Mindful Body Awareness Training as an Adjunct to Medication Treatment for Opioid Use Disorder
Phase: NA
Conditions: Opioid-use Disorder
Sponsor: University of Washington

 
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Cover page for Clinicaltrials.gov 
Official Title: Study Protocol for ‘Mindful Body 
Awareness with Medication Treatment for 
Opioid Use Disorder’ 
NCT Study #: 04082637 
Document Date: October 20, 2021 
Document Approval for UW IRB: Nov 15, 2021 
 
 

 
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MABT for OUD 
Protocol 
 
 
 
 
 

 
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PREFACE 
The objective of this study is to test the effectiveness of an innovative body-oriented therapy 
found to reduce substance use and improve related health outcomes as an adjunct to opioid 
use disorder (OUD) treatment.  The long-term study goal is to improve OUD treatment 
outcomes.  Body-oriented therapy combines manual and mind-body elements and is focused 
on improving sensory and emotional awareness.  The approach, Mindful Awareness in Body-
oriented Therapy (MABT), involves body awareness (e.g. interoception) training to provide 
somatically-based tools for self-care to facilitate emotion regulation.  Research suggests that 
only half of persons who are treated with buprenorphine are retained in maintenance 
treatment beyond 6 months, and when not taking medications patients frequently relapse to 
illicit opiate use. Chronic pain has been identified as a major factor that may lead to 
treatment failure. In a sample of patients on MAT, we demonstrated that patients with 
chronic pain were more likely to report cravings for opiates. Chronic pain is unfortunately 
common among persons with OUD: studies suggest that the majority of patients on 
methadone and buprenorphine suffer from chronic pain.  
 
Relapse prevention is critical to positive outcomes in opioid abuse treatment and studies 
indicate that stress, negative affect and poor emotional regulation are associated with 
vulnerability to relapse.  MABT has the potential to address relapse to substance use, chronic 
pain and its associated stress, and thus improve treatment outcomes among patients being 
treated for OUD with buprenorphine. 
 
There is a compelling need for adjunctive therapies to maximize treatment outcomes for 
patients who are receiving buprenorphine for OUD treatment.  This research study responds 
to the need to test new OUD treatments, particularly innovative approaches that target 
interoception and emotion regulation to enhance treatment outcomes.  This study will be 
implemented through the Opioid Strategic Targeted Response (STR) program. Consistent with 
RFA-AT-18-001, Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to 
Medication Assisted Treatment-SAMSHA Opioid STR Grants, and RFA-AT-19-007, HEAL 
Initiative Limited Competition: Behavioral Research to Improve MAT: Ancillary Studies to 
Enhance Behavioral or Social Interventions to Improve Adherence to Medication Assisted 
Treatment for Opioid Use Disorders (R01 Clinical Trial Optional), the proposed project 
expands the study of MABT to MAT of OUD, with an emphasis on comorbid pain.  
 
For more information contact Cynthia Price at the University of Washington: 
 
Cynthia Price, PhD 
UW School of Nursing, Box 357266 
1959 NE Pacific St. Seattle, WA 98195 
206-685-4739 
cynthiap@uw.edu  
 
 

 
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Mindful Body Awareness Training as an Adjunct to Medication 
Assisted Treatment for Opioid Use Disorder 
 
 
 
Principal Investigators:   
Cynthia J. Price, PhD, Associate Research Professor, University of Washington 
Joseph O. Merrill, MD, Professor, University of Washington 
 
 
 
Supported by:  
The National Center for Complementary and Integrative Health 
Grant Numbers R21/R33AT009932, and R01AT010742 
 
 

 
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Tool Revision History 
Version Number: 1.0 
Version Date:  December 6, 2018 
Informed Consent Version:  1.0 (approved 12/21/2018) 
 
Version Number: 2.0 
Version Date:  January 22, 2019 
Informed Consent Version:  1.0 (approved 12/21/2018) 
Informed Consent Version:  1.1 (approved 3/20/2019) 
Summary of Revisions Made:  
• 
Changed performance site from Evergreen Treatment Services to Country Doctor Community 
Health Centers 
• 
Revised Objective 1 to include a focus on emotional well-being. 
• 
Two measures focused on emotional well-being added. 
• 
Supervision of MABT therapists to be done by Ms.Wiechman (not by Dr. Price).  
• 
Clarifications made to document, in response to Dr. Boineau January 18 review.   
 
Version Number: 3.0 
Version Date:  November 7, 2019 
Informed Consent Version:  1.1 (approved 3/20/2019) 
Informed Consent Version:  1.2 (approved 8/2/2019) 
Informed Consent Version:  1.3 (approved 10/4/2019) 
Informed Consent Version:  2.0 (approved 10/16/2019) 
Summary of Revisions Made:  
• 
Adapted Clinical Protocol to include extension of activities of R01 proposal: 
o 
Extend follow-up to five assessments over one year 
o 
Add North Olympic Healthcare Network as recruitment site 
o 
Increase total sample size to 330 
o 
Offer a stepped-care approach to MABT participants at six months 
• 
Added personnel information to study contacts 
• 
Require HIPAA permission to participate in research study 
• 
Randomization occurs in a Microsoft BASIC program and the algorithm is described 
• 
Added source documentation by Clinical Staff at time of referral for 2 eligibility criteria: OUD and 4 
weeks of buprenorphine Rx  
• 
Specified use of an adapted 7-item Mini-Mental Status Exam in case of concern for 
comprehension of consent or cognitive difficulties (ie head injury)  
• 
Expanded to licensure required for MABT therapists to include either LMT or MSW/LMHC.  
• 
Clarified allowable study visit windows, and optimization of data collection during ideal collection 
windows 
• 
Non-substantive changes to update described procedures such as when screening ID number is 
assigned, collecting preferred participant contact methods, etc. based on further communications 
with clinical sites and training/practice experience with new staff. 
 

 
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Version Number: 4.0 
Version Date:  October 20, 2021 
Informed Consent Version:  1.1 (approved 3/20/2019) 
Informed Consent Version:  1.2 (approved 8/2/2019) 
Informed Consent Version:  1.3 (approved 10/4/2019) 
Informed Consent Version:  2.0 (approved 10/16/2019) 
Informed Consent Version:  3.0 (approved   9/02/2021) 
 
Summary of Revisions Made:  
• 
Added Clinical Site, Cascade Medical Advantage (CMA) in Bellingham, WA  
o This addition was taken to replace Country Doctor Clinic, where we stopped 
recruitment in May, 2021 due to insufficient support for enrollment by clinic staff.  
• 
Added Clinical Site, Evergreen Treatment Services (ETS) in Seattle, WA  
o Since ETS is a methadone clinic (other clinical sites prescribe buprenorphine), 
we amended our eligibility criteria so that it aligned with the overall focus on 
stability in treatment (as at other sites) but addressed medication dispensing 
procedures for methadone.  
o Amended our informed consent so it could be used at all clinical sites, including 
ETS. This involved minor shifts in language (i.e. removing reference to 
buprenorphine and referring more broadly to medication for OUD treatment); see 
approval noted above on 9/2/21.  
• 
Updated Study Roster 
• 
Updated Study Clinical Sites 
• 
Unsubstantial/minor revisions: updated language throughout to reflect focus on 
medication for OUD (vs. buprenorphine specifically). 
 
 
 

 
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TABLE OF CONTENTS 
                                                   
MABT for OUD Protocol ................................................................................... 1 
PREFACE ..................................................................................................... 4 
Tool Revision History .................................................................................... 6 
TABLE OF CONTENTS ..................................................................................... 9 
STUDY TEAM ROSTER ................................................................................... 11 
PARTICIPATING STUDY SITES .......................................................................... 11 
PRÉCIS .................................................................................................... 12 
1. STUDY OBJECTIVES ................................................................................... 14 
1.1 
Primary Objective ............................................................................. 14 
1.2 
Secondary Objectives ......................................................................... 14 
2. BACKGROUND AND RATIONALE ..................................................................... 15 
2.1 
Background on Condition, Disease, or Other Primary Study Focus ..................... 15 
2.2 
Study Rationale ................................................................................ 18 
3. STUDY DESIGN ......................................................................................... 20 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS ............................................... 22 
4.1 
Inclusion Criteria .............................................................................. 23 
4.2 
Exclusion Criteria .............................................................................. 23 
4.3 
Study Enrollment Procedures ................................................................ 23 
5. STUDY INTERVENTIONS ............................................................................... 25 
5.1 
Interventions, Administration, and Duration .............................................. 25 
5.2 
Handling of Study Interventions ............................................................. 25 
5.3 
Concomitant Interventions ................................................................... 26 
6. STUDY PROCEDURES .................................................................................. 27 
6.1 
Schedule of Evaluations....................................................................... 27 
6.2 
Description of Evaluations .................................................................... 27 

