Adaptation and Pilot Study of Yoga to Reduce Depression in Adolescents
Phase: NA
Conditions: Depression
Sponsor: Brown University

DOCUMENT: 
INFORMED CONSENT AND ASSENT 
 
 
 
OFFICIAL STUDY TITLE: 
TREATMENTS FOR IMPROVING MOOD IN DEPRESSED TEENS  
 (TEEN THRIVE-3) 
R34AT009886 
 
 
 
NCT NUMBER: 
NCT03831360 
 
 
 
DOCUMENT DATE: 
(12/10/2020) 
 
 
 
 
 
 

 
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Clinical Intervention Study 
Protocol  
 
 

 
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TREATMENTS FOR IMPROVING MOOD IN DEPRESSED 
TEENS 
Principal Investigators:   
Lisa Uebelacker, Ph.D., MPI 
Associate Professor, Brown University 
Assistant Director of Psychosocial Research, Butler Hospital 
 
Shirley Yen, Ph.D., MPI 
Adjunct Professor, Brown University 
 
Supported by:  
 
The National Center for Complementary and Integrative Health, R34AT009886 
 
 
 
 
 
 

 
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Tool Revision History 
Version Number: 1.1 
Version Date: 9/14/2018 
Summary of Revisions Made: N/A 
 
Version Number: 1.2 
Version Date: 9/24/2018 
Summary of Revisions Made: specified that Phase 1 focus groups may include as few as one 
adolescent/parent for scheduling or other reasons.  
 
Version Number 1.3 
Version date: 11/14/2018 
Summary of Revisions Made: removed the exclusion criteria that stated that participants may 
not be enrolled in CBT for Phase 1 focus groups. Removed the Psychotherapy Practice Scale-
Patient Depression Care Version from the set of screening questions and added a modified 
version to the demographics page.  
 
Version Number 1.4 
Version date: 12/3/2018 
Summary of Revisions Made: minor modifications to exclusion criteria for Phase 2 and 3;  
changes to assessment instruments used including substitution of MINI for K-SADS; specified 
that the BL2 time point is conducted by phone and will not include QIDS administration; clarified 
timing of phone screen, BL1, BL2, and enrollment; clarified how protocol deviations and quality 
management will be recorded 
Version Number 1.5 
Version date: 1/3/2019 
Summary of Revisions Made: clarifications requested by NCCIH; minor errors corrected 
 
Version Number 1.6 
Version date: 2/4/2019 
Summary of revisions made: added language about identification and reporting of protocol 
deviations 
 
Version Number 1.7 
Version date: 3/27/2019 
Summary of revisions made: changed the total number of participants allowed per class to be 
12; modified inclusion criteria; specified injuries due to yoga should be assessed weekly in 
teens only 
 
Version Number 2.0 
Version date: 7/29/2019 
Summary of revisions made: Specified that class is approximately 45 minutes long; Changed 
the manual that used to guide group CBT; Specified that we will exclude adolescents with a 
history of a manic episode (but not exclude adolescents with a possible history of a hypomanic 
episode); expanded recruitment options; Clarified that we may ask the adolescent screening 
questions by phone prior to talking with the parent; Stated that all participants must meet listed 

 
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requirements for inclusion at the phone screen stage in order to have a Baseline 1 (BL1) visit 
scheduled; Revised the language for how we will discuss homework in the yoga classes; 
Changed the assessment schedule to include two MINI modules (mania/ hypomania, and 
suicidality) at M3, M6, and M9; Specified that PHI may be included in a REDCap database that 
is designated for PHI. 
 
Version Number 2.1. 
Version date: 12/5/2019 
Summary of revisions made: we added a brief assessment of teen treatment arm preference at 
baseline. 
 
Version Number 2.2. 
Version date: 12/18/2019 
We revised inclusion criteria to include, in Phase 3/ study A, participants with QIDS >= 10 and 
with suicide ideation if it is currently being treated.   
 
Version Number 2.3. 
Version date: 2/12/2020 
We revised procedures so that, in Phase 3, in order to be invited for a baseline visit, teens must 
score an 8 (rather than 5) or greater on the PHQ-8 on the telephone screen.    
 
Version Number 2.4.  
Version date: 3/13/2020 
We made provisions for being able to conduct interventions via audio/ videoconferencing should 
we be unable to hold in-person classes due to COVID-19.  
 
Version Number 2.5. 
Version date: 3/20/2020.  
Further clarifications regarding risks and benefits of holding classes via videoconference.  
 
Version Number 2.6. 
Version date: 3/26/2020 
Clarified options for paying participants, and that we would send them REDCap link to be able 
to view a written version of the oral consent for videoconference.  
 
Version Number 3.0. 
Version date: 5/1/2020 
Updated protocol to allow for remote recruitment and video-based baseline visit. 
 
Version Number 3.1. 
Version date: 10/29/2020.  
Clarified inclusion / exclusion criteria for passive vs. active suicide ideation. 
 
Version Number 3.2.  
Version date: 12/10/2020 
Changed follow-up duration to 6 months.   

 
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TABLE OF CONTENTS 
Page 
Clinical Intervention Study Protocol Template ......................................................................... 1 
FULL PROTOCOL TITLE ......................................................................................................... 2 
Tool Revision History ................................................................................................................. 3 
TABLE OF CONTENTS ............................................................................................................. 5 
STUDY TEAM ROSTER........................................................................................................... 8 
PARTICIPATING STUDY SITES ............................................................................................ 8 
PRÉCIS ....................................................................................................................................... 9 
1. STUDY OBJECTIVES ........................................................................................................... 10 
1.1 
Primary Objective .......................................................... Error! Bookmark not defined. 
2. BACKGROUND AND RATIONALE .................................................................................. 11 
2.1 
Background on Condition, Disease, or Other Primary Study Focus ............................ 11 
2.2 
Study Rationale ............................................................................................................. 11 
3. STUDY DESIGN ..................................................................................................................... 13 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS .............................................. 13 
4.1 
Inclusion Criteria .......................................................................................................... 13 
4.2 
Exclusion Criteria ......................................................................................................... 14 
4.3 
Study Enrollment Procedures ....................................................................................... 14 
5. STUDY INTERVENTIONS ................................................................................................ 188 
5.1 
Interventions, Administration, and Duration .............................................................. 188 
5.2 
Handling of Study Interventions ................................................................................... 18 
5.3 
Concomitant Interventions ............................................................................................ 20 
5.3.1 Allowed Interventions ............................................................................................... 20 
5.3.2 Required Interventions .............................................................................................. 20 
5.3.3 Prohibited Interventions ............................................................................................ 20 
5.4 
Adherence Assessment ................................................................................................. 20 
6. STUDY PROCEDURES ........................................................................................................ 21 
6.1 
Schedule of Evaluations ................................................................................................ 21 
6.2 
Description of Evaluations ............................................................................................ 25 
6.2.1 Screening Evaluation ................................................................................................ 25 
6.2.2 Enrollment, Baseline, and/or Randomization ........................................................... 25 

 
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6.2.3 Blinding..................................................................................................................... 27 
6.2.4 Followup Visits ......................................................................................................... 28 
6.2.5 Completion/Final Evaluation .................................................................................... 29 
7. SAFETY ASSESSMENTS ..................................................................................................... 30 
7.1 
Specification of Safety Parameters ............................................................................... 33 
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters .... 34 
7.3 
Adverse Events and Serious Adverse Events ............................................................... 34 
7.4 
Reporting Procedures .................................................................................................... 35 
7.5 
Followup for Adverse Events ....................................................................................... 36 
7.6 
Safety Monitoring ......................................................................................................... 36 
8. INTERVENTION DISCONTINUATION ........................................................................... 36 
9. STATISTICAL CONSIDERATIONS .................................................................................. 36 
9.1 
General Design Issues ................................................................................................... 36 
9.2 
Sample Size and Randomization .................................................................................. 39 
9.3  
Definition of Populations .............................................................................................. 39 
9.4 
Interim Analyses and Stopping Rules ........................................................................... 39 
9.5 
Outcomes ...................................................................................................................... 40 
9.5.1 Primary Outcome ...................................................................................................... 40 
9.5.2 Secondary Outcomes ................................................................................................ 41 
9.6 
Data Analyses ............................................................................................................... 42 
10. DATA COLLECTION AND QUALITY ASSURANCE .................................................. 42 
10.1 
Data Collection Forms .................................................................................................. 43 
10.2 
Data Management ......................................................................................................... 43 
10.3 
Quality Assurance ......................................................................................................... 43 
10.3.1 
Training ................................................................................................................. 43 
10.3.2 
Quality Control Committee................................................................................... 43 
10.3.3 
Metrics .................................................................................................................. 43 
10.3.4 
Protocol Deviations ............................................................................................... 43 
10.3.5 
Monitoring ............................................................................................................ 43 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY ................................................... 44 
11.1 
Institutional Review Board (IRB) Review .................................................................... 44 
11.2 
Informed Consent Forms .............................................................................................. 44 
11.3 
Participant Confidentiality ............................................................................................ 44 
11.4 
Study Discontinuation ................................................................................................... 44 

 
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12. COMMITTEES..................................................................................................................... 45 
13. PUBLICATION OF RESEARCH FINDINGS .................................................................. 45 
14. REFERENCES ...................................................................................................................... 46 
15. SUPPLEMENTS/APPENDICES ........................................................................................ 48 
 

 
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STUDY TEAM ROSTER  
Lisa Uebelacker, Ph.D., MPI 
Associate Professor, Brown University 
Assistant Director of Psychosocial Research, Butler Hospital 
Address: Butler Hospital, 345 Blackstone Blvd., Providence, RI, 02906 
Tel: 401-455-6381; Fax: 401-455-6235; Email: luebelacker@butler.org 
 
Shirley Yen, Ph.D. 
Adjunct Professor, Brown University 
Address: 700 Butler Drive, Providence, RI 02906 
Tel: 401-444-1915; Fax: 401-444-1948; Email: Shirley_Yen_PhD@brown.edu 
 
Jennifer Wolff, Ph.D. 
Assistant Professor (Research), DPHB Brown Medical School 
Staff Psychologist, Rhode Island Hospital and Bradley Hospital 
Address: Rhode Island Hospital, Coro West Building, One Hoppin Street, Suite 204, 
Providence, RI 02903 
Tel: 540.921.7574; Fax: 401.444.8742; E-mail: Jennifer_Wolff@brown.edu 
 
Celeste Caviness Ph.D.  
Project Manager, Butler Hospital 
Address: Butler Hospital, 345 Blackstone Blvd, Providence, RI 02906 
Tel: 401-455-6648, Fax: 401-455-6685; E-mail: ccaviness@butler.org 
PARTICIPATING STUDY SITES 
Butler Hospital: 
Lisa Uebelacker, Ph.D., MPI 
Associate Professor, Brown University 
Assistant Director of Psychosocial Research, Butler Hospital 
Address: Butler Hospital, 345 Blackstone Blvd., Providence, RI, 02906 
Tel: 401-455-6381; Fax: 401-455-6235; Email: luebelacker@butler.org 
 
Brown University: 
Shirley Yen, Ph.D., Adjunct Professor 
Address: 700 Butler Drive, Providence, RI 02906 
Tel: 401-444-1915; Fax: 401-444-1948; Email: Shirley_Yen_PhD@brown.edu 
 
Lifespan: 
Jennifer Wolff, Ph.D. 
Assistant Professor (Research), DPHB Brown Medical School 
Staff Psychologist, Rhode Island Hospital and Bradley Hospital 
Address: Rhode Island Hospital, Coro West Building, One Hoppin Street, Suite 204, 
Providence, RI 02903 
Tel: 540.921.7574; Fax: 401.444.8742; E-mail: Jennifer_Wolff@brown.edu 
 
 

 
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PRÉCIS  
Study Title  
Treatments for improving mood in depressed teens 
 
Objectives  
Our proposed project will have three phases. Specific Aims for each phase include:  
 
Phase 1: Initial Development 
1. 
Conduct separate focus groups with depressed adolescents (n=24) and parents (n=24) to 
ascertain their feedback on ways to make yoga classes an acceptable and feasible 
intervention;  
2. 
Solicit feedback from experts in depression, health, and/or yoga in adolescents;  
3. 
Create a manual, training materials, and fidelity assessment scale for instructors.  
 
Phase 2:  Open Trial 
 
4. 
Pilot the 3 month yoga intervention in a sample of 12 adolescents; 
5. 
Via structured interview, elicit feedback from adolescents, parents, and yoga instructors; 
use the feedback to further refine the yoga manual and other related materials. 
 
