coordinator and a witness.
VII. Reporting Changes in Study Status
During the funding of this study, any action by the IRB or one of the study investigators that results in a 
temporary or permanent suspension of the study will be reported to the NIH Program Official within 1 
business day of notification.
APPENDICES 
•
Appendix A: DSMP Study Report Figures/Tables 
•
Appendix B: DSMP Study Report Outline for the Data Safety Monitoring 
•
Appendix C1: Severity Grading Tool
•
Appendix C2: List of Previously-Reported Meditation Effects
•          Appendix D: Diabetes Domain Expected Events
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Appendix A
DSMP Study Report Figures/Tables
Figure or Table 1. Quarterly Enrollment and Randomization 
A graph or table will depict quarterly enrollment.
Quarter
#
Consented/ 
Enrolled
# Excluded (and reasons for 
excluding and ineligibility)
# 
Randomized
# Not
Randomized 
2020 Q3 (Jul-Sept)
2021 Q1 (Jan-Mar)
Total
Table 2. Demographics 
Characteristics
Enrolled Participants
Randomized Participants
Age, years
Mean (SD)
Minimum
Maximum
Sex, N (%)
Male
Female
Ethnicity, N (%)
Hispanic or Latino
Not Hispanic or Latino
Unknown
Race, N (%)
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported
Taking Insulin at Baseline Visit, N (%) 
No
Yes
Type of Diabetes, N (%)
Type 1 Diabetes
Type 2 Diabetes
Other
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Table 3. Subject Status and Class Attendance for Randomized Participants
Pt 
Iden-
tifier
Date 
Enrolled 
(Consented)
End of 
Trial Date 
Study 
Status 
(Active 
or 
Inactive) 
End of Trial 
Status 
(Completed, 
Withdrew, or 
Lost to 
Follow Up)
Total No. 
of 
Classes 
Attended 
(Max 10)
Total No. of 
Classes and 
Boosters 
Attended 
(Max 14)
 Class 
Attendance/
Adherence 
(%)
Class and 
Booster 
Attendance
/Adherence 
(%)
% Adherence to Intervention:
Note: % Adherence will be determined:
(1) when the first 10 classes the subject is assigned to ends: (#sessions attended/10)*100
(2) when all 14 of the sessions the subject is assigned to ends: (#sessions attended/14)*100
Table 4. Study Visit Attendance for Randomized Participants
Quarter
Pt Identifier
Date 
Enrolled 
(Consented)
End 
of 
Trial 
Date
Study 
Status 
(Active 
or 
Inactive) 
End of Trial 
Status 
(Completed, 
Withdrew, or Lost 
to Follow Up)
Reached 
for 4-week 
Phone 
Call
Attended 
2-month 
study 
visit
Attended
6-month 
study visit
Table 5. Out-of-Range Patient-Reported Safety Assessments in Enrolled Participants
Pt ID
Visit #
9th item of PHQ-9
(Report if ≥1)
Full PHQ-9
(Report if 
≥10)
GAD-7 
(Report if ≥10)
Higher Risk for Suicide Based 
on Modified P4 Screener? 
(Yes, No, or Not Applicable)
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Table 6. Adverse Events in Enrolled Participants
Pt 
Iden
-tifier
AE # 
for Pt
SAE 
(Yes 
or 
No)
Adverse 
Event/
CTCAE 
Term 
Other 
Term
CTCAE 
Grade
Do-
main
Start 
Date
Stop
Date
Related 
to
Study 
Inter-
vention
Action 
Taken
Out-
come
Ex-
pected
Table 7. Serious Adverse Events (including deaths) in Enrolled Participants*
Pt 
Identifier
Link 
to Pt 
AE #
Date Pt 
Reported 
 