 
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7. SAFETY ASSESSMENTS ................................................................................ 34 
7.1 
Specification of Safety Parameters ......................................................... 34 
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters .... 34 
7.3 
Adverse Events and Serious Adverse Events ............................................... 35 
7.4 
Reporting Procedures ......................................................................... 36 
7.5 
Followup for Adverse Events ................................................................. 37 
7.6 
Safety Monitoring .............................................................................. 37 
8. INTERVENTION DISCONTINUATION ................................................................. 37 
9. STATISTICAL CONSIDERATIONS ..................................................................... 38 
9.1 
General Design Issues ......................................................................... 38 
9.2 
Sample Size and Randomization ............................................................. 40 
9.3  
Definition of Populations ..................................................................... 41 
9.4 
Interim Analyses and Stopping Rules ........................................................ 41 
9.5 
Outcomes ....................................................................................... 42 
9.6 
Data Analyses .................................................................................. 44 
10. DATA COLLECTION AND QUALITY ASSURANCE ................................................. 45 
10.1 
Data Collection Forms ........................................................................ 45 
10.2 
Data Management ............................................................................. 45 
10.3 
Quality Assurance .............................................................................. 46 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY .................................................. 47 
11.1 
Institutional Review Board (IRB) Review ................................................... 47 
11.2 
Informed Consent Forms ...................................................................... 47 
11.3 
Participant Confidentiality ................................................................... 48 
11.4 
Study Discontinuation ......................................................................... 48 
12. COMMITTEES .......................................................................................... 48 
13. PUBLICATION OF RESEARCH FINDINGS ........................................................... 48 

 
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14. REFERENCES .......................................................................................... 49 
 
STUDY TEAM ROSTER  
 
Name 
Role 
Address 
Phone 
Fax 
Email 
Cynthia Price 
PI 
UW SON 
206-685-4739 
206-685-9264 
cynthiap@uw.edu 
Joseph Merrill 
PI 
Harborview 
206-774-1834 
206-774-1834 
joem@uw.edu 
Judith Tsui 
Consultant 
Harborview 
206-744-1835 
206-774-1834 
tsuij@uw.edu 
Jean Charette 
Project 
Administrator 
UW SON 
206-543-8674 
206-685-9264 
jeanc20@uw.edu 
Anna Treadway 
Project 
Coordinator 
UW SON 
206-728-0337 
206-685-9264 
annajean@uw.edu 
Kenneth Pike 
Data Manager 
& Statistician 
UW SON 
206-221-2415 
206-685-9264 
kenpike@uw.edu 
Karin Gordon 
Interventionist UW SON 
206-771-0060 
206-685-9264 
karin@uw.edu 
Zoe Bermet 
Interventionist ETS 
206-462-0689 
206-685-9264 
bermetz@uw.edu 
Robert 
Puaokalani 
Interventionist NOHN 
360-461-8703 
206-685-9264 
Robp17@uw.edu 
Brianna Noach 
Interventionist NOHN 
360-477-9944 
206-685-9264 
bnoach@uw.edu 
Carla Wiechman 
MABT Trainer 
and Supervisor 
UW SON 
206-487-2020 
206-685-9264 
carlaw2@uw.edu 
John Astgen 
Research 
Coordinator 
NOHN 
360-809-8810 
206-685-9264 
jastgen@uw.edu 
Vanessa  
Romero-Harry   
Research 
Coordinator 
CMA 
360-410-4961 
206-685-9264 
Romerv2@uw.edu 
Julia Palmer 
Research 
Coordinator 
Harborview 
206-327-0312 
206-685-9264 
Juliak3@uw.edu 
Esther Ricardo-
Bulis 
Research 
Coordinator 
ETS 
206-223-9345 
206-685-9264 
Esther7@uw.edu 
• 
University of Washington School of Nursing, 1959 NE Pacific St, Box 357266, Seattle, WA 98195 
• 
Harborview Medical Center, 325 Ninth Ave, Seattle, WA 98104 
• 
Cascade Medical Advantage, 800 E Chestnut St., Suite 3A, Bellingham, WA 98225 
• 
Evergreen Treatment Services, 1700 Airport Way S, Seattle, WA 98134 
• 
North Olympic Health Network, 933 E 1st St, Port Angeles, WA 98362 
 
PARTICIPATING STUDY SITES and SITE PIs 
Name 
Site 
Address 
Phone 
Fax 
Email 
Joseph Merrill 
Harborview 
Medical 
Center 
325 Ninth 
Ave, 
Seattle, WA 
98104 
206-774-1834 
206-774-
1834 
joem@uw.edu 
Kristine Johnson 
North Olympic 
Healthcare 
Network 
933 E 1st St, 
Port 
Angeles, WA 
98362 
360-452-7891 
ext 2878 
360-452-
8087 
kjohnson@nohn-
pa.org 
 
Glenna Martin 
Country 
Doctor 
Community 
500 19th 
Ave. E, 
Seattle, WA 
206-299-1600 
206-299-
1997 
Gmartin@cdchc.org 

 
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Health 
Centers 
98112 
Paul Grekin 
Evergreen 
Treatment 
Services 
1700 Airport 
Way S., 
Seattle, WA  
98134 
206-223-3644 
x232 
206-685-
9264 
grekin@evergreentr
eatment.org 
Adam Kartman  
Cascade 
Medical 
Advantage 
800 E. 
Chestnut 
St., Suite 3A 
Bellingham, 
WA 98225 
362-927-1502 
206-685-
9264 
akartman@cascade
medicaladvantage.
org 
 
PRÉCIS  
Study Title  
Mindful Body Awareness Training (MABT) as an Adjunct to Medication Assisted 
Treatment (MAT) for Opioid Use Disorder 
Objectives  
1. The primary objective is to evaluate the effectiveness of MABT + TAU compared to TAU 
only in reducing opioid use (OU) and other illicit substances (e.g. methamphetamines, 
etc.).  
 
2. To examine the effectiveness of MABT + TAU to improve mental and physical health 
compared to TAU only.  
 
3. To examine the effectiveness of MABT + TAU to positively affect substance use related 
outcomes of craving and treatment retention compared to TAU only.   
 
4. To explore the effectiveness of additional MABT dose offered at 6 months to those with 
continued substance use (non-responders) compared to those with continued substance use at 
6 months in TAU. 
 
Design and Outcomes   
A two-group (n = 165/165), randomized, repeated measures design will be employed in 
enrolled patients with opioid use (OU) disorder, who will be individually randomized within 
sites to receive MABT+TAU (experimental group), or TAU alone (control). MABT will be 
delivered as a stepped-care approach, involving an initial set of eight weekly sessions, with an 
additional six MABT sessions offered at six months to those with continued substance use in 
intervention arm.  Assessments (surveys and toxicology screens) will be administered at 
baseline, post-intervention (3 months), and at 6 month, 9 month, and 12 month follow-up. 
Analyses at 12 months with a larger sample will examine long-term health outcomes of MABT 
+TAU compared to TAU only on:  1) opioid use and use of other non-opioid substances, 2) 
mental health (depression, anxiety, trauma), emotion regulation, and physical health 

 
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(symptoms, pain severity, pain interference); and 3) opioid craving and treatment retention. 
An exploratory aim will examine the effectiveness of additional MABT dosing for those in the 
MABT treatment arm with continued substance use (nonresponders) at six months compared 
to those with continued substance use (nonresponders) in the TAU arm.  
 
Table 1. Measurement Schedule 
Concept 
Measure 
Assessment Time-Point (from baseline) 
 
 
Baseline  
12 weeks  24 weeks 
39 weeks 
52 weeks 
Baseline and Descriptive Information 
 
 
 
 
 
Demographic/Health 
History  
Health History 
Form[1],(EHR) 
X 
 
 
 
Trauma history  
TLEQ[2] 
X 
 
 
 
 
Economic Indicators 
Employment, Health 
Utilization, Legal 
Status 
X 
X 
X 
X 
X 
Substance Use  
 
 
 
 
 
 
Substance use   
TLFB Interview[3, 4] 
Opioid Craving [5] 
Treatment Retention 
(EHR)  
X 
X 
X  
X 
X 
X  
X 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
Mental Health Distress, Emotional Well-being, 
Physical Health Distress and Pain 
 
 
 
 
 
Distress  
(Depression, Anxiety 
PTSD Symptoms) 
PHQ-9[6, 7] 
GAD-7[8] 
PCL-5[9] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Emotional Regulation 
Difficulties 
 
DERS-SF[10] 
 
X 
 
X 
 
 X 
 
 X 
  
 
 X 
  
 
Mindfulness and 
Interoceptive 
Awareness Skills  
FMQ [14] 
MAIA [15] 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
Co-morbid Pain and 
Interference 
BPI[18] 
X 
X 
X 
X 
X 
Physical Symptoms 
MSC [19] 
X 
X 
X 
X 
X 
Intervention Satisfaction 
 
 
 
 
 
Treatment satisfaction 
and perceived skills* 
MABT Follow-up 
Questionnaire 
 
X 
 
 
 
*MABT Group only; EHR = Electronic Health Records. 
Interventions and Duration  
All study participants receive medication treatment for OUD with OUD treatment monitoring 
by a nurse care manager or medical provider (treatment as usual, or TAU) continually 
throughout the 12 month study.  Those randomized to the intervention group will additionally 
receive Mindful Awareness in Body-oriented Therapy (MABT).  The MABT protocol calls for 
eight sessions to be delivered over a 12 week period between baseline and the 12 week post-
intervention assessment.  At six months, those in the MABT+TAU treatment group with 
continued substance use will be offered an additional six sessions of MABT between the six 
month and 9 month assessments. Follow-up for all participants will total 12 months from the 
participant’s first assessment point. 
Sample Size and Population  
330 male and female individuals who have been receiving MAT treatment for at least four 