Phase 3: Pilot RCT (Study A)  
6. 
Conduct a pilot randomized clinical trial (n = 34) of 3 months of hatha yoga vs. group CBT 
for depression for adolescents aged 13-18 with major depression; we also refer to this as 
Study A.  [Note. There will also be a Study B in which we may enroll up to an additional 20 
adolescents that do not meet Phase 3 (Study A) inclusion criteria due to either low 
depression severity on the QIDS or recent changes in treatment. Study B will run concurrent 
to Phase 3/Study A. Participants will undergo the same procedures as the main Phase 3 
participants. Allowing these individuals to participate will allow us to increase the size of 
the yoga/ CBT classes, potentially making them of more value for all participants.] 
7. 
Assess feasibility, acceptability, and safety of both the yoga intervention and comparison 
group; 
8. 
Assess within-group changes on outcomes. The primary outcome will be adolescent report 
of depression symptom severity at 3 months, assessed by a blind evaluator. Secondary 
outcomes include depression severity at follow-up (9 months), and self-report of 
depression, functional impairment, and anxiety at 3 and 9 months.  
 
Thus, our primary objective for this pilot project is to develop procedures, and manuals, and 
acquire supportive data on feasibility and acceptability that will prepare us to conduct a fully-
powered non-inferiority design trial of hatha yoga vs. group CBT for depression in adolescents. 
 
Design and Outcomes   
In Phase 1, we will conduct focus groups with adolescents with depression, with separate 
but concurrent focus groups for their parents. 
 
In Phase 2, we will conduct an open single-arm pilot trial of our adapted hatha yoga to 
examine feasibility, acceptability, and safety, and to gather additional feedback from adolescents, 
parents, and yoga providers to guide further refinement of the manual. Participants will be 

 
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adolescents with depression. Parents will also be invited to participate in assessments regarding 
their child, although it is not required.  
 
In Phase 3, Study A, we will conduct a pilot RCT of hatha yoga vs. group CBT to assess 
feasibility, acceptability, and safety of these interventions, examine preliminary outcomes of 
depression, functional impairment, and anxiety, as well as engagement of hypothesized 
mechanisms of self-compassion, and metacognitive awareness. Participants will be adolescents 
with depression. Parents will also be invited to participate in assessments regarding their child. 
 
Study B, which will run concurrent to Phase 3, will be for participants who did not meet the 
depression inclusion criteria or had recent changes in therapy or medications that make them 
ineligible for Phase 3. Participants will be randomized to Phase 3 groups of hatha yoga or group 
CBT. Parents will also be invited to participate in assessments regarding their child. 
 
Interventions and Duration  
Yoga classes. The manualized hatha yoga program will begin with a 20-minute initial 
individual session with a yoga teacher, to introduce the participant to yoga and give them a chance 
to privately ask any questions or express any concerns. Subsequently, participants will be asked to 
attend one  class (approximately 45 mins long) per week for 12 weeks. Participants in Phase 2 will 
participate for 3 months. Participants in Phase 3 will participate for 6 or 9 months (12 weeks of 
intervention, 3 or 6 months of follow up). 
 
Phase 3 only - Group CBT. We will provide group CBT for depression.. Participants will 
attend group sessions for 12 weeks. Participants in Phase 3 will participate for 6 or 9 months (12 
weeks of intervention, 3 or 6 months of follow up). 
 
Sample Size and Population  
The proposed project will include up to 24 depressed adolescents and 24 parents who 
participate in focus groups (Phase 1), 12 adolescents in an open trial (Phase 2; also including 12 
parents), 34 human subjects in a randomized controlled trial of yoga vs. group Cognitive Behavioral 
Therapy (CBT) (Phase 3; also including 34 parents), and up to 20 adolescents in Study B (and up to 
20 parents). Participants will be adolescents aged 13-18 years old, regardless of gender. 
 
 

 
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1. STUDY OBJECTIVES 
1.1 Primary Objective 
 
Our primary overall objective for this pilot project is to develop procedures and manuals, 
and acquire supportive data on feasibility and acceptability that will prepare us to conduct a fully-
powered non-inferiority design trial of hatha yoga vs. group CBT for depression in adolescents. 
Our proposed project will have three phases. Specific Aims for each phase include:  
 
Phase 1: Initial Development 
1. 
Conduct separate focus groups with depressed adolescents (n=24) and parents (n=24) to 
ascertain their feedback on ways to make yoga classes an acceptable and feasible 
intervention;  
2. 
Solicit feedback from experts in depression, health, and/or yoga in adolescents;  
3. 
Create a manual, training materials, and fidelity assessment scale for instructors.  
 
Phase 2:  Open Trial 
4. 
Pilot the yoga intervention in a sample of 12 adolescents; 
5. 
Via structured interview, elicit feedback from adolescents, parents, and yoga instructors; 
use the feedback to further refine the yoga manual and other related materials. 
 
Phase 3: Pilot RCT (Study A) 
6. 
Conduct a pilot randomized clinical trial (n = 34) of 3 months of hatha yoga vs. group CBT 
for depression for adolescents aged 13-18 with major depression; we also refer to this as 
Study A.  [Note. There will also be a Study B in which we may enroll up to an additional 20 
adolescents that do not meet Phase 3 (Study A) inclusion criteria due to either low 
depression severity on the QIDS or recent changes in treatment. Study B will run concurrent 
to Phase 3/Study A. Participants will undergo the same procedures as the main Phase 3 
participants. Allowing these individuals to participate will allow us to increase the size of 
the yoga/CBT classes, potentially making them of more value for all participants.] 
7. 
Assess feasibility, acceptability, and safety of both the yoga intervention and comparison 
group; 
8. 
Assess within-group changes on outcomes. The primary outcome will be adolescent report 
of depression symptom severity at 3 months, assessed by a blind evaluator. Secondary 
outcomes include depression severity at follow-up (9 months), and self-report of 
depression, functional impairment, and anxiety at 3 and 9 months.  
2. BACKGROUND AND RATIONALE 
2.1 
Background on Condition, Disease, or Other Primary Study Focus 
Recent reports have shown an alarming increase in prevalence of depression in adolescents, 
particularly girls, as well as increased numbers of untreated depression in adolescents [1]. This is 
true despite improved access to health care from 2000 to 2014 across all socioeconomic groups [2] 
and data supporting more efficacious treatment of depression in adolescents [3]. Thus, testing 
alternative approaches to treating depression in adolescents, including approaches that do not rely 
on the limited pool of child and adolescent mental health providers, is an urgent public health 
priority.  

 
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2.2 
Study Rationale 
Yoga is an ancient Indian system of philosophy and practice [4]. In the U.S., most people 
who practice yoga practice hatha yoga, which involves training the body through breath control, 
physical postures, and meditation in order to promote mental and physical well-being. A meta-
analysis of 12 randomized controlled trials (RCTs) of yoga for depressive symptoms in adults 
reported yoga was significantly better than usual care, relaxation, or aerobic exercise in decreasing 
depressive symptoms [5]. More recent research confirmed these findings [6, 7]. We recently 
conducted an RCT of adjunctive hatha yoga (vs. a health education control) for adults with current 
or recent major depression who were taking an antidepressant and continued to have persistent 
depressive symptoms (n=122) [8]. The intervention period lasted for 10 weeks, and we assessed 
participants for an additional 6 months. Although differences between groups in depression 
symptom severity were not statistically significant at 10 weeks, they were significantly different 
over the 6-month follow-up period, favoring the yoga arm. Thus, even in this difficult-to-treat group 
of adults, we found that hatha yoga had an enduring effect on depressive symptoms.  
 
There are various plausible mechanisms by which yoga may have an impact on depression, 
including self-regulatory mechanisms. On the psychological level, yoga may increase self-
compassion and one’s ability to observe one’s thoughts and feelings as subjective and transient 
internal experiences rather than objective and permanent reality (i.e., meta-cognitive awareness). 
On the biological level, yoga may lead to increased heart rate variability, reflecting an improved 
ability to regulate one’s biological and other responses to stress.  
 
There are fewer studies of hatha yoga in adolescents than in adults, and very few studies of 
the effect of yoga on mood. We were unable to find any studies that rigorously examined yoga in 
adolescents with clinically significant depression symptoms at baseline. Given yoga’s promising 
results in adults, and presumed mediators, we believe that hatha yoga may be a useful and safe 
intervention for depression in adolescents. However, it is necessary to adapt existing hatha yoga 
manuals for use in depressed adolescents. Using the Participatory Action Research framework, we 
will adhere to step-wise guidelines for adapting manualized interventions [9] which include 
conducting separate focus groups with adolescents and parents; soliciting feedback from experts; 
making iterative revisions of an instructor manual, and conducting pilot open and randomized 
controlled trials. We will classify specific modifications (to be informed by focus groups and expert 
feedback) using the system proposed by Stirman [10] to facilitate adaptation by other research 
groups.  
We will then conduct an open trial of hatha yoga for adolescents with depression, followed 
by a pilot randomized clinical trial of hatha yoga vs. group CBT for depression. We chose group CBT 
as this is an empirically supported treatment for depression in adolescents [11], and we plan to 
ultimately conduct an equivalency trial.  In both trials in this project, adolescents will receive the 
active intervention (i.e., weekly classes) for a 12-week period. Twelve weeks was chosen because it 
is sufficient time for improvement in depression symptoms and to administer the comparison 
intervention, group CBT for depression. Adolescents will attend classes once per week as more 
often is likely impractical (although we will discuss this issue in focus groups). Adolescents will be 
asked to complete relevant homework regardless of whether they are in hatha yoga classes or CBT 
classes. Potential risks of both interventions include loss of privacy or breach of confidentiality, 
increased distress due to procedures, and ineffective intervention (i.e., lack of improvement in 
depression symptoms). Potential risks of yoga include mild physical injury.  

 
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3. STUDY DESIGN 
In Phase 1, we will conduct focus groups with 24 adolescents with depression, with 
separate but concurrent focus groups for their parents (n=24). We will use focus group feedback to 
adapt our existing yoga program for use with adolescents. We will also separately solicit feedback 
from experts in depression, health, and/or yoga in adolescents. We will also create accompanying 
training materials and an instructor fidelity assessment scale. Enrollment period for this phase will 
last approximately 4 months.   
 
In Phase 2, we will conduct an open single-arm pilot trial (n=12 adolescents) of our adapted 
hatha yoga to examine feasibility, acceptability, and safety, and to gather additional feedback from 
adolescents, parents, and yoga providers to guide further refinement of the manual. Participants 
will be adolescents with depression who will be in the study for 3 months; they will attend yoga 
classes once per week for all 3 months. Yoga instructors will also invite participants to engage in 
home-based yoga practice. We will also invite parents to participate in assessments regarding their 
child.  Enrollment period for this phase will last approximately 4 months 
 
In Phase 3, we will conduct a pilot RCT of hatha yoga vs. group CBT (study A; n=34 
adolescents) to assess feasibility, acceptability, and safety of these interventions, examine 
preliminary outcomes of depression, functional impairment, and anxiety, as well as engagement of 
hypothesized mechanisms of self-compassion, and metacognitive awareness. Randomization will be 
blocked and stratified by gender. Participants will be adolescents with depression who will receive 
their assigned intervention for 3 months and then also have follow-up assessments for 3 or 6 
months. We will also invite parents to participate in assessments regarding their child. A blind 
evaluator will assess outcomes that do not directly reference which study arm participants are 
enrolled in.  Enrollment period for this phase will last approximately 6 or 9 months. All study 
procedures will occur at Butler Hospital.  
 
Study B, which will run concurrent to Phase 3, will be for participants (n = 20 adolescents 
maximum) who did not meet the depression inclusion criteria or had recent changes in therapy or 
medications that make them ineligible for Phase 3.  Enrollment will be blocked and stratified by 
gender (and be separate from randomization for Study A). Participants will be randomized to Phase 
3 groups of hatha yoga or group CBT for 3 months, and then have follow-up assessments for 3 or  6 
months.  We will also invite parents to participate in assessments regarding their child. 
 