Onset 
Date
Dx 
Date
SAE
Stop 
Date
SAE 
Category
Related 
to 
Study 
Inter-
vention
Age 
at 
Onset
Description of Actions 
and Outcomes (e.g., 
hospitalization, 
withdrawn from study)
* Adverse events will be determined to be SAEs based on the Severity Grading Tool (Appendix C1)
SAE Category: Death, Life threatening, Hospitalization-initial or prolonged, Disability/incapacity, Congenital 
anomaly/birth defect, Required intervention to prevent permanent impairment, or Other:_________________
Level 3: Severe hypoglycemia, as defined by the ADA denotes severe cognitive impairment requiring the 
assistance of another person for treatment, will be considered a SAE (Workgroup on Hypoglycemia, ADA, 
2005; Seaquist et al., 2013).
Relatedness: 0 = Not related, 1 = Unlikely related, 2 = Possibly related, 3 = Probably related, or 4 = 
Definitely related based on the the Relatedness Criteria Definitions Table above in section IV-C and the List 
of Previously-Reported Meditation Effects (Appendix C2)
Table 7. Serious Adverse Events (including deaths) in Enrolled Participants (Continued)
Pt 
ID
Link 
to Pt 
AE #
Date 
of 
Death 
 
Hospital 
Admission 
Date
Hospital 
Discharge 
Date
SAE
Other 
Catego-
ry
Unexpected
Intervention 
Discontinued 
due to SAE?
Treat-
ment 
of 
SAE
Tests, 
Labs, 
Medical 
History, 
Pre-
existing 
Medical 
Conditions
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Appendix B
DSMP Study Report Outline for the Data Safety Monitoring Board
The study team will prepare a study safety report which will begin with a brief introduction section describing 
the study status, issues, and procedures that produced the report (e.g., data obtained by specific date). A 
study description with a current timetable and study schedule will be included. Study data reports will describe 
enrollment, demographic characteristics and safety assessments. Study Report tables will be generated only 
from aggregate (not by group assignment) baseline and aggregate safety data for the study population.
Study Report Outline
I.
Table of Contents
II.
General Information
a.
Quarterly Enrollment and Randomization (see Appendix A, Figure or Table 1)
b.
Demographic Data (see Appendix A, Table 2)
c.
Subject Status (see Appendix A, Table 3)
III.
Adherence to protocol
a.
Participant Adherence to MBSR or SME/Class Attendance (see Appendix A, Table 3)
b.
Study Visit Attendance (see Appendix A, Table 4)
IV.
Safety Assessment
a.
Out-of-Range Patient-Reported Safety Assessments (see Appendix A, Table 5)
b.
Adverse Events Summary (see Appendix A, Table 6)
c.
SAE Listing including subject deaths (see Appendix A, Table 7) 
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Appendix C1
Britton_Version 11.5.18
SEVERITY GRADING TOOL
Grade
Description
 Detailed Criteria (Linden, 2013; NCI, 2017; OHRP, 2007)
1
Mild

May include transient distress and discomfort, but not enough to cause 
significant impairment, change in behavior or countermeasures.

Transient or short duration (usu. < than 1 week)

Resolved on its own; no intervention needed

No consequences
2
Moderate

Minimal, local or noninvasive intervention indicated (individual meeting with 
meditation teacher)

Significant distress or discomfort that involves:

Countermeasures (non-prescription medicine) OR

Change in behavior (cancelling plans, decreasing or discontinuing treatment) 
OR

Impairment in at least one domain of functioninga or activities of daily living 
(ADL)b (25%-50% reduction from usual level)
3
Severe

Clinically/medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
(CTCAE)

Health professional/clinical attention needed. Can be outpatient or inpatient.

Significant impairment in at least one domain of functioninga, activities of 
daily livingb or self-carec (>50% reduction in usual level)
4
Very severe

Life-threatening consequences; urgent intervention indicated (CTCAE).