 
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weeks will be recruited from three OUD clinical treatment sites.  Each study arm will include 
165 participants.  Participants will be randomized within site, and stratified by sex and self-
reported chronic pain; objectives and outcomes will not vary by strata. 
We expect the clinical characteristics of study subjects to be similar to those enrolled in the 
SAMHSA Medication Assisted Treatment – Prescription Drug and Opioid Addiction (MAT-PDOA) 
project in Washington State. The patients at the two clinics have near equivalence in the 
numbers of men and women served, and age range (18 - 70 years old) with the majority (59%) 
under the age of 35. Most patients are white, low-income, have at most a high school 
education, and are on public insurance (Medicare or Medicaid), with substantial mental health 
and substance use co-morbidity. Approximately 25% are minorities. 
1. STUDY OBJECTIVES 
1.1 
Primary Objective 
Primary Objective and Hypotheses 
The primary objective is to evaluate the effectiveness of MABT + TAU compared to TAU only 
in reducing opioid use (OU) and other illicit substances (e.g. methamphetamines, etc.).  
Primary hypothesis: MABT+TAU will result in significantly fewer days of OU compared to 
TAU only from baseline to to 12 months. 
Secondary hypothesis: MABT+TAU will result in significantly fewer days of non-opioid illicit 
drugs compared to TAU only from baseline to  12 months.  
1.2 
Secondary Objectives 
1) To examine the effectiveness of MABT + TAU to improve mental and physical health 
compared to TAU only.  
Hypothesis: MABT+TAU will result in significantly improved symptoms of mental health 
distress (depression, anxiety, trauma), emotion regulation, interoceptive awareness and 
mindfulness skills, and physical health distress and pain (symptoms, pain severity, pain 
interference) compared to TAU only from baseline to 12 months. 
 
2) To examine the effectiveness of MABT + TAU to positively affect substance use related 
outcomes of craving and treatment retention compared to TAU only.   
Hypothesis: MABT + TAU will result in significantly reduced craving for opioids, and 
significantly longer retention (days receiving medications), compared to TAU only from 
baseline to 12 months. 
 
3) To explore the effectiveness of additional MABT dose offered at 6 months to those with 
continued substance use (nonresponders) compared to those with continued substance use at 
6 months in TAU. 
Hypothesis:  Among participants in both groups who are using substances at 6 months, 
those in MABT group who receive additional MABT sessions (between 6-9 months) will 

 
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show improved substance use at 12 months compared to those in TAU. 
. 
2. BACKGROUND AND RATIONALE 
2.1 
Background on Condition, Disease, or Other Primary Study Focus 
 
Federal and State Response to a National Crisis. Opioid use disorder is a public health 
epidemic of national significance, as demonstrated by federal efforts to target significant new 
public resources to address factors contributing to the continued rise in opioid related 
deaths.[20] The most effective intervention, which has been shown to reduce drug use, 
morbidity and mortality related to opioid use disorder, is Medication Assisted Treatment 
(MAT) with buprenorphine and methadone. Thus, a substantial portion of federal assistance is 
targeted at improving access to MAT, especially through Opioid State Targeted Response 
grants administered through states by SAMHSA. The Washington State Opioid State Targeted 
Response (WA-STR) grant is an $11.7 million per year project. WA state funded projects 
include prevention projects aimed at opioid prescribing practices and projects supporting 
treatment of OUD. The largest single project ($4 million per year) is the Hub and Spoke (H&S) 
project, which funds six OUD treatment networks in Washington State. This adaptation of the 
Vermont Hub and Spoke model funds six networks that each provides referral and/or 
treatment services through primary care clinics, behavioral health programs, and substance 
use disorder (SUD) treatment programs. Washington State was recently awarded over $21 
million for its State Opioid Response (SOR) project, which is expected to continue currently 
funded WA-STR projects as well as funding new initiatives. 
The research proposed here will be conducted through a WA-STR/SOR-funded H&S program 
taking place at Harborview Medical Center (HMC). The network expands ongoing work funded 
through the SAMHSA Medication Assisted Treatment – Prescription Drug and Opioid Addiction 
(MAT-PDOA) project in Washington State, which is piloting the expansion of MAT with 
buprenorphine through a primary care clinic and other Opioid Treatment Programs using the 
Massachusetts Nurse Care Manager (NCM) model. Other treatment models are also included in 
this study, depending on clinical site.  
Need for Behavioral Interventions to Prevent Relapse and Address Mental Health and 
Chronic Pain Among Patients Treated with MAT for OUD. MAT has been shown to reduce 
illicit opiate use and improve health outcomes for patients with OUD;[21-29] however, not all 
patients will benefit, as treatment retention rates are unacceptably low. Data suggests that 
retention may be more of a problem for patients treated with buprenorphine compared to 
methadone: a secondary analysis of clinical trials found that retention at 24 weeks was 46% 
among buprenorphine treated patients compared to 74% among methadone treated patients 
(p<0.01).[30] Estimates of buprenorphine retention in real-world office-based settings show 
that approximately a half, or less, of patients who are initiated in treatment are still retained 
a year later.[31-34] Studies with Kaplan Meier data demonstrate a steep drop-off early in 
treatment with median retention ranges 3–9 months.[32, 35, 36] Clearly there is an 

 
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opportunity to intervene with patients initiating treatment with MAT to improve retention 
rates. The most common reason for patients to become disengaged and not be retained in 
care is relapse to substance use.[31] In addition, upon entering MAT, the majority (~52%) use 
multiple substances [37-40] and there is a high prevalence (34–57%) of co-morbid psychiatric 
disorders [38, 41-43] and social problems.[41, 44, 45] Post-traumatic stress disorder (PTSD) 
prevalence is 33–50% among patients in SUD treatment,[46] and elevated among those with 
opioid dependence.[47, 48]  
Unfortunately, adjuncts to MAT such as counseling have failed to show improvement in 
outcomes over standard medical management alone.[49, 50] Poor treatment outcomes in this 
population are associated with the high prevalence of drug [38, 51-53] and alcohol use [39, 
40] during treatment, psychopathology,[42, 54] and chronic pain.[45, 55, 56] The need for 
behavioral strategies as adjunctive treatment support for this population to address the high 
levels of psychological and physical distress and pain management is well-recognized.[37, 42, 
56-59] However, to our knowledge, only one prior mind-body intervention, a pilot study of 
neurofeedback training, has been implemented as an adjunct to MAT for individuals with 
OUD;[60] results were promising, showing reduced opioid craving, depression, physical 
symptoms, and overall mental health distress. This study did not examine substance use 
outcomes other than craving, highlighting the need for more research like the proposed 
project to examine the potential benefit of adjunctive mind-body approaches to reduce 
substance use and prevent relapse among individuals in MAT for OUD.  
Mind-body approaches have a high level of perceived effectiveness by OUD patients in 
MAT.[61] Notably, manual and mind-body approaches were the most sought-after treatments 
among MAT patients with chronic pain[62] and have been identified as viable adjunctive 
treatments needing research for individuals on MAT for OUD.[63] Two recent large RCT 
studies of mindfulness-based interventions for the treatment of chronic pain demonstrated 
reductions in pain in the experimental vs. control groups.[64, 65] Likewise, a pilot study of a 
mindfulness-based intervention for individuals using opioids for pain (but not in treatment for 
an OUD)[66] showed reductions in pain severity, pain interference, and opioid craving 
compared to an active control. Together these studies highlight the potential promise of a 
mindfulness-based approach such as MABT, the proposed intervention for this project, for this 
unique population.  
Interoceptive Awareness and Substance Use. Interoception involves the processing of 
sensory input from inside the body[67] and interoceptive awareness involves the development 
of sensory and emotional awareness that is integral to sense-of-self and related regulatory 
processes.[65, 68] The neural mechanisms that underlie successful SUD treatment are not yet 
well understood however sensory information gained through interoception appears to play an 
important role in affective and regulatory behavior and successful inhibition of drug use. The 
role of interoception in addiction is emphasized in recent cognitive neuroscience models.[69-
72] suggesting the neurobiology that may underlie interoception and influence craving, 
reward, impulse control and overall self-awareness among substance users.[71, 73, 74] A 
review of brain imaging studies supports interoceptive models for SUD, showing significantly 
altered regulatory processes involved in interoception among those with drug dependence 
relative to those without.[71] Specifically, individuals with SUD show greater activation to 