All parts of the study will be conducted at Butler Hospital, with community participants. 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1 
Inclusion Criteria 
Participants must meet all of the relevant inclusion criteria to participate in the study.  
Phase 1 (Focus Group) Inclusion Criteria – Adolescents 
These are designed to be similar to inclusion criteria for Phase 2 and 3, but because 
adolescents will not be participating in the yoga intervention and are only attending a single focus 
group, criteria is more inclusive than Phase 2 and 3 to reduce assessment burden.  
 
a) Adolescents must have elevated depressive symptoms, defined by a score of 8 or higher on 
the PHQ-8, and a “1”or greater on at least one of the following two items: sad mood, or 

 
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anhedonia.  
b) Adolescents must be aged 13-18.  
c) Adolescents must be medically cleared for moderate physical activity by their primary care 
physician.  This criterion will be assessed by adolescent or parents self-report that the 
adolescent has a current (dated in the past year) statement from their pediatrician that the 
adolescent may participate in school or camp programs including physical education.  
d) Adolescents must be able to read and write English sufficient to complete informed consent 
and engage in interventions. 
e) Adolescents aged 13-17 must assent to be in the study, and their parent/legal guardian 
must consent to their participation. Adolescents aged 18 must consent to be in the study. 
f) Able to attend a focus group.  
Phase 2, Phase 3 Study A, and Phase 3 Study B Inclusion Criteria – Adolescents 
Please note, inclusion criteria for Phase 2, Phase 3 Study A, and Phase 3 Study B are 
identical, with the exception that, for Phase 3/Study B, we will not require elevated depressive 
symptoms (a) or stable treatment (b). 
 
a) Adolescents must have elevated depressive symptoms, defined by a score of 10 or higher on 
the Quick Inventory of Depression –Adolescent Version-- Clinician Rating (QIDS-A-CR; [12-
14]), including endorsement of either sad mood or anhedonia on the QIDS. 
b) Other treatment for depression must be stable at baseline. Adolescents do not have to be in 
other treatment for depression, but, if they are, it must be stable with no substantive 
changes for the past 8 weeks. If unexpected changes in treatment occur during the study 
protocol period, participants can remain in the study and this treatment change will be 
captured as data. 
c) Adolescents must be aged 13-18.  
d) Adolescents must be medically cleared for moderate physical activity by their primary care 
physician.  This criterion may be met by a current (dated in the past year) statement from 
their pediatrician that the adolescent may participate in school or camp programs including 
physical education.  
e) Adolescents must be able to read and write English sufficient to complete informed consent 
and engage in interventions. 
f) Adolescents aged 13-17 must assent to be in the study, and their parent/legal guardian 
must consent to their participation. Adolescents aged 18 must consent to be in the study.  
g) Able to attend one of the class times. 
h) Access to a private space in their home for study classes, and a device that will support use 
of the video platform we are using to conduct assessments and classes. 
Parent Inclusion Criteria for all Phases 
a) Parent/legal guardian of an adolescent who is eligible for the study. 
b) Provides informed consent. 
c) Able to read and write English sufficient to complete informed consent and study 
questionnaires. 
4.2 
Exclusion Criteria 
Phase 1 (Focus Group) Exclusion Criteria – Adolescents 
a) Adolescents may not have current suicide ideation or behavior that warrants immediate 
treatment. They may have passive ideation (i.e., thoughts that life is not worth living), but 

 
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may not have active suicide ideation, intent, plan, or an attempt within the previous 6 
months. We will not actively assess this for Phase 1, but we will exclude an adolescent if 
they indicate they have active suicide ideation.  
b) Adolescents cannot currently be engaged in yoga classes, as these are the study 
interventions. 
Phase 2, Phase 3 Study A, and Phase 3 Study B Exclusion Criteria – Adolescents 
Exclusion criteria for Phase 2, Phase 3 Study A, and Phase 3 Study B are identical. 
 
a) QIDS- A-SR may not be higher than a score of 21. This ensures that adolescents are not 
severely depressed. 
b) Adolescents may not meet criteria for the following:  
i.  Autism spectrum disorder (AS) “cannot be ruled out” (via MINI), and symptoms are 
of sufficient severity to interfere with study treatment per clinician judgment; 
ii. Current psychotic disorder 
iii. Lifetime history of a manic episode 
iv. Anorexia or Bulimia in past 3 months 
v. Substance use disorders in past 12 months, and symptoms are of sufficient severity 
to interfere with study treatment per clinician judgment 
 These will be assessed with the Mini-International Neuropsychiatric Interview (MINI).  
c) Adolescents may not have current untreated active suicide ideation or behavior. They may 
not have had a suicide attempt in the previous 6 months. They may not have suicide 
ideation that is so severe that the study clinician judges it will interfere with study 
participation (e.g., if the clinician judges they need a higher level of treatment now or 
potentially very soon). This means that adolescents with active suicide ideation may be 
included if they are receiving stable mental health services (e.g., therapy, counseling) and 
suicidal ideation is known to the mental health provider. Adolescents may be included if 
they have passive ideation (i.e., thoughts that life is not worth living) but are not in active 
treatment.  
d) Adolescents cannot currently be engaged in yoga classes, as this is the study intervention. 
e) Adolescents cannot be pregnant as yoga should be modified for pregnancy [15]. 
Parent Exclusion Criteria for all Phases 
None. Please see parent inclusion criteria above.  
4.3 
Study Enrollment Procedures  
Recruitment and Screening 
 
For all phases, participants will be recruited from the community and through outpatient 
primary care and specialty mental health clinics. We will recruit from the community using social 
media, schools, and flyers in local businesses that cater to adolescents. We may include 
advertisements on city buses that take teens to school. We will recruit on Facebook, Instagram, 
Craig’s List, and other social media sites if needed. We will post study information on a study 
website hosted by Butler Hospital; social media ads and posters will direct participants to the 
Butler website, where participants can request contact from the study staff. When an adolescent (or 
parent) calls or indicates interest, a research assistant will describe the study to the adolescent and 
parent by telephone.  If they are both interested in having the adolescent participate, the RA will 
assess some inclusion criteria by phone (i.e, a phone screen).   

 
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For Phase 1, the RA will assess all inclusion criteria by phone once they have verbal 
agreement from the adolescent and the parent.  RAs will tell the adolescent and parent what types 
of questions will be asked as part of the screening process, and then document that both the 
adolescent and parent have agreed to being screened by phone prior to beginning the actual 
screening process.  The phone screen will be used to determine eligibility; there will be no other 
eligibility determination.  The RA will administer the PHQ-8, will inquire about age, engagement in 
yoga, ability to attend a focus group, and medical clearance. If the adolescent is eligible, the RA will 
schedule the adolescent and parent to attend focus groups that will occur within the next 30 days.  
 
 
 
For Phase 2, Phase 3 Study A, and Phase 3 Study B, the RA will describe study procedures to 
the adolescent, including what questions will be asked as part of the screening process on the 
phone. The adolescent will be made aware that the written consent of the adolescent’s parent is 
needed to proceed in the study itself, if the adolescent is 17 years old or younger. RAs will seek 
verbal agreement from the adolescent and document that agreement occurred prior to beginning 
the actual screening process. RAs will then assess the following inclusion criteria by phone after 
obtaining verbal agreement from the adolescent: 
 
a) Adolescents must be able to read and write English sufficient to complete informed consent 
and engage in interventions. 
b) Adolescents must be aged 13-18.  
c) Able to attend one of the class times.  
d) Adolescents cannot currently be engaged in yoga classes. 
e) Other depression treatment is stable  
f) Access to a private space in their home for study classes, and a device that will support use of 
the video platform we are using to conduct  assessments and classes. 
 
In addition, by phone, the RA will verify that: 
 
a) The adolescent is currently experiencing some degree of depression symptoms (i.e., PHQ-8 
>=8). 
b) They are able to participate in physical activity, and either have a form signed by their 
pediatrician or are able to get one.  
 
 
If adolescents appear potentially eligible by phone, the RA will:  
a) Conduct a verbal consent (with parent if teen is 17 or younger) to send an email link and 
conduct a Zoom video meeting;  
b)  Schedule that meeting to obtain informed consent by parent (if aged 17 or younger) and 
assent from adolescent, or informed consent from 18 year old participant.  
c) Email links to the Zoom meeting, electronic informed consent, and electronic assent for teen 
Informed Consent Procedures 
 
Research assistants will perform this process. An electronic-signed consent form will be 
obtained from each participant using procedures outlined by the Butler Hospital IRB.  Via video call 
and review of an electronic version of consent/ assent forms, all participants and parents will be 
fully informed of the purposes and procedures of the study. On the consent form and orally, 
participants will be given information about: who is sponsoring the study; a description of study 
procedures, including the process of randomization and the nature of the assessments; risks and 
inconveniences; benefits; compensation for study participation; alternative treatment options; 

 
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confidentiality, including the limits to confidentiality; the voluntary nature of their participation; 
and who to contact should they have questions. After making sure that the participant and parent 
have a full understanding of the nature and purposes of the study, the research assistant will obtain 
assent (consent if 18) from the adolescent and informed consent from the parent. For adolescents 
aged 17 and under, the parent will e-sign two consent forms: one for the adolescent to participate 
(required), and one for the parent to participate in assessments themselves (not required for the 
adolescent to participate).  Adolescents aged 18 may also chose to have their parents participate by 
completing assessments, but it is not required. Assent/consent will be documented through the 
individual’s e-signature on the respective forms, which will be kept in the CNE instance of REDCap. 
Participants and parents will be invited to print a copy of the assent/consent form to keep. 
 
 
In Phase 1, we will begin the focus group immediately after conducting informed consent.  
 
 
In Phase 2 and Phase 3, at the BL video-based visit, we will confirm inclusion criteria 
previously assessed via phone screen and assess the remainder of the inclusion criteria. Parents or 
adolescents aged 18 will next be asked to sign a release of information form that will allow us to 
contact their pediatrician by fax, describe the study, and request medical clearance to participate in 
mild-moderate physical activity. As an alternative, we will accept a form from their pediatrician in 
the prior year that states the adolescent may participate in school or camp programs including 
physical education.  If the adolescent has a mental health provider, we will ask for a release of 
information to contact their MH provider to provide information about the study. Doing so 
establishes a relationship should we need to contact them in the future due to significant clinical 
deterioration or the development of active suicide ideation. Adolescents cannot begin classes until 
we gain medical clearance.  
Enrollment and Randomization 
 
 In Phase 1, participants are considered enrolled immediately after signing the consent 
form.    
 
 
In Phase 2, once we have medical clearance to participate in physical activity from a 
participant, and talk with the participant to confirm their interest, they are considered “enrolled.”  
Enrollment may occur at the BL visit or at a separate BL2 phone call (if there is a need to request 
and wait for medical clearance). BL2 must occur within 14 days of BL1.  
 
 
In Phase 2, adolescents are invited to attend classes within a week after enrollment.   
 
 
Randomization occurs in Phase 3 only. Randomization will occur at a BL2 phone call. 
Participants are considered enrolled at BL2 after randomization. Adolescents invited to begin the 
study intervention within a week after enrollment.    
Documentation of Reasons for Ineligibility 
 
All participants who express interest in the study (i.e., make contact with us regarding the 
study) will be tracked in a separate database along with the status of their participation. Any 
participant who is screened by phone for any aspect of the study including Phase 2, Phase 3 Study 
A, and Phase 3 Study B (even if only one inclusion criterion is assessed before the participant is 
determined not eligible) will have a study record documenting which inclusion criteria were 
assessed and the outcome of that assessment (i.e., as part of a study log). The study record is linked 
to the participant’s name and other personal identifiers only by the study ID number. Once study 

 
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status is determined (i.e., determination that a person is not eligible and the reason), we will not 
retain the names of potential participants if they have not signed a consent form.   
5. STUDY INTERVENTIONS  
5.1 
Interventions, Administration, and Duration  
Yoga classes are administered to a group of participants. Participants attend classes once 
per week; they will also be asked to practice yoga at home. Classes will take place in a room on the 
Butler Hospital campus; they are planned to be 45 minutes long. Registered yoga teachers will 
deliver the intervention. Potential risks include loss of privacy or breach of confidentiality, 
increased distress due to procedures, ineffective intervention (i.e., lack of improvement in 
depression symptoms), and mild physical injury. 
Group CBT is administered to a group of participants. Participants attend groups once per 
week; they will also be given homework assignments. Classes will take place in a room on the 
Butler Hospital campus. Therapists will have a master’s degree or Ph.D. in psychology or a related 
field (e.g., social work). Potential risks include loss of privacy or breach of confidentiality, increased 
distress due to procedures, and ineffective intervention (i.e., lack of improvement in depression 
symptoms). 
COVID Modifications 
In the event we are unable to hold in-person classes (i.e., due to a major public health 
emergency), we will hold classes via videoconference. This would be through the use of HIPAA-
compliant videoconference service.  
We will send information about accessing the videoconference to participants via email, 
according to preferences for method of contact indicated by participants/ parents/guardians 
during the baseline consent process.   
For participants who began study prior to COVID modifications (and therefore had an 
opportunity to switch to remote participation after consenting to and participating in in-person 
participation):  Prior to sending out video links and holding video-based classes, we will conduct 
telephone consent / assent for remote participation with parents and teens, and document that 
they understand risks and benefits of remote participation, and consent/ assent to participate. We 
will use an IRB-approved script to do this. Any participants who have already consented to 
receiving REDCap links via email will also be asked if they would like to receive a REDCap link that 
will bring them to a written version of that oral consent script, so that they may follow along with 
the consent.    
Participants who begin study after COVID modifications will be consented in all processes at 
the baseline visit. These participants will have study materials (mat and blocks for yoga, or CBT 
workbook) mailed or dropped off at their house.  In addition, these participants will be required to 
have their cameras on while participating in study interventions.  
 
 
5.2 
Handling of Study Interventions  
Yoga Intervention 
Yoga classes. The manualized hatha yoga program will begin with a 30-minute initial 

 
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individual session with a yoga teacher, to introduce the participant to yoga and give them a chance 
to privately ask any questions or express any concerns. In this individual session, teachers will 
focus on how to practice yoga in a way that is physically safer, and review signs that a participant 
should alter or back out of a pose.  
 
Subsequently, participants will be asked to attend one 45 minute class per week for 12 
weeks. Each class will consist of: introduction of a theme; pranayama (breathing practices); 
standing postures (asanas); floor postures; inversions; guided savasana (relaxation); and home 
practice assignments. Classes will emphasize breath-linked movement and moderate physical 
activity. Class size will range between 1 and 12 participants.  
 