Includes suicidal ideation or attempt

If psychological in nature: requires in-patient hospitalization
5
Death

Death
SERIOUSNESS (requires different reporting process)
Serious

Grades 4 + 5 are serious; Grade 3 may be serious

Results in death

Is life-threatening

Requires hospitalization or prolongs existing stay

Results in congenital anomaly

Causes permanent disability or requires medical/surgical intervention to 
prevent permanent disability or any of the above.
a Domains of functioning = occupational (work), educational (school), social (friendships, 
community), role (parenting, spouse), cognitive (memory, decision-making).
b Activities of Daily Living (ADL) = preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 
c Self care = bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden.
OHRP. (2007). Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to 
Subjects or Others and Adverse Events: Office for Human Research Protections, US 
Department of Health and Human Services.
NCI. (2017). Common Terminology Criteria for Adverse Events (CTCAE) v5.0. National Cancer 
Institute, NIH, U.S. Department of Health and Human Services. 
Linden, M. (2013). How to define, find and classify side effects in psychotherapy: from unwanted 
events to adverse treatment reactions. Clin Psychol Psychother, 20(4), 286-296.
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Appendix C2
LIST OF PREVIOUSLY-REPORTED MEDITATION EFFECTS
(From Lindahl et al 2017 The Varieties of Contemplative Experience, PLOS ONE)
Affective Domain                                    
(13 Categories)
Description
Affective Flattening, Emotional 
Detachment, or Alexithymia
A narrowed or diminished affective range, a lack of affective charge, and/or 
an inability to identify/distinguish emotions.           
Affective Lability
Rapid shifts in mood, mood swings, a increased range of emotions, or 
strong, unwarranted reactions to situations.
Agitation or Irritability
An agitated or irritable mood, possibly accompanied by restlessness, 
distractibility or uneasiness. 
Change in Doubt, Faith, Trust, or 
Commitment
Changes (increase or decrease) in doubt, faith, trust or commitment in 
relation to religious doctrines, practices, goals, community or in relation to 
oneself in any dimension of life, such as self-confidence.     
Crying or Laughing
Crying and laughing, and associated vocalizations.
Depression, Dysphoria, or Grief 
Low, depressed, or sad moods, usually coupled with physical and behavioral 
manifestations that may or may not affect normal functioning.
Empathic or Affiliative Changes 
Increased or decreased empathic connection to other people or to 
environmental stimuli. 
Fear, Anxiety, Panic, or Paranoia
Feelings of fright or distress--with or without an external referent--and their 
corresponding physiological and behavior responses.
Positive Affect
A state of positive or elevated mood or energy level, ranging on a continuum 
from low to high arousal.
Rage, Anger, or Aggression
Feelings of intense displeasure or a retaliatory response, often caused by 
some adverse stimulus provoking an uncomfortable emotion.
Re-experiencing of Traumatic Memories 
or Affect Without Recollection
Either a recollection of some past traumatic event in the subject's life that 
may or may not have been repressed, and which is generally associated 
with strong emotions, or the upwelling of strong emotions without any 
corresponding memory, content, thought or other identifiable stimulus. 
Self-Conscious Emotions
Emotions relating to one's sense of self and identity, as well as the 
awareness of reactions of others to oneself, whether real or imagined.
Suicidality
Affect-driven ideation concerning wanting to die, not wanting to continue with 
life, wishing to no longer being alive, thinking about taking one's own life, or 
thinking about or making specific plans for taking one's own life.
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Cognitive Domain                                  
(10 Categories)   
Description
Change in Executive Functioning 
Either an inability to perform cognitive functions of decision making, 
concentration, and memory that the person used to be able to perform, or an 
enhanced ability in these domains of executive functioning.
Change in Worldview
A shift in ways of thinking about the nature of self or reality, including a 
change in understanding or confusion about the nature of self or reality.
Clarity 
Reports of clarity or lucidity as a mental state, quality of attention, or quality 
of consciousness, in which there is a heightened cognition of relevant stimuli 