 
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drug cues within brain regions that predict relapse vulnerability.[75-77] In SUD, attention to 
sensory experience appears to be overly attuned substance-related stimuli, to the detriment 
of broader affective processing. The capacity to attend to interoceptive experience is 
important for the evaluation and control of visceral responses to sensory events that 
ultimately motivate human behavior.[73] Importantly, while unconscious interoceptive signals 
may motivate drug-seeking behavior,[71] interoceptive awareness is thought to reveal and de-
automate such conditioning, supporting positive decision making processes critical for relapse 
prevention.[71]  
There is compelling evidence across multiple disciplines that interoception is integral to self-
regulation, including regulation of emotions and behavior.[78] Greater accuracy of 
interoceptive self-representation promotes adaptive responses, whereas dissociation from 
accurate representation can lead to dysregulation. Accordingly, addiction appears to involve 
interoceptive dysfunction, as do many other health problems that notably are often comorbid 
with addiction,[79] such as chronic pain,[80] and post-traumatic stress disorder (PTSD).[81] 
Given the high prevalence of relapse and poor retention in MAT treatment,[31] and the 
identified relapse risk factors such as stress, pain, negative affect and poor emotion 
regulation in SUD treatment,[75, 82] it is critical to identify interventions that promote 
interoceptive awareness to reduce relapse in individuals with OUD in MAT. The study of 
adjunctive interventions for cultivating interoceptive awareness to enhance treatment 
outcomes is an identified next step for SUD research.[71, 74]  
Rationale for MABT as an Adjunct to MAT of OUD. Dr. Price’s research focuses on an 
intervention, Mindful Awareness in Body-oriented Therapy (MABT), designed to teach 
interoceptive awareness. Findings from this program of research (including prior R21DA024771 
and ongoing R01DA033324) highlight the role of improving interoceptive awareness through 
MABT to reduce substance use and improve health outcomes. This research indicates that 
avoidance of body sensations (emotional or physical) is common among individuals in SUD 
treatment.[83-85] In addition, maintaining attention to one’s body sensations often exceeds 
these individuals’ perceived capacities. Dr. Price’s SUD research to date has focused on MABT 
as an adjunct to abstinence-based treatment for individuals using various primary substances 
(i.e., alcohol, amphetamines, opioids, etc.). Thus the proposed study patient characteristics 
and MAT program/setting are distinctly different from the sample and program/setting in 
prior MABT SUD studies (NIDA-funded R21 and R01). While psychiatric comorbidity is expected 
to be similar among past MABT study samples and the proposed study sample, co-morbid 
chronic pain is expected to be highly prevalent which it was not in prior SUD MABT studies. 
Likewise, the setting/treatment programs are distinctly different, involving regular visits to a 
medical setting for medication-assisted treatment but without the group psychoeducational 
program that defines intensive outpatient abstinence-based treatment. Also, while the results 
from a pilot study of Mindful Awareness in Body-oriented Therapy (MABT) for veterans with 
PTSD and comorbid chronic pain,[86] demonstrated the acceptability of MABT for chronic pain 
patients and the perceived positive impact on pain management, the study was not 
sufficiently powered to see changes on health outcomes. This proposal thus represents a next 
step in Dr. Price’s research program to examine MABT specifically for individuals in office-
based medication-assisted treatment for OUD, aligning with Stage II research to study for 

 
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whom and in what contexts this intervention may be beneficial;[87] this would be the first 
MABT SUD study to include men and the first MABT study sufficiently powered to examine the 
effect of MABT on individuals with comorbid chronic pain.  
2.2 
Study Rationale 
Mindful Awareness in Body-oriented Therapy as an Adjunct to SUD Treatment. Prior NIDA-
funded studies of MABT for SUD treatment provide an empirical basis for the design and 
methods of the current proposal. The results of prior study (R21) comparing MABT+TAU to 
TAU only (N = 46) and results from recently completed study (R01) of MABT comparing 
MABT+TAU to TAU only and Women’s Health Education (to control for time and attention) (N 
= 217) in women’s SUD treatment are summarized below. Both studies used the manualized 
MABT protocol, to be implemented in the proposed study. Dr. Price’s experience developing, 
implementing, and disseminating results of previous MABT studies provide a logical and tested 
background for this research.  
MABT Implementation as an Adjunct to Community - Based SUD Treatment: MABT 
implementation as an adjunct to SUD treatment is highly acceptable to patients and staff at 
community treatment facilities.[88] Dr. Price’s R01 was implemented in three community SUD 
clinics in the Seattle area, the vast majority of participants are very low SES (85% 
unemployed, 87% on Medicaid or Medicare, and 43% highest level of education was high 
school), similar to the characteristics we expect in the proposed sample.[89].  Likewise, 
comorbid mental health distress in the R01[89] and prior R21,[85] particularly PTSD (68%) and 
depression (34% with moderate – severe symptoms), is comparable to what is expected in the 
proposed study sample (see Section 4). 
MABT Reduces Substance Use Outcomes: MABT SUD treatment research (R21 study) showed 
significant reduction in substance use for MABT+TAU as measured by the percent days 
abstinent (primary outcome) on the Time Line Follow-Back Interview (TLFB) compared to TAU 
only.[85]  R01 findings (N =187) show significant reductions in the percent days abstinent (also 
using the TLFB as primary outcome) in MABT+TAU compared to TAU only at 6 month and 12 
month follow-up.[90]  
MABT Reduces Psychological Symptoms and Improves Emotional Well-being, Mindfulness, and 
Interoceptive Skills: MABT SUD treatment research (R21 study) showed promising results with 
significant between-group differences with moderate to large effects on mental health 
outcomes between MABT+TAU compared to TAU at 9 months. These included depression 
symptoms, eating disorder symptoms, perceived stress, dissociation, and physical symptom 
frequency.[85]  The R01 pre-post findings (N = 187) showed significant improvements for 
MABT compared to TAU in craving, depression among those that received the full intervention 
dose, improved emotion regulation (self-report and psychophysiology), interoceptive 
awareness, and mindfulness skills among the MABT completers.[89].  Longitudinal outcomes 
showed maintained improvements for MABT vs. TAU on craving, psychophysiology (well-
being/regulation), interoceptive awareness and mindfulness skills.[90] The proposed study 
examines many of the same mental health and process variables as in the above studies.  
Patients on MAT frequently suffer from chronic pain, which is a risk factor for opiate craving 

 
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and potential relapse. We conducted a cross-sectional study (K23DA027367) of 106 adults who 
were maintained on buprenorphine or methadone.[91] The primary outcome was cold pain 
tolerance assessed by cold-pressor test. Chronic pain was highly prevalent (67%), and current 
pain was even moreso (83%).  These results reinforced that pain and hyperalgesia are common 
problems in this population of persons who were maintained on MAT for treatment of OUD. In 
a subsequent study performing secondary analysis on data from the same sample, we 
examined relationships between pain and opioid craving and opioid use as measured by urine 
drug testing (UDT).[92] We found that 51% reported craving opioids in the past week, and 16% 
had a positive UDT for opiates. We concluded that chronic pain with associated opioid craving 
potentially places this population at risk for relapse. Results from these two studies 
underscore that there is an unmet need for interventions to address pain among persons on 
MAT in order to prevent relapse and improve addiction treatment outcomes.  
In summary, these preliminary studies demonstrate that MABT reduces substance use and 
comorbid mental health distress among women in abstinence-based SUD outpatient 
treatment, suggest that the MABT intervention can restore interoceptive function in the face 
of SUD, and point to the importance of addressing chronic pain in MAT for OUD. However, 
MABT has not yet been examined as an adjunct to MAT with an exclusively OUD sample nor 
have MABT studies included targeted pain outcomes, crucial to address the need for 
nonpharmacological supports for MAT treatment during this opioid epidemic. Furthermore, 
MABT has not been studied in a more generalized sample of women and men. This study is 
designed to accomplish these critical next steps. 
Mindful Awareness in Body-Oriented Therapy. The MABT protocol and training manual 
teaches interoceptive awareness and self-care skills for emotion regulation to facilitate 
improved health outcomes (see Explanatory Model, Figure 1 below).  
Figure 1. MABT Explanatory Model  
Content 
Key Processes 
Outcomes 
Body Literacy 
 
Interoceptive Training 
 
Mindful Body Awareness 
Interoceptive Awareness and  
Mindfulness Skills 
 
Interoceptive Skills for Self-
Care Integrated into Daily Life 
Substance Use and Craving 
 
Mental Health Distress/Symptoms 
 
Emotional Well-being 
 
Pain Severity and Interference 
 
MABT involves delivery of eight 75-minute one-on-one sessions, once per week. MABT is 
distinctive in its explicit focus on the development of interoceptive awareness skills for 
emotion regulation. Strategies for addressing interoceptive dysfunction are not well 
developed in typical group mindfulness-based approaches of individual psychoeducational 
approaches that include a somatic focus. To address this issue, MABT provides an 
individualized protocol for scaffolding interoceptive awareness in the face of baseline 

 
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difficulty in attending to interoceptive signals, through a combination of psychoeducational 
and somatic approaches explicitly addressing difficulties with interoceptive processing. Used 
in multiple clinical trials,[83, 85, 86, 93-95] the protocol has an incremental approach for 
teaching interoceptive awareness to facilitate development of interoceptive awareness skills 
(see Table 2). 
Table 2. Key MABT Elements (number of minutes each session)  
Stage 1 (Sessions 1- 2) 
Stage 2 (sessions 3-4) 
Stage 3 (sessions 5-8) 
Check-in (20) 
Check-in (20) 
Check-in (20) 
 Massage/Body Literacy (40)  Massage/Body Literacy (10) 
Massage/ Body Literacy (10) 
 
Interoceptive Training (30) 
Mindful Body Awareness (30) 
Session Review (15) 
Session Review (15) 
Session Review (15) 
Homework 
Homework 
Homework 
 