Yoga Home Practice. Home practice will be essential for increasing yoga “dosage.” When 
participants first start class, we will give them a yoga mat to take home. In each class, the yoga 
instructor will review specific practices and recommend that participants try those practices at 
home. The practices will always be ones that carry with it minimal risk of injury, and instructors 
will go over safe practice in class. Sample practices that may be introduced for homework include: 
3-part breath, a cat-cow-child sequence, and a half sun salutation. Participants may continue in the 
study regardless of whether they practice at home.  
 
Yoga Instructors. The Yoga Alliance is a professional organization which sets standards for 
yoga teacher training. One can be a Registered Yoga Teacher (RYT) at the 200- or 500-hour level. 
Experienced Registered Yoga Teachers (E-RYT) at the 500-hour level have at least 4 years of 
experience and 2000 hours teaching, and are qualified to train teachers and provide continuing 
education. We will require that all study yoga teachers be RYTs and will have previous experience 
working with adolescents. Teachers will also have study-specific training on research methods, 
working with depressed adolescents, and the yoga manual.  They will meet approximately monthly 
for supervision.  There will be at least 2 trained yoga teachers. Yoga supervisors will also review 
audio recordings of classes to assess instructor adherence.  
 
Yoga instructor Manual Fidelity.  All classes will be audio recorded. After training, Dr. 
Uebelacker and Ms. Conti will rate 10% of all classes for adherence to the yoga manual. Similar to 
previous research, they will use an adherence scale which consists of a) a checklist of required 
practices or types of practices as specified in the manual; and b) ratings (satisfactory, 
unsatisfactory) on core principles as detailed in the manual. If an instructor leads a class that fall 
below 80% adherence on either scale, it may be grounds for re-training. However, because this is a 
treatment development study, this may also be an indicator that the manual itself needs to be 
clarified. Dr. Uebelacker will consult with lead yoga instructor Ms. Conti on this possibility, and 
make small clarifications to the manual as needed. Any larger changes deemed necessary would 
occur after the open trial or pilot RCT (unless they are immediately necessary for participant 
safety). 

 
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Group CBT 
Groups. We will adapt the Stress and Your Mood manual and workbook to guide group CBT 
for depression [16].  This manual focuses on core CBT skills, including behavioral activation, 
communication and social skills, problem-solving, and cognitive restructuring. They will be given 
optional assignments to complete at home.  Prior to the start of class, participants will have a 30-
minute individual meeting with one of the group therapists to orient them to the group. Class size 
will range between 1 and 12 participants. There will be at least 2 trained therapists for this group.  
Homework.  Participants will be given optional assignments to complete at home. 
Therapists.  Therapists will have a master’s degree or Ph.D. in psychology or a related field 
(e.g., social work), and will have previous experience with CBT and with adolescents. The therapist 
will have study specific-training and will meet approximately monthly for supervision. Dr. 
Uebelacker will review audio recordings to assess therapist adherence to the study manual.  
CBT Therapist Manual Fidelity. Procedures will mirror procedures used for yoga teachers. 
After training, Dr. Uebelacker or a qualified co-Investigator will rate 10% of all groups for 
adherence to the therapist manual. They will use a checklist to assess fidelity to the manual for each 
class, and a separate scale to assess adherence to core principles of CBT. Any classes that fall below 
80% adherence will be grounds for re-training. 
 
5.3 
Concomitant Interventions  
5.3.1 Allowed Interventions 
Once a participant is enrolled in the study, participants will not be excluded for any 
concomitant intervention. For example, if a participant begins outside yoga classes while they are in 
the study, we will record that information, but not require that they discontinue study 
interventions.  If a participant changes their dose of antidepressant medication, or outside therapy, 
we will record that information, but not require that they discontinue study participation.  
5.3.2 Required Interventions 
None.  
5.3.3 Prohibited Interventions 
None.  
 
5.4 
Adherence Assessment  
 
Yoga Participant Adherence.  To be considered adherent, a participant must attend 8/12 
classes and engage in  home practice at least 2 times per week for 8/12 weeks (as assessed via self-
report).  
 
CBT Participant Adherence.  Participant adherence is defined as number of groups 
attended; we define “satisfactory” adherence as attending 8/12 groups. 
 
 

 
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6. STUDY PROCEDURES  
6.1 
Schedule of Evaluations 
Table 1. Schedule of Evaluations, Phase 1.  
 
Assessment 
Phone Screening: 
(Day-30 to Day-1) 
Baseline, Enrollment,  
Visit 1 (Day 0) 
Inclusion/Exclusion 
X 
 
PHQ-8 
X 
 
Informed Consent Form 
 
X 
Demographics and Psychotherapy Practice 
Scale-Patient Depression Care Version 
 
X 
Payment – Adolescent 
 
$35 
Payment – Parent 
 
$35 
 

 
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Table 2, Schedule of Evaluations, Phase 2 and Phase 3.  
Assessment 
Type of 
Assessment 
Phone 
Screening: 
(Up to 30 days 
before BL1) 
Baseline 1, 
Visit 1 
 
Baseline 2; must 
occur with 14 
days of BL1 
After 
initial 
class 
Weekly M1, 
M2, M3 
M1 
visit 
M2 
visit 
M3 
visit 
M6 visit 
(Phase 3 
only) 
M9 visit 
(Phase 3 
only)** 
Inclusion/Exclusion  (A) 
Interview, pre-
randomize. 
X 
X 
 
 
 
 
 
 
 
 
Informed Consent Form (A/P) 
Pre-
randomize. 
 
X 
 
 
 
 
 
 
 
 
Enrollment – Phase 2 
Interview,  
non-blind RA 
 
X 
 
X 
 
 
 
 
 
 
 
Enrollment and Randomization – 
Phase 3 
Interview,  
non-blind RA 
 
 
X 
 
 
 
 
 
 
 
CEQ (A) 
Self-report, 
non-blind DB 
 
 
 
X 
 
 
 
 
 
 
CSQ-8 (A/P) 
Self-report, 
non-blind DB 
 
 
  
 
 
 
 
X 
 
 
Qualitative Interview (A/P) 
Interview, 
non-blind RA 
 
 
 
 
 
 
 
X 
 
 
Homework Questionnaire (A) 
Self-report, 
non-blind DB 
 
 
 
 
X 
 
 
 
X 
X 
Injuries due to yoga (A) 
Self-report, 
non-blind DB 
 
 
 
 
X 
 
 
 
 
 
SAFTEE (A/P) 
Interview, 
non-blind RA 
 
 
 
 
 
 
 
X 
 
 
Pregnancy (A)  
Interview, 
non-blind RA 
 
X 
 
 
 
X 
X 
X 
 
 
Other Adverse Events 
Interview, 
non-blind RA 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
QIDS-A-CR (A/P) 
Interview, 
blind RA 
 
X 
 
 
 
X 
X 
X 
X 
X 
BDI (A/P) 
Self-report, 
blind DB 
 
X 
 
 
 
 
 
X 
X 
X 
CIS (A/P) 
Self-report, 
blind DB 
 
X 
 
 
 
 
 
X 
X 
X 

 
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Assessment 
Type of 
Assessment 
Phone 
Screening: 
(Up to 30 days 
before BL1) 
Baseline 1, 
Visit 1 
 
Baseline 2; must 
occur with 14 
days of BL1 
After 
initial 
class 
Weekly M1, 
M2, M3 
M1 
visit 
M2 
visit 
M3 
visit 
M6 visit 
(Phase 3 
only) 
M9 visit 
(Phase 3 
only)** 
SCARED (A/P) 
Self-report, 
blind DB 
 
X 
 
 
 
 
 
X 
X 
X 
TMS (A) 
Self-report, 
blind DB 
 
X 
 
 
 
 
 
X 
 
 
SCS (A) 
Self-report, 
blind DB 
 
X 
 
 
 
 
 
X 
 
 
Yoga Practice (IPAQ format) (A) 
Interview, 
non-blind RA 
 
X 
 
 
 
X 
X 
X 
X 
X 
TRAQ (A/P) 
Interview, 
blind RA 
 
X 
 
 
 
 
 
X 
X 
X 
CASA (A/P) 
Interview, 
blind RA 
 
X 
 
 
 
 
 
X 
X 
X 
Psychotherapy Practice Scale – Pt 
Depression Care Version (A) 
Self-report, 
blind DB 
 
X 
 
 
 
 
 
 
 
 
PROMIS Sleep disturbance scale 
(A) 
Self-report, 
blind DB 
 
X 
 
 
 
 
 
X 
 
 
Demographics (A/P) 
Self-report, 
blind DB 
 
X 
 
 
 
 
 
 
 
 
MINI (A/P)  
Interview,  
pre-randomiz. 
 
X 
 
 
 
 
 
 
 
 
MINI Mania/hypomania and 
Suicidality Modules (A) 
Interview, 
blind RA 
 
 
 
 
 
 
 
X 
X 
X 
PHQ-8 (A) 
Interview, pre-
randomiz. 
X 
 
 
 
 
 
 
 
 
 
Teen treatment arm preference (A) 
Self-report, 
blind DB 
 
X 
 
 
 
 
 
 
 
 
Perceived Cohesion Scale (A) 
Self-report, 
blind DB 
 
 
 
X 
 
 
 
X 
 
 
Payment – Adolescent 
 
 
$30 
 
 
 
$20 
$20 
$30 
$40 
$50 

 
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Assessment 
Type of 
Assessment 
Phone 
Screening: 
(Up to 30 days 
before BL1) 
Baseline 1, 
Visit 1 
 
Baseline 2; must 
occur with 14 
days of BL1 
After 
initial 
class 
Weekly M1, 
M2, M3 
M1 
visit 
M2 
visit 
M3 
visit 
M6 visit 
(Phase 3 
only) 
M9 visit 
(Phase 3 
only)** 
Payment – Parent 
 
 
$30 
 
 
 
$20 
$20 
$30 
$40 
$50 
Abbreviations: time points: M1, M2, M3 = months 1, 2, and 3, respectively; M6*, M9* = follow-up assessments at months 6 and 9, RCT only. 
Assessee: A = adolescent; P = parent; A/P = both.  RA = research assistant; DB = database. 
** M9 visit only included for participants who signed a consent form version dated 12/1/2020 or earlier. 

 
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6.2 
Description of Evaluations  
Assessments will be administered by research assistants (RAs) trained in procedures to ensure 
confidentiality and proper management of research data. Adolescents and parents will be assessed 
separately; discrepancies in interview-based measures (e.g., MINI) will be resolved via consultation with 
Dr. Uebelacker or Yen or a qualified co-I prior to the final eligibility determination. 
6.2.1 Phone Screen 
Consenting Procedure 
All phases will have a) agreement from adolescent to conduct screening by phone and b) informed 
consent from adolescent and parent/legal guardian (if adolescent is 17 years old or younger) at the first 
in-person visit.  
For information about agreement to screening, please see section 4.3 Study Enrollment 
Procedures.  
Screening 
For Phase 1, the telephone screen must be conducted within 30 days prior to the scheduled focus 
group.  
For Phases 2 and 3, because all inclusion criteria are verified or re-verified at BL1 (with the 
possible exception of medical clearance); the telephone screen may be conducted as many as 30 days 
prior to BL1. 
Please see section 4.3 for information about what will be assessed on the telephone screen.  
6.2.2a Baseline – Phase 1 (Focus groups) 
Consenting Procedure – Phase 1 
Written informed consent will be obtained at the baseline visit.  
Please see section 4.3 for more information about the consent (and assent) procedures. 
Dr. Caviness (or Dr. Uebelacker, in her absence) will inspect BL documents (consent forms, release 
of information) for completeness within a week after they are signed.  Documents will be stored in a 
locked file cabinet.  
Screening and Enrollment – Phase 1 
In Phase 1, there is no further screening at the Baseline visit. Participants are considered enrolled 
once they sign the informed consent form.  
Assessments – Phase 1 
We will conduct focus groups with adolescents, composed of approximately 6 adolescents each, 
although the size will vary depending on scheduling. It is possible that some “focus groups” will consist of 
only one adolescent or one parent, due to scheduling or other reasons; questions for this 1:1 interview 
will be the same as focus group questions. We will invite parents to attend a focus group that occurs at the 
same time as the adolescent group. After participants sign informed consent/assent, we will collect 
demographic information and Psychotherapy Practice Scale-Patient Depression Care Version via a self-
report questionnaire. We will then present information about yoga classes and general study design.  We 
will ask participants for feedback on each of these aspects of the study, with a particular focus on tailoring 
that may be needed to increase feasibility, acceptability, safety, and efficacy for treating depression in this 
population.  Each focus group will be no longer than 2 hours, including the consent process at the 

 
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beginning. All groups will be audio recorded and transcribed. Transcriptions will not include names or 
other personal identifiers. Both adolescents and parents will be paid $35 for their participation.  
6.2.2b Baseline 1 (B1) – Phases 2 and 3 
Consenting Procedure – Phases 2 and 3 
Written informed consent will be obtained at the first baseline visit via e-signature (BL1).  
Please see section 4.3 for more information about the consent (and assent) procedures. 
Dr. Caviness (or Dr. Uebelacker, in her absence) will inspect BL documents (consent forms, release 
of information) for completeness within a week after they are signed.  Documents will be stored on 
REDCap.  
Screening – Phases 2 and 3 
 
After informed consent/assent is complete, RAs will administer the following to ascertain 
inclusion criteria during BL1:  
 
 
QIDS-A-CR – Adolescent (depression symptom severity, suicide ideation)  
 
MINI– Adolescent and Parent (psychiatric disorders) 
 
TRAQ – Adolescent and Parent (depression treatment) 
 
CASA – Adolescent and Parent (depression treatment) 
 
Question pertaining to pregnancy – Adolescent (possibility of pregnancy)  
 
RAs will also ask for proof of medical clearance for physical activity. As an alternative, we will 
accept a form from their pediatrician in the prior year that states the adolescent may participate in school 
or camp programs including physical education. If participants meet all eligibility criteria and are able to 
provide medical clearance for physical activity at their BL1 visit, we will then conduct the remainder of 
the BL1 assessments. 
  