and a diminished interference from non-relevant stimuli. 
Delusional, Irrational, or Paranormal 
Beliefs
Holding with conviction and being influenced by one or more beliefs despite 
evidence to the contrary. Ascriptions of significance or meaning that are later 
disregarded or that might seem unusual or concerning to members of the 
practitioner's broader culture or particular subculture. Attributions of 
paranormal agency, origin, or explanation for cognitive experiences.
Disintegration of Conceptual Meaning 
Structures
Percepts arise but are processed without their associated conceptual 
meaning, resulting in an inability to form conceptual representations of the 
perceptual world.
Increased Cognitive Processing 
Primarily a cognitive change in thought amount or speed of cognitive 
processing, though the increase in processing often coincides with a 
decrease in sensory gating that leads to the impression of taking in or 
processing more perceptual information than usual.    
Mental Stillness
An state in which there are few identifiable thoughts, a perceived absence of 
thought, or a poor awareness about the thinking process in general. 
Meta-Cognition
Meta-cognition, or meta-awareness, refers to an explicit knowledge of the 
content of thoughts or the thinking process. Meta-cognition can also entail a 
higher-order cognition of processes in other domains of experience, such 
affective, perceptual, somatic or sense of self.
Scrupulosity 
Obsessive thinking, specifically about moral or religious issues and 
behaviors. 
Vivid Imagery
An experience of intense, vivid and/or clear thoughts or mental images that 
arise involuntarily, or a report of an increased ability to visualize. 
Conative Domain                                     
(3 Categories)
Description
Anhedonia or Avolition
Anhedonia is the inability to experience pleasure in activities previously 
found pleasurable. Avolition is the lack of drive or motivation to pursue goals 
previously valued as meaningful. 
Change in Effort or Striving
The degree or intensity of attempts at pursuing something valued-as-good or 
as a means to a valued end. Effort may be mental, physical, or emotional.
Change in Motivation or Goal
The reasons, drives, and needs behind a practitioner's actions, which 
influence or determine their behavior, as well as their expectations 
concerning a particular behavior. 
Perceptual Domain                                  
(7 Categories)
Description
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Derealization
Surroundings are perceived as strange, unreal, or dreamlike, or perception 
is experienced as mediated by a fog, a lens, or some other filter that results 
in feeling cut off from the world. 
Dissolution of Objects or Phenomena 
The dissolving or complete disappearance of visual objects or the entire 
visual field.
Distortions in Time or Space
An alteration in the subjective experience of spatial boundaries or relations 
and/or temporal causality or sequencing.
Hallucinations, Visions, or Illusions
A hallucination is an experience of a percept that is not externally stimulated, 
is not shared by others, and is not taken to be veridical. When a visual 
percept that is not shared by others is taken to be veridical, it is a vision.  An 
illusion involves a percept that is distorted, changed, or has features added 
to the raw percept. 
Perceptual Hypersensitivity
Unusual or atypical sensitivity to certain frequencies or volumes of sound 
(hyperacusis), to color (hyperchromia), to visual details, to light, to taste, to 
smell, or to embodiment.
Somatosensory Changes
A change in proprioceptive information that affects one's perception of 
relative positions or dimensions of body parts or the body more generally. 
Visual Lights
Experience of a light or lights in field of vision that are vivid but not the result 
of external stimuli. 
Sense of Self Domain                              
(6 Categories)
Description
Change in Self-Other or Self-World 
Boundaries
Expansion beyond or distortions in the typical sense of where the 
boundaries between self and other or self and world are delineated. 
Change in Narrative Self
A report of a change in how the practitioner conceives of himself or herself 
as a person. Or, a change in the content of or their perspective on their story 
or personal identity.
Change in Sense of Embodiment
Feeling of being disembodied, located outside or at a distance from one’s 
body, or located in an unusual location within one's body schema.
Loss of Sense of Agency
A loss of a sense of ownership or sense of control over one's actions.
Loss of Sense of Ownership
A loss of the usual sense of owning one's thoughts, body sensations, 