The MABT intervention is designed to increase self-awareness and thus participants sometimes 
experience discomfort, emotions, as well as insight. Overall MABT is very low risk, as the 
protocol is designed to be individualized to ensure safety and comfort of the participant.  To 
date, here have been no serious adverse events associated with any MABT study.   
For participants initially assigned to MABT who report continued use of opiates or other 
substances at 6 months, an additional 6 MABT sessions will be offered.  
3. STUDY DESIGN 
Design Overview: A two-group (n = 165/165), randomized, repeated measures design will be 
employed. Three hundred thirty individuals with OUD engaged in medication treatment will 
be recruited at one of five outpatient treatment sites: Harborview Medical Center, Country 
Doctor Community Health Centers, North Olympic Healthcare Network, Cascade Medical 
Advantage, and Evergreen Treatment Services. Enrolled patients will be individually 
randomized within sites to receive MABT+TAU (experimental group), or TAU alone (control). 
Assessments will be administered at baseline, post-intervention (3 months from baseline), and 
at 6, 9 and 12 months follow-up. An additional six sessions of MABT will be offered to those 
randomized to MABT who have continued substance use at six months. 
Randomization: Following baseline data collection, participants will be randomized to 
treatment group by the Research Coordinator. Dr. Pike, the project statistician, provided a 
randomization program programmed in Microsoft BASIC. Randomization will be specific to 
each study site and stratified by sex (approximately equal numbers of men and women 
assigned to each study group at each site) and baseline self-reported chronic pain.  The 
algorithm used for randomization is a modification of a minimization method[96] based on an 
overall imbalance score which measures how far out of balance (within strata) the study is for 
a given set of random assignments.  Participants will be informed of their assignment within 
one week of the initial appointment. Prior MABT studies showed no loss due to randomization 
to treatment group, thus we do not expect randomization to precipitate significant attrition. 
The Research Coordinator at each facility will not be blind to condition and will inform 
participants of their treatment condition and MABT therapist. 

 
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Measures: The outcome measures are described below (see also Table 1 in Précis). 
Primary Objectives: The primary outcome is patient-reported days of illicit opioid use. Self-
reported substance use is the recommended approach for intervention studies.[97] Days of 
illicit opioid use is defined as the number of reported days of use in last 90 days (baseline 
assessment) or since and including the last assessment date (follow-up assessments) in which 
opioids other than MAT (buprenorphine or methadone) are reported. 
Time-Line Follow-Back Interview (TLFB)[3, 4] will be used to assess opioid use, other illicit 
drugs, and commonly abused prescription medications. Participants will be asked first to 
identify what substances were used. The participant will then be asked to use a calendar to 
retrospectively estimate their substance use, for each of the identified substances. The TLFB 
method was determined for alcohol, amphetamines, cannabis, cocaine, hallucinogens, 
opiates, sedative-hypnotics, and any psychoactive substance for time periods of 0-30 days, 0-
90 days, and 0-365 days, the correlations for all substances and for the three time periods 
ranged from .73 to .95, demonstrating test-retest reliability and validity.[98]  
The secondary outcome is days of other illicit substance use is defined as the number of days 
since last assessment in which cocaine, amphetamine/methamphetamine, hallucinogens, non-
prescribed benzodiazepines or barbiturates, or alcohol heavy drinking days are reported using 
the TLFB. We will not include cannabis in this primary outcome measure due to its legal 
status in Washington State.  
Secondary Objective Outcomes: measures of mental health (distress symptoms and emotional 
well-being) will include three well-validated scales for diagnostic screening: the 9-item PHQ-9 
to screen for depression, the 7-item ( =.92) GAD-7 for anxiety[8], and the Posttraumatic 
Stress Disorder Checklist for DSM-5 (PCL-5),[9] which assesses symptoms of post-traumatic 
stress on a Likert-type scale with 20 items ( =.94). The 4th measure, the Difficulty in Emotion 
Regulation Scale short form (DERS-SF)[10, 99] assesses difficulties in the modulation of 
emotional arousal. There are 18 items on a Likert-type scale (DERS  =.93; DERS short form  
ranges from .78 to .91 with original DERS subscales) and four subscales that assess the degree 
of awareness, understanding, and acceptance of emotions, and the ability to act in desired 
ways regardless of the emotional state. The 5th and 6th measures, the Freiberg Mindfulness 
Questionnaire (FMQ) with 14 items[14], and the Multidimensional Assessment of Interoceptive 
Awareness (MAIA)[15] with 32 items on a Likert-type scale, are used to assess skills learned in 
the intervention.    
Physical symptoms will be assessed using the Medical Symptoms Checklist (MSC) and pain 
severity and interference using the Brief Pain Inventory (BPI).  The MSC measures the 
frequency (0-8 scale) and severity (0-10 scale) of 29 common physical symptoms.[19] The BPI 
is a validated, widely used measurement tool for assessing clinical pain. In the U.S. it has 
been validated in non-cancer patients with pain[18] and HIV-infected patients.[100] The 
assessment includes 13 questions which provide information on pain severity and pain 
interference in the past week. Participants are initially asked if they have experienced any 
significant pain in the past week, and if they respond positively they answer subsequent 

 
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questions about duration of pain, pain severity and interference. Pain severity is rated from 0 
(“no pain”) to 10 (“worst pain imaginable”), and participants are asked to rate their current 
pain as well as pain at its worst, at its best, and on average in the past week. Pain 
interference includes information on the impact of pain on general activity, walking, work, 
mood, enjoyment of life, relations with others, and sleep, asking the participant to rate 
interference on a scale from 0 (“does not interfere”) to 10 (“completely interferes”), and is 
reported as the mean of seven questions. Participants who responded that they had no pain in 
the past week will be coded “0” for pain severity and interference. The BPI will be 
supplemented with a single question on duration of currently reported pain in order to 
establish whether the pain is acute or chronic. 
Opioid craving will be assessed using a single item numeric scale.[5] Participants are asked: 
“On a scale of 0–10, please indicate how much craving you have experienced during the past 
week,” with responses anchored at “0=no craving at all” and “10-strongest craving ever”. 
Retention will be defined as days retained in the program, or time to program discharge. 
Program discharges are documented in the electronic medical record (EMR) and date of 
discharge will be extracted from the record. 
R01-Specific Objective 3 Outcomes: Exploration of the effectiveness of additional MABT dose 
offered at 6 months to those with continued substance use compared to those with continued 
substance use at 6 months in the TAU will be assessed using the Time-Line Follow-Back 
Interview (TLFB)[3, 4] self-reported substance use as described in in the primary objective.  
For description of the intervention, see Section 2.2. 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS  
Study Population: We plan to enroll 330 patients entering treatment for OUD at the three 
identified clinical sites. We expect the clinical characteristics of study subjects to be similar 
to those in enrolled in the SAMHSA MAT-PDOA project (see Table 3).[101] The patients at the 
two clinics have near equivalence in the numbers of men and women served, and age range 
(18 - 70 years old) with the majority (59%) under the age of 35. Most patients are white, low-
income, have at most a high school education, and are on public insurance (Medicare or 
Medicaid), with substantial mental health and substance use co-morbidity. Approximately 25% 
are minorities.  
Table 3. Description of Enrolled Patients in 
WA-MAT-PDOA Program (n=400) 
Male  
55% 
Age, Mean  
36.9 
White, Non-Hispanic 
78% 
Mod-Severe Depression (PHQ9>10) 
67% 
Mod-Severe Anxiety (GAD7>10) 
62% 
Mod-Severe PTSD (PCL>29) 
56% 

 
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Past 30-Day: 
 
Cannabis Use 
37% 
Alcohol Use 
22% 
Opioid Use 
70% 
     Illicit Rx Opioid Use 
39% 
     Heroin Use 
47% 
Injection Drug Use 
31% 
Employed or Student 
31% 
Housed 
91% 
Criminal Involvement* 
12% 
*Arrests, Probation/Parole, Jailed, Sentencing 
 
4.1 
Inclusion Criteria 
 
Candidates for participation must meet all of the following criteria to participate in the 
study.  Participants must be: 1) diagnosed with OUD, 2) enrolled in a medication treatment 
program for opioid use disorder, 3) over 18 years old, 4) enrolled and is stable in program 
involving (to assure medication initiation/induction has occurred) involving (if on 
buprenorphine) at least 4 weeks of treatment (to assure medication  initiation/induction has 
occurred) and Rx appointments are less frequent than once/week, and (if on methadone) at 
least 90 days in treatment with a minimum dose of 60mg, no missed dose evaluation 
appointments in past 30 days, and no more than 3 missed doses in 30 days, 5) willing to 
forego (non-study) manual (e.g., massage) and/or mind-body therapies (e.g., mindfulness 
meditation) for 3 months (baseline to post-test); 6) willing to sign release for access of 
electronic medical records; 7) fluent in English; 8) able to attend study sessions when 
offered.  
4.2 
Exclusion Criteria 
Candidates meeting any of the following criteria at baseline will be excluded from study 
participation.  Participants must not be: 1) unwilling or unable to remain in medication 
treatment for OUD for the duration of the trial (includes planned relocation, pending 
incarceration, planned surgical procedures, etc.); 2) over 24 weeks gestation or unknown 
gestation, if pregnant; 3) noted by clinical or study staff as showing overt psychosis or other 
conditions such as cognitive impairment; cognitive impairment to be assessed with an 
adapted 7-item Mini-Mental Status Exam (MMSE),[102] a common screening tool in SUD 
treatment studies,[103] if there is questionable difficulty comprehending the consent. 
4.3 
Study Enrollment Procedures  
Recruitment: Patients enrolling in MAT at the study sites will be recruited for study 
participation. Flyers with information about the trial will be distributed to clinicians and staff 
working with patients in medication treatment for OUD. The Nurse Care Manager(s) or 