 
For participants who meet all other eligibility criteria, but for whom we need to request medical 
clearance to participate in physical activity from their physician, we will also conduct the remainder of 
the BL1. (We will then request medical clearance from their physician immediately following this visit). 
 
For participants who do not meet eligibility criteria, we will inform adolescent and parent without 
stating specific reason for exclusion, to protect the confidentiality of the adolescent. We will provide 
referrals to the community upon request. 
Baseline Assessments – Phases 2 and 3 
Remaining Baseline1 assessments include:  
 
BDI 
 
CIS 
 
SCARED 
 
TMS 
 
SCS 
 
Promis – Sleep 
 
Yoga Practice (IPAQ format) 
 
Demographics 
 
Psychotherapy Practice Scale 
 
Teen treatment arm preference 

 
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Enrollment – Phase 2 
If participants meet all eligibility criteria and are able to provide proof of medical clearance for 
physical activity at their BL1 visit, they are considered enrolled at their BL1 visit.  BL1 visit date is 
recorded as the enrollment date.  Participants for whom we need to request medical clearance for 
physical activity will need to have a second Baseline 2 contact (phone call) scheduled once we have 
obtained the medical clearance.  BL2 must occur within 14 days of BL1. They are considered enrolled at 
BL2.  
Enrollment and Randomization – Phase 3 
Randomization occurs in Phase 3 only. Allowable window between BL1 and randomization (BL2 
timepoint) is 14 days. Participants are considered enrolled at BL2 after randomization. The participant is 
invited to begin the study intervention within 1 week of randomization.  
Payment – Phases 2 and 3 
 
Payment to adolescents for completion of this visit is $30. Payment to parents for completion of 
this visit is $30.  
6.2.3 Blinding – Phase 3 
Blinding will occur in Phase 3 only. We propose to have one blinded PI and one blinded RA on this 
project. Dr. Uebelacker will be the non-blind PI and will primarily be responsible for supervision of the 
interventionists and ensuring therapist/yoga instructor adherence. Dr. Yen will be the blind PI and will be 
primarily responsible for the supervision of the assessors (including rating ambiguous data on outcome 
measures), and monitoring retention of study participants in aggregate, not by study arm. Dr. Brick, the 
study statistician, will be blind to group assignment (and will have no contact with participants.)  When 
there is a question about whether a participant meets inclusion criteria, Dr. Yen will make a decision 
about inclusion. Dr. Uebelacker and non-blind RA will meet separately to discuss intervention-specific 
concerns (e.g., need to cancel class due to lack of participants). Co-I Dr. Wolff will also assist with 
supervising assessors, and will be blind to treatment group. Project Manager Dr. Caviness will not be 
blind.  
 
To ensure that blindness will be maintained, we will have two separate REDCap 
modules/databases. One will contain study participant data that does not indicate participant 
randomized assignment; the other will have intervention-specific data (e.g., dates of sessions attended, 
yoga homework) that only the non-blind PI and RA will have access to.  
 
In this study, we conduct assessments with both the adolescent and parent, typically at the same 
time. Both RAs are blind to treatment group at baseline, as it has not yet been assigned. The non-blind RA 
will conduct the randomization. For follow-up assessments, we have detailed in Table 2 above whether 
the blind or non-blind RA will conduct a particular assessment.  
 
In reporting adverse events to the Independent Monitoring Committee, determination of “causal 
relationship” will be made by the non-blind PI only, as it may require knowledge of which intervention 
arm the participant is in. The standard Adverse Events Reporting Form of our IRB does not ask for 
intervention arm; thus risk of un-blinding from AE reporting is minimal.  
 
Either PI can conduct suicide or other risk assessments. If the blind PI is conducting a risk 
assessment, she will remind the participant not to reveal the intervention arm. In the unlikely event that a 
risk assessment is needed during class and the blind PI needs to conduct the risk assessment, the non-
blind RA will bring the participant to a neutral location for assessment.  
 
The non-blind PI will meet with yoga instructors and CBT therapists for supervision. The 

 
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instructor/ therapist adherence ratings will be conducted by the non-blind PI and RA. 
 
We will keep a record of any instances of un-blinding. This record will be used to improve 
procedures for a larger clinical trial. After all data are collected and the database is locked, the blind PI 
may be un-blinded so as to contribute to data interpretation.  
 
Participants and parents cannot be blind to study intervention. However, we will present both 
interventions (CBT or yoga) with equipoise to all participants in written materials and orally.  
6.2.4 Follow-up Visits – Phases 2 and 3 
For the purposes of targeting dates for an assessment, we will consider each month = 28 days (4 
weeks exactly). For all follow-up assessments, research staff will make every effort to conduct the 
assessment within one week before or one week after the exact due date of the assessment. However, 
because all data can be analyzed with modern statistical methods regardless of whether it was collected 
inside that window, RAs will still collect data if possible even if it is later than that two-week window. We 
will record optimum date for the assessment (e.g., Enrollment + 84 days for M3 assessment) as well as the 
actual date of the assessment.  
 
If it is not possible to conduct study follow-up assessments in person, they will be conducted by 
telephone and via REDCap survey (For self-report questionnaires).  
Participants will have the option of being paid in one of three ways for assessments conducted by 
phone:  
a. We can hold the cash for them until a date when study staff may meet them in person to give 
them the cash.  
b. If participants have signed consent to allow emails, we can send them an electronic Amazon 
gift card 
c. We can send participants a check by mail.  
 
Phase 2 and 3 Visits:  
 
Weekly for 12 weeks 
o Study classes/groups 
o Homework Questionnaire 
o Injuries due to yoga 
o CEQ;  
o Perceived Cohesion Scale (after initial class only) 
o Any other AEs reported to RAs 
 
 
Month 1 
o Pregnancy question 
o Any other AEs reported to RAs 
o QIDS 
o Yoga Practice (IPAQ format) 
o Payment: adolescent - $20; parent - $20 
 
 
Month 2 
o Pregnancy question 
o Any other AEs reported to RAs 
o QIDS 
o Yoga Practice (IPAQ format) 
o Payment: adolescent - $20; parent - $20 
 

 
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 
Month 3 (Final evaluation for Phase 2) 
o CSQ-8 
o Qualitative interview 
o SAFTEE 
o Pregnancy question 
o Any other AEs reported to RAs 
o MINI – Mania/hypomania module and Suicidality module 
o QIDS 
o BDI 
o CIS 
o SCARED 
o TMS 
o SCS 
o PROMIS-Sleep 
o Yoga Practice (IPAQ format) 
o TRAQ 
o CASA 
o Perceived Cohesion Scale 
o Payment: adolescent - $30; parent - $30  
 
Phase 3 Visits Only: 
 
Month 6 
o Homework questionnaire 
o Any other AEs reported to RAs 
o QIDS 
o BDI 
o CIS 
o SCARED 
o Yoga Practice (IPAQ format) 
o TRAQ 
o MINI – Mania/hypomania module and Suicidality module 
o CASA 
o Payment: adolescent - $40; parent - $40 
o  
 
Month 9 (Final evaluation for Phase 3) 
o Homework questionnaire 
o Any other AEs reported to RAs 
o QIDS 
o BDI 
o CIS 
o SCARED 
o Yoga Practice (IPAQ format) 
o TRAQ 
o MINI – Mania/hypomania module and Suicidality module 
o CASA 
o Payment: adolescent - $50; parent - $50 
NOTE: M9 visit only included for participants who signed a consent form version dated 12/1/2020 or 
earlier. 
6.2.5 Completion/Final Evaluation – Phases 2 and 3 
Even if adolescents drop out of study treatment, we will attempt to collect data at all assessment 

 
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points if adolescents and parents agree to it.   
7. SAFETY ASSESSMENTS  
For yoga, the only expected adverse event is:  
 
Physical injury (mild). This includes mild aches or pain during or shortly after yoga 
classes. 
 
For group CBT, there are no expected adverse events.   
 
Risks of study participation include:  
 
Coercion 
 
Increased distress due to intervention or assessment procedures 
 
Ineffective intervention.  
 
Loss of privacy or breach of confidentiality 
 
 
 
Risks and measures to reduce those risks are detailed below. 
 
 
Potential coercion.  It is possible that individuals (adolescents, parents) may feel coerced into 
participating. This risk is a serious one but we believe that it is highly unlikely given informed consent 
processes and the ease with which one may withdraw from the study. We will follow standard procedures 
for obtaining informed consent.  Study staff will fully explain the study procedures, risks, benefits, and 
alternatives to all potential participants and their parents. Parents and adolescents will be aware that 
they may refuse to participate or drop out of the study at any time without any negative repercussions 
from study staff, health care providers, or affiliated institutions. 
 
 
 
Confidentiality and loss of privacy.  Study personnel will be collecting considerable information 
about the study participants.  This may create some distress and could cause social and psychological risk 
if released inappropriately. This risk is a serious one but we believe that it is highly unlikely. 
 
 
 
All information will be collected and handled by research staff trained to deal appropriately with 
sensitive clinical issues. All information will be treated as confidential material and will be available only 
to research and clinical staff. All data collected will be entered into an electronic database which is stored 
on a secure server (REDCap) that is backed up on a daily basis. Patient identifying information will be 
stored in a separate database and will be password protected and stored on a secure server. All paper 
files will be kept in a locked filing cabinet. Audio recordings will be stored on a secure server or kept in a 
locked filing cabinet. No subject will be identified in any report of the project.  
 
REDCap is a secure, web-based application developed by Vanderbilt University for building and 
managing surveys and databases. It is primarily designed to support online or offline data capture for 
research studies, quality improvement, and operations. REDCap provides easy data manipulation (with 
audit trails for reporting, monitoring and querying patient records), real-time data entry validation, and 
an automated export mechanism to common statistical packages. 
  
Care New England’s instance of REDCap is hosted within the Care New England data center in 
Warwick, RI. This REDCap instance is role-based and is fully integrated with CNE’s Active Directory 
structure. It enjoys 24/7/365 enterprise-level support and security inherit to CNE’s HIPAA-compliant 
data center. Network transmissions (data entry, survey submission, and web browsing) to and from 

 
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REDCap are protected via TLS 1.2 encryption.  REDCap’s data is stored on encrypted servers within CNE’s 
data center. 
  
The REDCap Consortium is composed of thousands of active institutional partners in over one 
hundred countries who utilize and support REDCap. REDCap was developed specifically around HIPAA-
Security guidelines, and more information about the consortium and system security can be found 
at http://www.projectredcap.org/.  
 
Due to the nature of text messaging technology, there is a small, but potential, privacy risk when 
communicating through text messages. Text message communications are not encrypted and therefore 
this information can be read if intercepted while in transit.  Although we have a strict patient 
confidentiality policy there is a possibility for the text messaging communications to be intercepted or 
accessed without the participant's authorization. This will be made clear in the informed consent process, 
and we will remind participants not to send sensitive information by text.  It is important to note that we 
will only be conveying general information by text messaging. No confidential or sensitive information 
will be sent by text message at any time.  Text messages will contain information about scheduling only. 
Text messages will be sent from a dedicated password-protected study cell phone. The loss of privacy is a 
serious risk but we believe that it is highly unlikely as we have extensive experience taking measures 
appropriate to safeguarding confidential information. Participants may be included in the study even if 
they decline to have text messages sent to them.  
 
 
 
We will ask parents/participants to sign a release of information so that we may communicate 
with their primary care provider and their specialty mental health providers (if any) about a) medical 
clearance for mild/ moderate physical activity; b) any serious mental health concerns that may arise. 
Although this could present a risk to confidentiality, we believe this is outweighed by concerns about the 
patient’s safety.  
 
Finally, being part of a focus group or a group intervention carries with it a risk of loss of privacy. 
We will remind participants of this risk in the informed consent process, and also ask them to keep 
information learned about other group members, including the fact they were in the group, private.  This 
risk may be slightly increased when classes are conducted via videoconference. To decrease this risk, we 
will ask that all participants view video classes in a private location in their home; we will also make sure 
participants understand that we cannot guarantee all participants will do this.  
 