emotions, and/or memories.
Loss of Sense of Basic Self
A loss of the sense of existing, of being a self, or of having a self.
Social Domain                                          
(5 Categories)
Description
Change in Relationship to Meditation 
Community
Changes in relationship with the meditation community (Sangha), whether 
increasing or decreasing degrees of affiliation with the community of 
teacher(s) and other practitioners.
Increased Sociality
Increased extraversion, social contact, friendships or other behavioral 
manifestations indicating an increased valuing of social engagement. 
Integration Following Retreat or 
Intensive Practice 
A destabilizing transition from intensive formal practice to informal practice, 
daily life, or life circumstances. 
Occupational Impairment
An impaired ability to perform in an occupational environment.
Social Impairment
Behaviors indicative of a change in relationship to social networks or social 
situations that inhibits ordinary or desired functioning or level of 
engagement.
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Somatic Domain                                      
(15 Categories)
Description
Appetitive or Weight Changes
Decreased or increased appetite, weight loss or gain.
Breathing Changes
Altered respiration rates that may manifest as a temporary cessation, or 
speeding up or slowing down of breathing. 
Cardiac Changes
Irregular heartbeat, heart palpitations, or other significant irregularities.
Dizziness or Syncope
Dizziness, vertigo (feeling one is spinning or off-balance), lightheadedness 
(feeling one is about to faint), or syncope (a brief loss of consciousness and 
muscle strength, commonly called fainting, passing out or blacking out).
Fatigue or Weakness
A feeling of exhaustion, fatigue or weakness (general or localized).
Gastrointestinal Distress or Nausea
Gastrointestinal problems including (but not limited to) diarrhea, bloating, 
cramping, nausea and vomiting.
Headaches or Head Pressure
Ache, sharp pain, or pressure in the region of the head or neck.
Involuntary Movements
A motor movement usually under voluntary control that occurs without a 
conscious decision for movement.
Pain
Pain is an unpleasant physical sensation, either diffuse or acute, and lasting 
for variable amounts of time.
Parasomnias 
Nightmares, vivid dreams, sleep paralysis or the alleviation of these 
symptoms. 
Pressure, Tension or Release of 
Pressure, Tension
Bodily pressure or tension, or release of bodily pressure or tension, that can 
vary according to location (general or specific), intensity, or length of time. 
Sexuality-Related Changes
Hypersexuality (very frequent or suddenly increased sexual urges or activity) 
or hyposexuality (notably decreased sexual urges or activity). 
Sleep Changes
Changes in sleep amount, sleep need, or sleep depth.
Somatic Energy
A type of sensation moving throughout the body or throughout a body area 
described with language of vibration, energy, current, or other related 
metaphors.
Thermal Changes
Changes associated with heat or cold, whether a general change in sense of 
body temperature or localized to a specific body area.
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Appendix D
Diabetes Doman Expected Events
Diabetes Domain         
(7 Categories)
Description
Cardiovascular
Angina, congestive heart failure, coronary angioplasty, coronary artery bypass 
surgery, coronary artery disease, dyslipidemia, hyperlipidemia, hypertension, 
myocardial infarction, stroke, transient ischemic attack (TIA)
Eye
Blindness, blurred vision, cataracts, detached retina, diabetic retinopathy, 
glaucoma, macular degeneration, macular edema, retinal laser photocoagulation, 
vitreous hemorrhage
Foot/Extremity
Amputation (not due to trauma), claudication, diabetic neuropathy, non-infected foot 
ulcer, peripheral artery disease, peripheral vascular disease, peripheral neuropathy 
(numbness, tingling or burning in hands or feet)
Glycemic
Hyperglycemia, hyperosmolar hyperglycemic state (hyperosmotic hyperglycemic 
nonketotic state), hypoglycemia
Infections
Cellulitis, coronavirus (e.g. COVID-19), Fournier's gangrene, infected foot ulcer, 
influenza virus (flu), pneumonia, pyelonephritis, sepsis, urinary tract infection, wet 
gangrene, wound infection, and other infections
Renal
Chronic kidney disease, diabetic nephropathy, proteinuria, renal disease, renal 
failure
Other 
Fatty liver disease, obstructive sleep apnea, polydipsia, polyphagia, polyuria, weight 
gain, weight loss, and other expected events and symptoms in diabetes.
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