 
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Providers at each site, who see patients in the program on a weekly basis at the start of 
treatment, will identify patients who meeting basic eligibility criteria, and will distribute the 
recruitment flyer to these participants at the time of their visit while also providing the 
patient with a brief overall study description and an opportunity to ask questions.  
The flyer will explain that study participation involves randomization to one of two study 
conditions, and that one of these conditions involves receiving an 8 session intervention with 
a focus on body awareness, mindfulness skills, and self-care. Patients interested in study 
participation will be asked by the clinical staff to for permission to be contacted by the 
Research Coordinator (RC). The clinical staff will provide the RC with documentation with 
each referral that the patient meets basic eligibility criteria for study involvement (e.g. 
diagnosed with OUD and stable on medication dose). Based on prior intervention study 
experience at community SUD treatment facilities and the pilot for this study, we expect to 
recruit 8-12 participants per month across the sites. This recruitment rate would allow us to 
complete recruitment within the projected timeline. Assignment to study groups will involve 
stratification by sex and chronic pain (approximately equal numbers at each site) to ensure 
parity between men and women, and to ensure an equal distribution by group on chronic 
pain.  
Screening: The Research Coordinator (RC) at each site will screen interested patients for 
eligibility in-person at the time of referral (if available) or by phone using a standardized 
screening script that includes acquiring verbal consent to collect preliminary screening data.  
On conclusion, the results of screening interview (eligibility based on inclusion/exclusion 
criteria, election of participation) will be entered into the screening log of the study 
database.  Candidates who are eligible and willing to continue will be scheduled for an initial 
assessment visit within 14 days of the screening.   
Consent and Enrollment:  The initial scheduled in-person visit includes the informed consent 
process during which candidates will be asked to read the consent form (or if preferred, have 
it read to them), after which the RC will verbally reaffirm major points (participation is 
voluntary, potential risks, randomization protocol, etc.) and elicit and answer any questions 
from the candidate.  If the candidate provides written consent, then the enrollment process 
will continue with the baseline data collection.  Upon completion of the initial assessment, 
participants will be enrolled in the study.  If at any time during this process the candidate 
withdraws prior to enrollment, disposition and reason for withdrawal (if obtainable) will be 
documented in the screening log. 
Randomization: Following baseline data collection, participants will be randomized to 
treatment group. Dr. Pike, the project statistician, provided a randomization program 
programmed in Microsoft BASIC. Randomization will be specific to each study site and 
stratified by sex (approximately equal numbers of men and women assigned to each study 
group at each site) and baseline self-reported chronic pain.  The algorithm used for 
randomization is a modification of a minimization method[96] based on an overall imbalance 
score which measures how far out of balance (within strata) the study is for a given set of 
random assignments.  Dr. Pike, who will have no contact with study participants, programmed 

 
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the site-specific random assignment generators so that assignments become known to the 
Research Coordinator only upon entry of the eligibility data. Prior MABT studies showed no 
loss due to randomization to treatment group, thus we do not expect randomization to 
precipitate significant attrition. The Research Coordinator at each facility will not be blind to 
condition and will inform participants of their treatment condition and MABT therapist. 
5. STUDY INTERVENTIONS  
5.1 
Interventions, Administration, and Duration  
The intervention in this study is Mindful Awareness in Body-oriented Therapy (MABT), 
administered one-on-one by therapists trained in the MABT protocol at the outpatient 
treatment site where the participant was recruited from and receives their MAT care.  
Individuals in the MABT intervention group will receive 8 weekly 1.25 hour one-on-one 
sessions of MABT between baseline and the 3 month follow-up assessment.  There are no 
restrictions to supportive care, medications, or other treatments which intervention group 
participants may use during their participation in the study with the exception of additional 
manual (e.g., massage) and/or mind-body therapies of meditation and yoga during the first 
three months of study engagement (this information is part of the screening process for 
enrollment, and will be reiterated by the research coordinator at the time of study 
enrollment). There are no anticipated adverse effects of the intervention other than the 
possibility of short-term emotional discomfort.  
At six months, those in the MABT treatment group with continued substance use will be 
offered an additional six sessions of MABT between the 6 month and 9 month assessments.   
5.2 
Handling of Study Interventions  
Mindful Awareness in Body-oriented Therapy (MABT): The MABT intervention has a well-
developed protocol and training manual for research. Used in multiple clinical trials,[83, 85, 
86, 93-95] the protocol has an incremental approach for teaching interoceptive awareness 
skills and developing weekly individualized homework based on session content to promote 
integration of practice into daily life. Individuals in the MABT treatment group will receive 8 
weekly 1.25 hour one-on-one sessions of MABT. Research therapists will be hired and trained 
to provide the MABT intervention.  MABT has three distinct stages (see Table 2). Stage 1 
(sessions 1–2), develops body literacy, the ability to identify and articulate sensory 
awareness. Body literacy training is done in the context of massage therapy to facilitate 
sensory awareness related to attention to the quality of soft tissue (e.g., muscular tension). 
Stage 2 (sessions 3–4) focus on interoceptive awareness training to develop the ability to 
access inner body awareness and begin to make links between physical and emotional 
sensations. Stage 3 (sessions 5–8) focuses on the development and practice of mindful body 
awareness involving sustained interoceptive attention which facilitates positive shifts in 
sensory experience as well as insights that motivate behavior change. Each session begins 
with a semi-structured check-in to build trust and familiarity between therapist and 
participant, and ends with session review to facilitate cognitive integration of the session 

 
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material and to collaboratively develop the homework for the interim week. The 
interoceptive training components (stages 1–3) are designed with an incremental approach to 
facilitate learning, particularly important for individuals with SUD who often have difficulties 
attending to sensory (physical and emotional) awareness. Individualized homework is based 
on session content and crafted to promote integration of practice into daily life.   
The additional six MABT sessions that will be offered to eligible participants at 6 months will 
be delivered as explained above and will include all stages of the intervention as outlined in 
Table 2 but will be individualized to address the intervention components needing the most 
review (if the participant did not complete MABT initially) or will follow the intervention 
protocol for delivery of the first 6 of 8 sessions if the received no prior MABT sessions when 
initially assigned. 
A single therapist works with each study participant for MABT delivery.  In case of illness or 
vacation, on the part of either participant or interventionist, the intervention period allows 
for approximately 12 weeks to deliver an 8 week intervention. Any longer-term breaks needed 
in interventionist coverage/ staff turnover will be handled by having a trained therapist ready 
to step-in if needed, either to provide temporary coverage (i.e. to work with one set of 3-4 
participants over 2-3 months to deliver a full set of MABT sessions) or to join the research 
team more permanently.   
Treatment As Usual: All participants will continue to receive usual outpatient treatment at 
the site from which they were recruited. The outpatient programs at these sites are 
comparable; they offer medication treatment provided by a Medical Provider or through a 
Nurse Care Manager (NCM) model adapted from the Massachusetts Model as piloted in the 
MAT-PDOA program. The model uses Nurse Care Managers (NCM) as the hub of the medical 
care team to coordinate and manage patients. The use of the NCM addresses many barriers to 
medication  prescribing that physicians face. For example, treatment for opioid use disorders 
with buprenorphine/naloxone (BUP/NX) is time-intensive in the first 2-3 months. Clinical 
steps which the NCM assists include: an initial screening for the appropriateness of BUP/NX; a 
comprehensive assessment of substance use and consequences, medical and mental health, 
and current barriers to and supports for recovery; review for formal diagnosis of opioid use 
disorder and appropriateness for MAT; scheduling and monitoring of the induction (i.e., 
initiation of BUP/NX which must be accomplished while patients are in withdrawal), followed 
by weekly visits for prescriptions, and urine drug testing for the first 1-2 months (less 
frequent thereafter if patients are abstaining). Frequent team meetings with the physician, 
NCM and program manager occur, during which team members can monitor progress and 
update treatment plans together. Counseling is available for all patients, but not required.  
5.3 
Concomitant Interventions  
5.3.1 Allowed Interventions 
Participants will all be enrolled in MAT for the duration of the study. Participants are 
welcome to engage in optional counseling or attend peer support meetings such as 12-step 
groups, as this is considered part of treatment as usual (TAU).  If a participant withdraws 