 
Increased distress due to assessment or intervention procedures.  It is possible that some 
adolescents will experience increased intrapersonal or interpersonal psychological distress as a result of 
participating in assessments or intervention. In the vast majority of cases, we believe that any increased 
distress experienced will be mild and transitory in nature. The risks of possible distress due to the 
assessment and treatment procedures will be minimized by:  a) using assessments and procedures which 
have been widely used in previous research studies; b) allowing participants to refuse to answer any 
question or withdraw from the study at any time;  c) training yoga instructors in how to minimize and 
manage distress that may occur in class; and d) having study MPIs Drs. Yen (a licensed clinical 
psychologist with expertise in adolescent suicidality), Uebelacker (a licensed clinical psychologist), and 
co-I Dr. Wolff (a licensed clinical psychologist with expertise in adolescent suicidality), or their designee 
(who will be a licensed health professional) in their absence, on call to counsel participants should they 
report experiencing distress.  
 
  
Physical injury. Because yoga is a physical activity, there is a small risk of physical injury for 
those participants who are in study yoga classes. The risk of physical injury will be minimized by: a) 
requiring all participants in yoga classes to be cleared by their primary care provider for moderate 
physical activity; and b) requiring all instructors to be registered yoga teachers with experience in 
directing people in how to achieve yoga postures without physical injury. Class content will be designed 

 
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to accommodate the needs of yoga-naïve students who are not currently physically active. By presenting 
modifications of all postures, and by using props (e.g., folding chairs, blocks, straps, and blankets), the risk 
for injury will be minimized.  Injuries due to yoga will be monitored at frequent intervals during this part 
of the study.  
 
  
To minimize risk of physical injury for yoga classes conducted via videoconference, we will do all 
of the above. In addition, we will only use poses that have been successfully used in in-person classes. Of 
note, we have had 19 participants enroll in yoga classes as of 3/13/2020, with no adverse events of any 
severity level related to participation in yoga class. Therefore, we believe that conducting yoga via 
videoconference does not result in any increased risk to teens. The initial 1:1 session with a newly 
enrolled participant and the yoga teacher will also include a discussion of ways to decrease risk of injury. 
 
 
 
Ineffective intervention.  It is possible that some participants will not experience improvements 
in depression symptoms. The risk of possible ineffective intervention will be minimized by the fact that 
study participants will continue with their current medication or other treatment for depression. Study 
participants may choose to discontinue study participation at any time.  
 
Given that all participants will have risk factors for suicidality (i.e., depression), some participants 
may experience suicide ideation or behavior in the course of study participation. Significant risk for 
suicide will be defined by QIDS item 12 score of 1 or greater (indicating suicide ideation or intent or 
behavior) OR the report of a desire or intent to hurt oneself to study staff. Whenever staff members 
identify an individual with significant risk for suicidality, we will use a standard protocol for managing 
this problem. Study staff will contact either Dr. Uebelacker, Yen, or Wolff. They will be available during 
regular business hours, and have extensive experience managing this issue. After hours, there is always a 
licensed mental health clinician available on call by cell phone.  
 
 
   
When a clinician is asked to conduct an immediate evaluation, they will conduct a suicide risk 
assessment. The clinician will determine whether it is necessary to take immediate action to prevent the 
participant from causing harm to themselves. If needed, the study clinician may ask to speak to a parent 
and/or have a family member or ambulance bring the person to Butler Hospital or another hospital. If the 
participant is not in immediate danger of hurting themselves, we will take the following actions. First, we 
will work to develop a safety plan with the patient and encourage them to discuss this with their parents 
and/or treatment providers. Second, we will inform the parent(s) (for participants aged 13-17) to ensure 
that they are aware of the seriousness of the participant’s symptoms and their suicidal ideation. If 
participants are 18, we will ask for permission to talk with a family member. Families will receive detailed 
psychoeducation regarding suicide risk including removing potential suicide means (e.g., guns, knives); 
being alert to mood changes, suicidal statements, etc.; and learning how to obtain emergency services. 
Finally, we will contact their primary care physician or other clinician to inform them of the suicidality. 
We will urge the participant/parent to make an appointment with that provider to discuss treatment 
options. Regardless of outcome, suicide assessments are always documented in writing. 
 
 
   Participants may also show significant clinical deterioration, as defined as a QIDS total score of 16 
or greater and an increase in QIDS score of 6 or greater from the previous QIDS assessment. This will also 
trigger a clinical evaluation and a determination of the best course of action for the adolescent based on 
clinical judgment. Typically, this will include notification of a parent and outpatient mental health 
provider (if the participant has one) or offer of referrals to an outpatient provider. Actions could also 
include facilitation of higher levels of care (e.g., inpatient hospitalization).   
 
A participant who has undergone a suicide risk assessment or who has had clinical deterioration 
may continue to participate in the study unless the study PIs, in concert with the participant’s parent and 
healthcare providers, deem study participation to increase risk for this particular participant. Participants 
who are hospitalized due to concerns about suicidality may be discontinued from the study if parents/ 

 
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clinicians/ MPIs determine it to be in the best interest of the participant. However, they may also continue 
if that is determined to be in the best interest of the participant.  
 
Additional Protections for Vulnerable Subjects 
For study participants who are minors (ages 13-17), parental consent will be required in addition 
to assent. We will ensure that adolescents and their parent(s) are fully informed of the purposes and 
procedures of the study both verbally and through a written description contained on the assent/consent 
forms. As an additional protection to research participants who are minors, all participants will be 
informed that disclosure of information regarding abuse will result in reporting the event to appropriate 
state authorities. Participants will also be informed that any disclosure regarding potentially life-
threatening behavior – e.g., severe suicidal ideation, IV drug use – will be reported to their therapists 
and/or primary care provider and parents. When a report to a parent is made, we will also ensure that 
families will receive detailed psychoeducation regarding suicide risk including removing potential suicide 
means (e.g., guns, knives); being alert to mood changes, suicidal statements, etc.; and learning how to 
obtain emergency services. It is possible that situations will arise in which research assistants or group 
leaders are provided with information by adolescents or parents which they are legally and ethically 
obligated to disclose (e.g., suicidal or homicidal intent, harsh disciplinary practices, sexual abuse). All 
participants are informed in advance through the process of informed consent of the legal and ethical 
obligations of study staff should these issues arise. Whenever possible, study staff will handle these 
situations therapeutically. For example, if time limits and safety concerns allow, parents will be informed 
in advance that a report must be made and provided the opportunity to participate in the mandated 
report process. Research staff will contact the MPIs who will be responsible for any on-site clinical 
decision-making. 
 
Potential Benefits 
 
Potential benefits include: enjoyment of yoga classes or better physical health (for those taking 
yoga) and increased knowledge about coping skills (for those randomized to group CBT). Potential 
benefits of the focus groups include the opportunity to provide input on how to manage an important 
clinical problem.  
 
Risk-Benefit Ratio. 
 
We believe that most serious risks (e.g., loss of confidentiality, major psychological distress due to 
study participation, or serious physical injury due to yoga participation) to subjects are very unlikely. We 
have attempted to minimize these risks (described above). While some risks may be more likely to occur 
(e.g., minor, transient psychological distress), these risks are much less serious. The risk of ineffective 
treatment is a serious risk, but one which: 1) is minimized through safeguards described above; 2) is 
common to any treatment for depression. Therefore, the potential benefits of the proposed study seem to 
outweigh the potential risks of this study for the individual participants. 
7.1 
Specification of Safety Parameters 
Safety issues will be minimal in Phase 1 given that participation involves only a single focus group, 
no yoga classes, and no formal assessment of suicidality. However, should an issue arise (e.g., a voluntary 
report of suicide ideation from one of the adolescent participants), staff would manage it in the same way 
that they would manage it in Phases 2 and 3.  
 
Please see Table 3 for a summary of safety issues, how they are assessed, when they are assessed, and 
relevant staff actions. 
 
 
 

 
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Table 3. Assessment and Management of Safety Issues, Summary, Phases 2 and 3.  
 
Safety Issue 
How assessed 
When Assessed in 
Phase 2/Phase 3 
Relevant Research Staff Actions 
Suicidality 
QIDS, 
BDI, 
MINI 
Participant/parent 
report to research staff 
B1, M1, M2, M3, M6*, M9* 
B1, M3, M6*, M9* 
Any point 
Immediate clinical assessment as 
described in DSMP 
Clinical 
deterioration 
Change in QIDS score 
M1, M2, M3, M6*, M9* 
Immediate clinical assessment as 
described in DSMP 
Injuries due 
to yoga 
Structured self-report 
Weekly during first 3 
months 
Follow until resolution; may result in 
changes to yoga instructor manual 
Pregnancy 
Single interview 
question 
BL1 (exclusion) 
M1, M2 
Discontinuation from intervention 
Other AEs 
SAFTEE 
CASA 
Participant/parent 
report to research staff 
 
M3 
BL1, M3, M6*, M9* 
Any point 
If related to study participation, follow 
resolution; potential changes to 
procedures particularly if AE is also 
unexpected 
 
 
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
See Table 3.  
7.3 
Adverse Events and Serious Adverse Events  
Adverse Event (AE) definition: An adverse event (AE) is any unfavorable and unintended 
diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either 
occurs during the study, having been absent at baseline, or if present at baseline, appears to worsen. 
Adverse events are to be recording regardless of their relationship to the study intervention.   
Serious Adverse Event (SAE) definition: A serious adverse event (SAE) is one that meets one or 
more of the following criteria: 
 
 
Results in death 
 
Is life-threatening (places the subject at immediate risk of death from the event as it occurred; 
includes a suicide attempt or drug overdose) 
 
Results in inpatient hospitalization or prolongation of existing hospitalization 
 
Results in a persistent or significant disability or incapacity 
 
Results in a congenital anomaly or birth defect   
 
An important medical event that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, the event 

 
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may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. 
Study staff will record all reportable events with start dates occurring any time after informed 
consent is obtained at least until the final day of study participation. Each time participants attend yoga 
classes, we will inquire about injuries due to yoga. For all participants in either the open trial or pilot RCT, 
at Month 3 (end of intervention), study staff will administer the SAFTEE in order to inquire about the 
occurrence of AE/SAEs during the previous 3 months. This allows us to systematically assess number of 
adverse events, severity, and resulting impairment.  Finally, any time a participant (or parent) reports an 
adverse event to any staff member, a research assistant will contact the participant or parent or both to 
ascertain information for recording of the adverse event. For adverse events ascertained by any of these 
three possible methods, the research assistant gets information on what happened, start and stop dates, 
severity, functional impact, interactions with healthcare professionals, perceived cause, and possible 
relation to study participation.   
7.4 
Reporting Procedures 
Once staff members report an AE or SAE to MPIs, Dr. Yen or Uebelacker (and only Dr. Uebelacker 
in Phase 3, as she is not blind in Phase 3) will code severity, causal relationship, and whether the event 
was expected. If necessary, she will seek further information from the participant or parent or other 
source before coding.  
 
AEs will be coded on a weekly basis. Any potential SAE will be immediately reviewed by one of the 
MPIs (or a qualified designee in her absence) and coded; this coding will subsequently be reviewed by the 
SMC (Safety Monitoring Committee). Coding of AEs and SAEs occurs on a study AE case report form.   
 
SAEs that are unanticipated, serious, and possibly related to the study intervention will be 
reported to the Safety Monitoring Committee (SMC), IRB, and NCCIH in accordance with requirements.  
We will use the Butler Hospital IRB-approved AE report form. 
 
Unexpected fatal or life-threatening SAEs related to the intervention will be reported to the IRB, 
NCCIH Program Officer, and SMC within 3 days of the investigator becoming aware of the event. 
Other serious and unexpected SAEs related to the intervention will be reported within 7 days. 
These timeframes follow guidance from NCCIH and are consistent to local IRB policies.  
 
Anticipated or unrelated SAEs will be handled in a less urgent manner but will be reported to the 
SMC, IRB, and other oversight organizations in accordance with their requirements, and will be reported 
to NCCIH on an annual basis.  
 
 
Unrelated SAEs that are fatal or life threatening must be reported to the Butler Hospital IRB 
within 7 days of the investigator becoming aware of the event.  
 
Unrelated SAEs that are not fatal or life-threatening must be reported to the Butler Hospital IRB 
annually.  
 
 
All other AEs documented during the course of the trial will be reported to NCCIH on an annual 
basis by way of inclusion in the annual report and in the annual AE summary which will be provided to 
NCCIH and to the SMC. The SMC Report will state that all AEs have been reviewed.  

 
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7.5 
Follow-up for Adverse Events 
Any SAEs related study participation will be followed for outcome information until resolution or 
stabilization. Follow-up reports will be submitted to the IRB, SMC, or NCCIH as required in each specific 
instance.  
7.6 
Safety Monitoring  
The NCCIH requires that all Human Subjects research studies undergo independent monitoring, 
and NCCIH Program Officials will provide specific guidelines to the PI for the study.   
8. INTERVENTION DISCONTINUATION  
Adolescents will be discontinued from an intervention in the following circumstances:  
 
 
If a parent, the adolescent, their primary care provider, or their mental health provider 
does not believe it is in the best interest of the adolescent to continue. As soon as an MPI is 
informed of this, she will speak with the participant about discontinuation. There may be 
circumstances (e.g., worsening depression, an injury in yoga class) when the MPI reaches 
out to a primary care provider, MH provider, or parent to actively inquire if they have 
concerns about the adolescent continuing to participate. 
 
If a parent or adolescent choose to discontinue the adolescent’s attendance.  
 
If one of the MPIs, in consultation with the relevant instructor or therapist, finds the 
adolescent to be so disruptive to the rest of the class that they have a repeated and 
substantive negative impact on the other participants. 
 
If the adolescent does not or is unable to follow guidelines regarding being in a private 
space when participating in the video-based intervention. 
 
Participants will continue with subsequent assessments with their (parent and adolescent) 
permission.  Assessment schedule and assessments used will not change.  
9. STATISTICAL CONSIDERATIONS  
9.1 
General Design Issues  
Our primary overall objective for this pilot project is to develop procedures and manuals, and 
acquire supportive data on feasibility and acceptability that will prepare us to conduct a fully-powered 
non-inferiority design trial of hatha yoga vs. group CBT for depression in adolescents.  
 
Because this is a treatment development study, we have chosen our sample sizes as being 
sufficient to assess feasibility and acceptability. This study is not powered to assess differences (or non-
inferiority) between treatments.  
9.1.1 Summary of Aims, Endpoints, and Data Analytic Strategy.   
Table 4 summarizes each aim, the target endpoint, and the data analysis strategy, where 
applicable.  
 
 

 
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Table 4. Summary of Aims, Endpoints, and Analyses. 
 
Aim/Objective 
Endpoint 
Analyses 
Phase 1 – Focus Groups 
Conduct focus groups with 
adolescents and parents 
Conducted up to 4 focus groups with 
adolescents and parents 
Qualitative analysis – see description 
below. 
Solicit feedback from experts in 
depression, health, and/or yoga in 
adolescents 
Feedback received from experts in 
relevant areas 
Qualitative analysis – see description 
below. 
Create a manual, training materials, 
and fidelity assessment scale for 
instructors 
Draft instructor manual, instructor 
training materials, and fidelity 
assessment scale created 
N/A 
Phase 2 – Open Trial 
Pilot the yoga intervention 
12 adolescents enrolled & follow up 
assessments completed 
N/A 
Assess feasibility, acceptability, and 
safety of both the yoga intervention 
and the comparison group 
 
See Table 5 for a complete list. 
Descriptive statistics for feasibility, 
acceptability, and safety. See Table 
5. 
Via structured interview, elicit 
feedback from adolescents, parents, 
and yoga instructors 
 
Revise draft of instructor manual, 
instructor training materials, and 
fidelity assessment scale 
Qualitative analysis – see description 
below. 
Phase 3 – Pilot RCT, Study A and B 
Pilot RCT of hatha yoga vs. group 
CBT for depression 
34 adolescents enrolled & follow up 
assessments completed (plus any 
Study B participants) 
N/A 
Assess feasibility, acceptability, and 
safety of both the yoga intervention 
and the comparison group 
** This is primary ** 
See Table 5 for a complete list 
(Endpoints examined separately for 
main participants and study B 
participants; also examined 
separately for participants consented 
pre-COVID and post-COVID) 
 
Descriptive statistics (see Table 5) 
and qualitative data analysis 
Assess within-group changes on 
outcomes. The primary outcome will 
be depression symptom severity at 
post-intervention (M3). Secondary 
outcomes include depression 
severity at follow-up (9 months), and 
self-report of depression, functional 
impairment, anxiety, and sleep at 
post-intervention (M3) and 9 months. 
** This is exploratory ** 
Endpoint = post-intervention (M3) 
(Endpoints examined separately for 
main participants and study B 
participants; also examined 
separately for participants consented 
pre-COVID and post-COVID) 
Within-subjects t-tests (e.g., from 
pre-intervention to post-
intervention/M3). We will conduct 
analyses separately by treatment 
group. We will calculate effect sizes 
(Cohen’s d) from pre- to post-
treatment/M3, with corresponding 
confidence intervals. 
Assess within-group changes on 
self-compassion and meta-cognitive 
awareness 
** This is exploratory ** 
Endpoint = post-intervention (M3) 
(Endpoints examined separately for 
main participants and study B 
participants; also examined 
separately for participants consented 
pre-COVID and post-COVID) 
Within-subjects t-tests (e.g., from 
pre-intervention to M3). We will 
conduct analyses separately by 
treatment group. 
9.1.2 Description of Assessment Instruments 
Acceptability and Feasibility. Intervention credibility and patient expectations for intervention 

 
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success at baseline will be measured with the Credibility Expectancy Questionnaire (CEQ) [17]; this is 
administered after their initial class.  The Client Satisfaction Questionnaire (CSQ-8) [18] will be used post-
treatment to assess satisfaction with treatment. We will also use qualitative responses to a detailed post-
treatment interview to gain participants’ and parents’ feedback about intervention components and 
research procedures. Finally, it is critical that the amount of yoga practice at home be measured as 
accurately as possible. Participants will complete a yoga home practice questionnaire on a weekly basis. 
This tool was designed to capture both brief “micro” practice (e.g., focusing on breathing for a few 
minutes) as well as more extended home practice (e.g., engaging in a 15-minute asana routine). The tool 
will yield three indices of home practice: frequency of extended home practice, minutes of extended home 
practice, and frequency of micro home practice.  
 
Participant safety. After each home practice questionnaire (i.e., weekly during the intervention 
period), we will ask participants and parents whether participants experienced any injuries as a result of 
yoga. At the end of the study intervention (M3), we will administer the Systematic Assessment of 
Treatment-Emergent Events – General Inquiry (SAFTEE) [19]. This allows us to systematically assess 
number of adverse events, severity, and resulting impairment.  To assess pregnancy, the adolescent will 
be asked in private whether there is a possibility of pregnancy.  If they report that they may be pregnant, 
either at baseline or during follow-up, they will be excluded from study participation as our yoga protocol 
is not modified for pregnancy. Finally, any time a participant (or parent) reports an adverse event to any 
staff member, a research assistant will contact the participant or parent or both to ascertain information 
for recording of the adverse event. For adverse events ascertained by any of these three possible 
methods, the research assistant gets information on what happened, start and stop dates, severity, 
functional impact, interactions with healthcare professionals, perceived cause, and possible relation to 
study participation.  For more information and details on coding of AEs, please see DSMP.  
 
Note that the QIDS also serves as a safety assessment, as it allows staff to assess a) clinical 
deterioration and b) suicidality. The BDI also assesses suicide. Any suicidality or clinical deterioration 
triggers a risk assessment. An AE/SAE is recorded if the participant meets criteria for an AE/SAE (see 
DSMP)—i.e., makes an attempt to hurt themselves, does hurt themselves, or is hospitalized. Suicide 
ideation or clinical deterioration in and of themselves do not necessarily constitute an AE.   
 
Assessment of depression. In order to characterize the sample, we will assess whether 
participants meet criteria for major depressive disorder using relevant modules of the Mini International 
Neuropsychiatric Interview for Children and Adolescents (MINI-KID [20]).  We will also use the MINI to 
determine whether participants meet exclusionary criteria. Our primary outcome of depression severity 
(adolescent interview) will be assessed using the 16-item QIDS-A-CR [12, 13] which has been 
psychometrically validated for adolescents [14]. The Patient Health Questionnaire – 8 item (PHQ-8;[21]; 
does not include a suicide item) will be used in an interview format for screening purposes only, as it is 
simple to administer.  
 
Assessment of secondary outcomes. Adolescents will complete the Beck Depression Inventory-II 
(BDI; [22], a self-report measure of depression symptom-severity. We will also assess impairment using 
the Columbia Impairment Scale (CIS; [23]), which is a 13-item, self- or parent-report, that measures four 
areas of functioning: interpersonal relations, broad psychopathological domains, functioning in job or 
schoolwork, and use of leisure time. Items are rated on a Likert scale ranging from 0 (no problem) to 4 
(very big problem). Anxiety will be assessed by revised version of the Screen for Child Anxiety Related 
Emotional Disorders (SCARED-R; [24, 25]), a 41-item self-report questionnaire designed to measure 
symptoms and severity of anxiety disorders in children age 8 to 17. We will assess sleep using the 8-item 
PROMIS Sleep Disturbance questionnaire, which has been validated in adolescents [26]. 
 
Assessment of potential mechanisms of action. We will assess metacognitive awareness 
(decentering) with the Toronto Mindfulness Scale (TMS), which has a decentering subscale and a 

 
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curiosity subscale [27]. We will assess self-compassion with the 26-item Self-Compassion Scale (SCS)[28]. 
This scale can yield a general self-compassion score and has previously been used with adolescents [29]. 
 
Other assessments.  Finally, we will use the International Physical Activity Questionnaire (IPAQ) 
[30], a self-report measure of physical activity. We have also adapted this scale to measure amount of 
yoga practice participants engaged in during the follow-up time period. We will assess antidepressant 
medication use with the interview-based Treatment Response to Antidepressant Questionnaire (TRAQ) 
[31]). We will use the Child and Adolescent Services Assessment (CASA)[32] interview to assess other 
mental health treatment.  If a participant is engaged in psychotherapy but the participant and parent are 
unclear as to whether it is CBT, we will use the Psychotherapy Practice Scale-Patient Depression Care 
Version [33] to help determine whether it is likely that the participant is engaged in CBT. This 
questionnaire will be modified to include some open-ended questions about the nature of the 
participant’s psychotherapy.  We will use the Perceived Cohesion scale to assess group cohesion.  
9.2 
Sample Size and Randomization 
9.2.1.  Sample Size  
This project consists of three phases:  In Phase 1, we will conduct focus groups with up to 24 
depressed adolescents and 24 parents. This should be a large enough sample to gain sufficient feedback 
on ways to make yoga classes an acceptable and feasible intervention. In Phase 2, we will pilot the yoga 
intervention in a sample of 12 adolescents. In Phase 3, we will conduct a pilot RCT (n=34; with a 
possibility of 20 additional adolescents in Study B). In Phases 2 and 3, we will assess feasibility, 
acceptability, and safety of the interventions and research design, and examine key outcomes within 
relevant confidence intervals. This phase of the study is not designed to be adequately powered to assess 
efficacy; rather, it is focused on feasibility, acceptability, and safety.  (Text also in DSMP.) 
9.2.2. Treatment Assignment Procedures 
Participants in Phase 3 will undergo randomization. Eligible individuals who consent to 
participate will be randomly assigned to yoga or group CBT. There are separate randomization tables for 
Phase 3/Study A participants and Study B participants. Eligibility (i.e., that the participant meets all 
inclusion criteria) and group (Study A/B) are determined prior to randomization. Our study statistician 
who has no contact with study participants and will have no access to outcome data until database lock, 
will create randomization tables using Microsoft Excel and upload to our data collection system (REDCap) 
prior to the start of recruitment for the pilot RCT. Randomization will be stratified by gender. We will use 
variable sized block randomization, with randomly ordered block sizes of 4, 6, or 8.  
Study staff will not have access to randomization tables. When a person is deemed eligible, study 
staff will verify the stratification variables in REDCap and then click the “RANDOMIZE” button.  
9.3  
Definition of Populations 
All data analysis will use the intent to treat population and use all available data. There is no per 
protocol analysis planned.  
9.4 
Interim Analyses and Stopping Rules 
9.4.1. Interim analysis  
There is no interim data analysis plan.  
Data analysis of Phase 1 qualitative data will occur during and immediately after data collection in 
Phase 1.  
Data analysis of Phase 2 and 3 data will occur at the end of Phase 2, midway through Phase 3, and 
at the end of Phase 3 (for feasibility and acceptability outcomes). (Text also in DSMP.) 

 
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9.4.2 Halting Rules  
If there are any SAEs judged related to the study intervention, we will halt the study intervention 
until an ad hoc safety review is convened with the SMC, MPIs, and other relevant study staff. The safety 
review will determine whether the study should continue per protocol, proceed with enhanced 
monitoring, be further investigated, be discontinued, or be modified and then proceed. (Text also in 
DSMP.) 
Subsequent review of serious, unexpected, and related AEs by the SMC, IRB, the sponsor(s), or 
relevant local regulatory authorities may also result in suspension of further study interventions. The 
study sponsor(s) retain the authority to suspend additional enrollment and study interventions 
/administration of study product for the entire study, as applicable. (Text also in DSMP.) 
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. (Text also in DSMP.) 
9.5 
Outcomes  
9.5.1 Primary Outcome   
There is no single primary outcome, as this is a treatment development study.  
 