 
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from MAT during the study, we will continue to follow them (per intent to treat); in all cases, 
we will collect information on any related treatment activities engaged in during the study 
period.   
5.3.2 Required Interventions 
The participants must have received their fourth weekly MAT prescription to be enrolled in 
the study.  Per intent-to-treat design, study participation is not contingent on continued 
adherence to MAT treatment once enrolled in the study.  
5.3.3 Prohibited Interventions 
There are no restrictions to supportive care, medications, or other treatments which 
participants may use during their participation in the study with the exception of additional 
manual (e.g., massage) and mind-body therapies (specifically yoga and meditation) from 
baseline to 3 months.  To assess whether participants adhere to this exclusion, or utilize 
these therapies later in the study, participants will asked about their receipt of massage or 
participation in any yoga or meditation classes at each assessment.  
5.4 
Adherence Assessment  
To assess adherence to the study intervention we will record number of sessions attended. In 
addition to an intent-to-treat analysis, we will also examine MABT dose.  Specifically, we will 
examine outcomes for participants who attended > 75% of the initial intervention sessions 
(i.e. 6-8 sessions) between baseline and 3 months, as this is the number of sessions needed in 
order to receive all intervention components, compared to TAU.  We will also record the 
number of additional sessions received by eligible participants between 6 and 9 months. 
6. STUDY PROCEDURES  
6.1 
Table 4. Schedule of Evaluations  
Assessment 
Screening: Visit or Call 
(Day-14 to Day -1) 
Baseline, Enrollment, 
Randomization: Visit 1  
(Day 0) 
Treatment Visit 1 (W1) 
Treatment Visit 2-8 
 (W2 - 11) 
Followup1: Post- 
Treatment Visit (W12) 
Followup2: Visit (W24) 
Booster Treatment 
 Visits 1-6 (W25 - 38) 
Followup2: Visit (W39) 
Followup2: Visit (W52) 
Screening Questions 
X 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
Informed Consent Form   
 
X 
 
 
 
 
 
 
 
Demographics and Health History 
 
X 
 
 
 
 
 
 
 
Trauma History (TLEQ) 
 
X 
 
 
 
 
 
 
 
REDCap Survey 
 
X 
 
 
X 
X 
 
X 
X 
Treatment Adherence (Retention to 
MAT)  
 
 
 
 
 
X 
 
 
X 

 
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Assessment 
Screening: Visit or Call 
(Day-14 to Day -1) 
Baseline, Enrollment, 
Randomization: Visit 1  
(Day 0) 
Treatment Visit 1 (W1) 
Treatment Visit 2-8 
 (W2 - 11) 
Followup1: Post- 
Treatment Visit (W12) 
Followup2: Visit (W24) 
Booster Treatment 
 Visits 1-6 (W25 - 38) 
Followup2: Visit (W39) 
Followup2: Visit (W52) 
Economic Indicators (Employment, 
Health Utilization, Legal Status) 
 
X 
 
 
X 
X 
 
X 
X 
Toxicology screen  
 
X 
 
 
 
 
 
 
 
Enrollment/Randomization 
 
X 
 
 
X 
X 
 
X 
X 
MABT Process Evaluation 
 
 
X 
X 
 
 
X 
 
 
Adverse Events  
 
 
X 
X 
X 
X 
X 
X 
X 
6.2 
Description of Evaluations  
6.2.1 Screening Evaluation 
Consenting Procedure 
The Research Coordinator (RC) at each site will acquire verbal consent to ask screening 
questions to determine eligibility prior to beginning screening procedures.  Written consent 
will be obtained for all further study procedures as described in section 6.2.2. 
Screening 
After acquiring consent to screen, the RC at each site will screen interested patients to 
determine eligibility in-person at the time of referral (if available) or by phone using a 
standardized screening script.  On conclusion, the results of screening interview will be 
entered into the screening log of the study database.  Results are 1) eligibility based on 
inclusion/exclusion criteria, 2) if eligible, election of participation (if no, reason why not), 3) 
if not eligible, reason for ineligibility.  Candidates who are eligible and willing to continue 
will be scheduled for the consent /initial assessment visit within 14 days of the screening, or 
be rescreened prior to progressing.  Eligibility, election, and follow-up information (for those 
who are eligible and willing to continue) will be entered in the study database. 
6.2.2 Enrollment, Baseline, and/or Randomization 
Enrollment 
The first study visit will begin with the consent process. At the consent visit, the RC will ask if 
the candidate would like to read it themselves or have it read to them, then will give the 
participant time to read the consent (or read it aloud).  Then the RC will paraphrase each 
section of the consent form, and encourage the candidate to ask questions.  If the candidate 
wishes to proceed, they will sign and date the consent form.  If there is any concern about 
comprehension, the RC will administer an adapted 7-item Mini-Mental Status Exam to ensure 
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The RC will also explain the HIPAA and Medical Records Release forms (if required by the 
clinical site) to acquire limited data elements from the candidate’s medical record.  
Permission to access medical records is required for participation in the research study.  A 
copy of the forms will be provided to the candidate.  A locator form with additional contact 
information will also be requested, but refusal does not preclude participation in the study. 
After informed consent is given, the baseline assessment is completed. On completion of the 
baseline assessment, the participant will be enrolled and randomized. 
Completion status for the consent procedures will be entered in the study database, and 
signed forms filed in the candidate’s name file in a locked filing cabinet, separate from 
numerical identifiers. 
Baseline Assessments 
The baseline assessment requires the participant to complete: 1) the Timeline Follow-back 
Interview to report on substance use over the past 90 days, 2) an online survey (REDcap) to 
collect a set of baseline-only questionnaires specific to demographics and health history, 3) 
an online survey using REDcap that collect responses to self-report outcome measures, 4) a 
toxicology screen involving a urine sample for biochemical evaluation. The administration of 
the baseline assessment is process takes approximately 1 hour. All assessments will be 
delivered in a standardized order as outlined below; at baseline only, there are two 
additional measures on the online REDcap survey 
Should a participant be unable to provide data during the scheduled assessment (e.g., unable 
to provide a urine sample, or unable to complete the assessment in one sitting), research 
coordinators have up to 14 days to complete the data collection for the assessment. 
Baseline, Enrollment, Randomization: Visit 1 (Day 0) 
Measures:  
Primary outcome: 
• 
Time-Line Follow-Back Interview (TLFB)[3, 4] will be used to assess self-reported 
opioid use, and use of other illicit drugs, marijuana and alcohol use.  
Demographics and health history: 
• 
Health History Form is based on the Addiction Severity Index.[1]  
• 
Trauma Life Events Questionnaire (TLEQ)[2] will be used to describe lifetime trauma 
exposure. 
Secondary outcomes:  
• 
The PHQ-9 will be used to measure depression symptoms.[6, 7]. 
• 
The GAD-7 will be used to measure anxiety symptoms.[8]  
• 
Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5),[9] assesses symptoms of 
post-traumatic stress on a Likert-type scale. 

 
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• 
Difficulty in Emotion Regulation Scale – short form (DERS- SF)[10] assesses difficulties 
in the modulation of emotional arousal.  
• 
Opioid craving will be assessed using a single item numeric scale.[5] Participants are 
asked: “On a scale of 0–10, please indicate how much craving you have experienced 
during the past week,” with responses anchored at “0=no craving at all” and “10-
strongest craving ever”.  
• 
Freiberg Mindfulness Questionnaire has 14 items to assess skills learned in the 
intervention.[14] 
• 
Multidimensional Assessment of Interoceptive Awareness (MAIA)[15] has 32 items on a 
Likert-type scale to assess skills learned in the intervention.  
• 
Brief Pain Inventory (BPI) is a validated, widely used measurement tool for assessing 
clinical pain.[18] The BPI will be supplemented with a single question on duration of 
currently reported pain in order to establish whether the pain is acute or chronic. 
• 
Medical Symptoms Checklist will assess self-report of physical symptoms.[19] 
Descriptive Data: 
• 
Economic Indicators questions will gather data on employment, health utilization, and 
legal status. 
• 
Toxicology screen will be used to collect point prevalence for substance use on at each 
assessment time point, and will serve as supplemental data for validation of the TLFB 
results.  
After the completion of the baseline assessment, the participant is formally enrolled in the 
study. 
Randomization  
Following baseline data collection, participants will be randomized to treatment group by the 
Research Coordinator.  Randomization will be provided by the project statistician. Stratified 
randomization by study site, baseline self-reported chronic pain, and gender, will be used to 
distribute participants evenly between the two treatment conditions at each facility and 
within each gender and experience of chronic pain. Randomization will use a modified 
minimization method algorithm[96] based on an overall imbalance score which measures how 
far out of balance (within strata) the study is for a given set of random assignments to ensure 
approximately equal accrual into the two experimental arms and to facilitate concealment of 
treatment assignments.  After randomization (for those assigned to treatment group), the RC 
will contact the site interventionist to inform them of their new assigned participant to 
schedule the first intervention visit. 
6.2.3 Blinding 
The statistician will be blind to study group.  The RC at each facility will not be blind to 
condition and will inform participants of their study group condition.   