We monitor treatment development outcomes (correspondingly described in Table 5) throughout 
Phases 2 and 3. Target outcomes were chosen on face validity, clinical experience, and, when available, 
relevant clinical literature. After the pilot open trial (Phase 2), and at 2 time points throughout the Phase 
3 pilot RCT (i.e., after enrolling 17 patients and 34 patients), the scientific team will convene to discuss 
how our actual procedural outcomes compare to the target outcomes. Discrepancies will result in: 1) 
investigation (using qualitative or other data) of the reason for the failure to meet this outcome; and 2) 
discussion amongst the research team. Depending on the nature of the discrepancy, we may modify 
recruitment procedures, assessment procedures, instructions to participants, instructor training 
procedures, or other aspects of the trial. In addition, Drs. Uebelacker and Caviness and the lead yoga 
instructor will review any adverse events that are possibly, probably, or definitely related to the study 
intervention to determine whether any changes need to be immediately made to the yoga instructor 
manual to prevent such events from occurring in the future.   
 
Primary data analyses will be focused on feasibility and acceptability (see Table 5) using intent-
to-treat population. Study measures and endpoints will continue to be collected for all enrolled 
participants, even in the event of premature discontinuation of the study intervention. To mitigate the 
problem of missing data, our RAs will try to reach participants to encourage them to schedule/complete 
the assessment via multiple methods that a participant (and their parent) have said are acceptable, 
including texting, voicemail, or email. 
 
 

 
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Table 5. Target Outcomes – Phase 2 and 3. 
 
Note: we will look at outcomes for the entire group of enrolled participants for Phase 2 and Phase 
3. In addition, in Phase 3, we will examine outcomes for 2 sets of subgroups:  
a. Study A vs. Study B 
b. Pre-COVID enrollment (including those who participated in some in-person and some video 
classes, which is the majority of the Pre-COVID enrolled group) vs. Post-COVID enrollment 
(i.e., those who consented and started video-based classes from the start).  
.  
9.5.2 Secondary/Exploratory Outcomes   
In both Phase 2 and Phase 3, exploratory outcomes include change in depression, impairment, 
anxiety, and potential mechanisms of action over time.   
 
Specifically, we will look at change over time the in the following variables. The primary outcome in a 
subsequent efficacy study is in bold and underlined. Secondary outcomes are in standard text. Potential 
mechanisms are in italics.  
 
Description 
(Assessment method) 
Target 
Feasibility and Acceptability--  Hatha yoga, CBT 
Acceptability  (qualitative interview) 
Most feedback positive; few substantive negative comments.  Negative comments 
used to enhance procedures. Comments regarding video-based vs.in-person 
classes used to guide decisions about modality for future research. 
Credibility at baseline (CEQ) 
Average > 15 (i.e., midpoint score between low and high credibility) on each of 3 
items 
Expectancy at baseline (CEQ) 
Average > 15 (i.e., midpoint score) on each of 3 items 
Program satisfaction (CSQ-8) 
Average > 24 (or a mean score of 3 on each of the 8 items) 
Home practice (homework 
questionnaire) 
70% of yoga participants engage in home practice at least 2 times per week for 
8/12 weeks. 
Class attendance 
70% of all participants complete 8/12 classes. 
Instructor adherence (Adherence 
measures) 
Yoga instructors achieve at least 80% adherence on a random subset of classes 
taught 
Safety 
Adverse events (SAFTEE; injuries due 
to yoga) 
No serious adverse events or injuries that are possibly, probably, or definitely 
related to study participation.  Any AEs related to study participation might lead to 
changes in yoga manual or other relevant study procedures, particularly if AE is 
unexpected. 
Feasibility and Acceptability—Research Procedures 
Recruitment rate 
Average of 3 enrolled per month 
Retention rate 
At least 90% complete M1 assessment, 85% complete M2 assessment, 80% 
complete post-intervention endpoint (Month 3) assessment, 75% complete M6 and 
M9 follow-up assessments 
Completeness of self-report 
instruments and interviews 
All self-report instruments will have at least 80% of items completed; interviews will 
have at least 90% of items completed 

 
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 
Depression, Adolescent report: change in QIDS from BL to M3; BL to M6 (phase 3 
only), and BL to M9 (phase 3 only) 
 
 
Depression, Adolescent report: change in BDI from BL to M3; BL to M6 (phase 3 only), and 
BL to M9 (phase 3 only) 
 
Depression, Parent report: change in QIDS from BL to M3; BL to M6 (phase 3 only), and BL 
to M9 (phase 3 only) 
 
Depression, Parent report: change in BDI from BL to M3; BL to M6 (phase 3 only), and BL 
to M9 (phase 3 only) 
 
Functional impairment, Adolescent report: change in CIS from BL to M3; BL to M6 (phase 
3 only), and BL to M9 (phase 3 only) 
 
Functional impairment, Parent report: change in CIS from BL to M3; BL to M6 (phase 3 
only), and BL to M9 (phase 3 only) 
 
Anxiety, Adolescent report: change in SCARED-R from BL to M3; BL to M6 (phase 3 only), 
and BL to M9 (phase 3 only) 
 
Anxiety, Adolescent report: change in SCARED-R from BL to M3; BL to M6 (phase 3 only), 
and BL to M9 (phase 3 only) 
 
Sleep Disturbance, Adolescent report: change in PROMIS- Sleep disturbance from BL to M3 
 
 
Mindfulness, Adolescent report:  change in subscales of TMS from BL to M3; BL to M6 (phase 
3 only), and BL to M9 (phase 3 only) 
 
Self-Compassion, Adolescent report: change in SCS from BL to M3; BL to M6 (phase 3 only), 
and BL to M9 (phase 3 only) 
9.6 
Data Analyses  
Qualitative Data Analysis 
Focus groups (Phase 1) or interviews (Phase 2, 3) will be recorded and transcribed. We will use a 
template organizing style to analyze qualitative data [34]. Dr. Uebelacker will oversee the process. She 
will develop an initial codebook with deductive codes. Inductive codes capturing emergent themes will 
arise from team-level review of the transcripts. Once the codes are developed, members of the scientific 
team will independently code remaining transcripts; 20% of transcripts will be double coded and 
reviewed to ensure coding fidelity. Information gleaned will then be reviewed by the scientific team and 
used to modify manuals and procedures.   
 
Quantitative Data Analysis 
In Phase 2 and Phase 3, we will use descriptive statistics to summarize all variables. We will also 
conduct exploratory analyses of change over time in depression (which will be the primary outcome in an 
efficacy study), impairment and anxiety (which will be secondary outcomes) and potential mechanisms of 
action. All variables will be examined and tested for distributional assumptions prior to statistical 
analysis. We will use within-subject t-tests, separated by treatment group. In this study, these analyses 
should be considered exploratory. Any data that violates statistical assumptions will either be 
transformed accordingly and appropriate statistical tests will be applied (e.g., non-parametric approaches 
such as the Wilcoxon signed rank test in lieu of t-tests). We will look at outcomes for the entire group of 
enrolled participants for Phase 2 and Phase 3. In addition, in Phase 3, we will examine outcomes for 2 sets 
of subgroups:  
c. Study A vs. Study B 
d. Pre-COVID enrollment (including those who participated in some in-person and some video 
classes, which is the majority of the Pre-COVID enrolled group) vs. Post-COVID enrollment 
(i.e., those who consented and started video-based classes from the start).  
.  

 
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10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1 Data Collection Forms  
Participants will directly enter self-report data into REDCap, and data collected as part of an 
interview will be written on a paper CRF and double-entered into REDCap.  For the RCT (Phase 3), there 
will be two REDCap databases – a “blind” database and a “nonblind” database.  As described in the 
assessment table, some assessments are described as being collected by a blind evaluator (research 
assistant), whereas some are not (because these assessments, by their nature, would break the blind.)  
There will also be a database that we will use for tracking participants.   
Any data, forms, reports, audiorecordings, and other records that leave the site will be identified 
only by a participant identification number (Study ID, SID) to maintain confidentiality. All paper records 
will be kept in a locked file cabinet. All data collected will be entered into an electronic database which is 
stored on a secure server (REDCap) that is backed up on a daily basis. Participant identifying information 
will be stored in a separate database and will be password protected and stored on a secure server. Care 
New England’s instance of REDCap has been deemed HIPAA compliant by CNE Information Technology. 
10.2 Data Management  
All self-report data will be collected via REDCap.  Interviews (e.g., MINI, QIDS) have standardized 
forms which we will use and which will be double-entered into REDCap. Any discrepancies will be 
resolved by the Project Manager in consultation with the MPIs as needed.  
 
Please see also “Data Handling and Record Keeping” in the DSMP.  
10.3 Quality Assurance  
10.3.1 Training 
All research personnel, including yoga instructors will have formal training in research with 
human subjects (e.g., CITI training, NIH Human Subjects training). Drs. Yen, Uebelacker, Wolff, and 
Caviness will provide training to and supervise research assistants. Research assistants will also have 
training in Good Clinical Practice. MPIs and Dr. Wolff will provide training on the MINI and QIDS through 
didactic teaching, role plays, and feedback on audiotaped sessions. Dr. Uebelacker will provide training 
and supervision to yoga instructors, and CBT group leaders. Ms. Conti (our lead yoga instructor) will 
assist with yoga instructor training and supervision.  
10.3.2 Quality Control Committee  
Drs. Uebelacker, Yen, Wolff, and Caviness will be responsible for quality control of this study. They 
review recruitment and retention reports, and AE reports, on weekly basis.  
10.3.3 Metrics 
QIDS Reliability 
Research assistants will be trained to administer the QIDS and will be considered certified once 
they rate 5 practice QIDS to a gold standard rating with an ICC of .80 or greater for total scores. 
Subsequently, Dr. Yen, Wolff, or Uebelacker will rate 10% of all QIDS administered. Significant 
discrepancies (greater than 2 for the total score) will be grounds for re-training.  
10.3.4 Protocol Deviations 
During weekly study meetings, protocol deviations will be discussed with the MPIs, including 
plans for corrective action. Dr. Caviness will also be alerted to deviations as they occur and will alert the 
MPIs for any deviation requiring immediate action. Protocol deviations will be logged on the protocol 
deviation tracking sheet and filed in the regulatory binder. 

 
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All assessment time points have a window of time for completion. However, typically due to 
circumstances outside of the control of the research staff, assessments occasionally occur outside of that 
window. Assessments that occur outside of the recommended window for completion will be considered 
to be protocol deviations, and will be logged as such.  
 
Protocol deviations will be reported to NCCIH once per year, in the annual review. The SMC will 
also receive a list of protocol deviations in their interim or annual reports.  Per Butler Hospital IRB policy, 
“major protocol deviations/violations, defined as those which increase risk to participants” will be 
reported promptly to the IRB and no more than 10 working days after the investigator is aware of the 
event. Minor protocol deviations do not need to be reported.  
10.3.5 Monitoring 
Dr. Caviness (or Dr. Uebelacker, in her absence) will inspect BL documents (consent forms, release 
of information) for completeness within a week after they are signed.  Dr. Caviness will also conduct 
protocol and data quality monitoring twice a year using the Quality Management review checklists. 
During Phase 2, all participant and other study records will be reviewed. During Phase 3, a random 
sample or 15-20% of participant and study records will be reviewed at each monitoring time point.  
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 Institutional Review Board (IRB) Review  
This protocol and the informed consent documents and any subsequent modifications will be 
reviewed and approved by the IRB or ethics committee responsible for oversight of the study. The 
consent form should be separate from the protocol document.  
11.2 Informed Consent Forms 
A signed consent form will be obtained from each participant (adolescent or parent/legal 
guardian) aged 18 or older. For participants who cannot consent for themselves (i.e, adolescents aged 17 
or younger), the parent/legal guardian must sign the consent form, and the adolescent will sign an assent 
form. The consent/assent forms will describe the purpose of the study, the procedures to be followed, and 
the risks and benefits of participation. A copy will be given to each participant and parent/legal guardian 
and this fact will be documented in the participant’s record.  When an e-signature is used, we will follow 
procedures outlined by the Butler Hospital IRB for obtaining that signature.  
11.3 Participant Confidentiality  
Any data, forms, reports, audio recordings, and other records that leave the site will be identified 
only by a participant identification number (Study ID, SID) to maintain confidentiality. All paper records 
will be kept in a locked file cabinet. All data collected will be entered into an electronic database which is 
stored on a secure server (REDCap) that is backed up on a daily basis. Participant identifying information 
will be stored in a separate database and will be password protected and stored on a secure server. Care 
New England’s instance of REDCap has been deemed HIPAA compliant by CNE Information Technology. 
 
Information will not be released without written permission of the participant, except as 
necessary for monitoring by IRB, the FDA, the NCCIH, and the OHRP. 
11.4 Study Discontinuation  
The study may be discontinued at any time by the IRB, the NCCIH, the OHRP, the FDA, or other 
government agencies as part of their duties to ensure that research participants are protected.  

 
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12. COMMITTEES 
There will be a Data and Safety Monitoring Board.  
13. PUBLICATION OF RESEARCH FINDINGS  
Drs. Yen and Uebelacker will be responsible for oversight and approval of any publications or 
presentations that arise from this research. 

 
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15. SUPPLEMENTS/APPENDICES 
 
None.