 
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6.2.4 Follow-up Visits 
Treatment 
Initial Treatment Visit 1 (W1) 
• 
Adverse Events 
• 
MABT Process Evaluation (self-report by interventionists) 
Initial Treatment Visit 2-8 (W2 - 11) 
• 
Adverse Events 
• 
MABT Process Evaluation (self-report by interventionists) 
• 
MABT Practice Log (self-reported home practice by participants for use by 
interventionists) 
Additional MABT Sessions 1-6 (W25 – W38) 
• 
Adverse Events 
• 
MABT Process Evaluation (self-report by interventionists) 
• 
MABT Practice Log (self-reported home practice by participants for use by 
interventionists) 
Assessments 
Followup1-4 Assessment Visits (W12, W24, W39)  
The follow-up assessments will be scheduled 12 weeks, 24 weeks, and 39 weeks from baseline, 
and takes approximately 45 minutes to complete.  Coordinators will make every effort to 
schedule the assessment near to the target date, but are allowed -2 weeks/+4 weeks to 
capture follow-up assessment data.  In addition to this assessment, we will also gather 
treatment retention data through electronic medical record (EMR) at the 6 and 12 month 
assessments.  
Should a participant be unable to provide data during the scheduled assessment (e.g., unable 
to provide a urine sample, or unable to complete the assessment in one sitting), research 
coordinators have up to 14 days to complete the data collection for the assessment. 
W24:  The Time-Line Follow-Back Interview (TLFB)[3, 4] results collected at 6 months will be 
used to determine those in the MABT study group with continued substance use who will be 
offered six additional MABT sessions between month 6 and 9. Criteria for eligibility for 
additional MABT sessions is 1) randomized to the MABT + TAU study group, and b) self-report 
of substance use on the TLFB, including any days of heavy alcohol drinking and excluding 
marijuana use. 
 
Primary outcome: 
• 
Time-Line Follow-Back Interview (TLFB)[3, 4] will be used to assess self-
reported opioid use, and use of other illicit drugs, marijuana, and alcohol.  
Secondary outcomes:  

 
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• 
The PHQ-9 will be used to measure depression symptoms.[6, 7]. 
• 
The GAD-7 will be used to measure anxiety symptoms.[8]  
• 
Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5),[9] assesses 
symptoms of post-traumatic stress on a Likert-type scale. 
• 
Difficulty in Emotion Regulation Scale – short form (DERS- SF)[10] assesses 
difficulties in the modulation of emotional arousal.  
• 
Opioid craving will be assessed using a single item numeric scale.[5] 
Participants are asked: “On a scale of 0–10, please indicate how much 
craving you have experienced during the past week,” with responses 
anchored at “0=no craving at all” and “10-strongest craving ever”.  
• 
Freiberg Mindfulness Questionnaire has 14 items to assess skills learned in 
the intervention.[14] 
• 
Multidimensional Assessment of Interoceptive Awareness (MAIA)[15] has 32 
items on a Likert-type scale to assess skills learned in the intervention.  
• 
Brief Pain Inventory (BPI) is a validated, widely used measurement tool for 
assessing clinical pain.[18] The BPI will be supplemented with a single 
question on duration of currently reported pain in order to establish 
whether the pain is acute or chronic. 
• 
Medical Symptoms Checklist will assess self-report of physical 
symptoms.[19] 
Descriptive Data: 
• 
Economic Indicators questions will gather data on employment, health 
utilization, and legal status. 
• 
Biochemical drug screen will be used to collect point prevalence for 
substance use on at each assessment time point, and will serve as 
supplemental data for validation of the TLFB results.  
• 
Adverse Events 
6.2.5 Completion/Final Evaluation 
Followup2: Final Visit (W24)  
The final evaluation (12 month follow-up) will be scheduled 52 weeks from baseline, and takes 
approximately 45 minutes to complete.  Coordinators will make every effort to schedule the 
assessment near to the target date, but are allowed -2 weeks/+4 weeks to capture final 
assessment data.  In addition, to this assessment, we will also gather treatment retention data 
through electronic medical record (EMR).  
 
Should a participant be unable to provide data during the scheduled assessment (e.g., unable 
to provide a urine sample, or unable to complete the assessment in one sitting), research 
coordinators have up to two weeks to complete the data collection for the assessment. 
 
If study staff learn of special circumstances that would necessitate collecting W24 data earlier 
than the allowed window of -2 weeks (e.g., expected relocation, incarceration, etc.), the 

 
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assessment will be completed early and the participant followed to determine if a repeat 
assessment within the allowable window is possible.  If so, the final assessment will be 
repeated and the later data used in the final analysis.  Participants will be remunerated for 
the second W24 assessment.  
 
Primary outcome: 
• 
Time-Line Follow-Back Interview (TLFB)[3, 4] will be used to assess self-
reported opioid use, and use of other illicit drugs, marijuana, and alcohol.  
Secondary outcomes:  
• 
The PHQ-9 will be used to measure depression symptoms.[6, 7]. 
• 
The GAD-7 will be used to measure anxiety symptoms.[8]  
• 
Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5),[9] assesses 
symptoms of post-traumatic stress on a Likert-type scale. 
• 
Difficulty in Emotion Regulation Scale – short form (DERS- SF)[10] assesses 
difficulties in the modulation of emotional arousal.  
• 
Opioid craving will be assessed using a single item numeric scale.[5] 
Participants are asked: “On a scale of 0–10, please indicate how much 
craving you have experienced during the past week,” with responses 
anchored at “0=no craving at all” and “10-strongest craving ever”.  
• 
Freiberg Mindfulness Questionnaire has 14 items to assess skills learned in 
the intervention.[14] 
• 
Multidimensional Assessment of Interoceptive Awareness (MAIA)[15] has 32 
items on a Likert-type scale to assess skills learned in the intervention.  
• 
Brief Pain Inventory (BPI) is a validated, widely used measurement tool for 
assessing clinical pain.[18] The BPI will be supplemented with a single 
question on duration of currently reported pain in order to establish 
whether the pain is acute or chronic. 
• 
Medical Symptoms Checklist will assess self-report of physical 
symptoms.[19] 
Descriptive Data: 
• 
Economic Indicators questions will gather data on employment, health 
utilization, and legal status. 
• 
Biochemical drug screen will be used to collect point prevalence for 
substance use on at each assessment time point, and will serve as 
supplemental data for validation of the TLFB results.  
• 
Adverse Events 
 

 
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Withdrawal of Participants 
MABT sessions will be discontinued for any of the following three reasons, but not withdrawn 
from study (e.g., participant will be continued to be followed for study assessments): 
1. Participants are inebriated or high from alcohol or drugs such that they are not able to 
engage in the intervention on more than one scheduled session. 
2. If, in consultation with the participant’s healthcare providers, there is concern for 
his/her safety and well-being (e.g., escalation of symptoms). 
A participant could be withdrawn from study if: 
If, in consultation with the participant’s health care providers, there is sufficient concern for 
his/her safety and well-being that the participant may be withdrawn and re-directed to more 
appropriate care. This is described to the participant in the consent process. 
If a participant chooses to formally withdraw from the study by notifying the principal 
investigator, any data collected from the participant will not be used in the analysis. 
7. SAFETY ASSESSMENTS  
7.1 
Specification of Safety Parameters 
It is possible that participants may experience anxiety related to questions asked on the 
questionnaires.  For participants who receive MABT, there may be anxiety due to the use of 
touch in the MABT sessions or the development of a new therapeutic relationship.  During the 
course of the study, interventionists may develop concerns regarding a participant’s risk of 
suicide or harm to self or others, or health concerns such as increased medical symptoms such 
as pain, or mental health symptoms of severe depression, anxiety, PTSD. Upon entering the 
study, all participants will be asked to sign a Treatment Information Release Form, which will 
allow for two-way communication between research and clinical staff to discuss concerns 
such as those described. 
Any medical emergencies, disclosed suicidal ideation, or other urgent concerns for participant 
safety experienced by the research coordinators or interventionists will be addressed 
according to the procedures at the clinical site where the participant is seen.  Review of 
these protocols and accessing emergency contact information will be included in the staff 
training for all study staff.  The study staff with the experience will report the event and 
resolution/follow-up to the principal investigator(s) that day. 
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
The pilot project for this study was found to impart minimal risk by the University of 
Washington IRB, and the protocol for the full trial will be based on the pilot study.  Few to no 

 
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study-related adverse events are expected.  Prior studies of MABT showed no serious adverse 
events.[83, 85, 86, 89, 93, 94, 104] 
7.3 
Adverse Events and Serious Adverse Events  
For this study, the following standard AE definitions are used: 
Adverse event:  An adverse event (AE) is any untoward medical occurrence in a subject 
during participation in the clinical study or with use of the experimental agent being 
studied. An adverse finding can include a sign, symptom, abnormal assessment (laboratory 
test value, vital signs, electrocardiogram finding, etc.), or any combination of these 
Serious Adverse Event:  A serious adverse event (SAE) is any AE that results in one or more 
of the following outcomes:  
•  Death  
•  A life-threatening event  
•  Inpatient hospitalization or prolongation of existing hospitalization  
•  A persistent or significant disability/incapacity  
•  A congenital anomaly or birth defect  
•  An important medical event based upon appropriate medical judgment 
AEs are graded according to the following scale: 
Mild:  An experience that does not have a major impact on the patient (e.g., is transient, 
requires no special treatment or intervention, does not generally interfere with usual daily 
activities). This includes transient laboratory test alterations. 
Moderate:  An experience that causes the patient some minor inconvenience, but is 
alleviated with simple therapeutic treatments. The experience impacts usual daily activities.  
Includes laboratory test alterations indicating injury, but without long-term risk. 
Severe:  An experience that causes a substantial disruption to the patient’s well-being (e.g., 
requires therapeutic intervention). The experience interrupts usual daily activities. If 
hospitalization (or prolongation of hospitalization) is required for treatment it becomes an 
SAE. 
The study will use a form specifically for collection of AEs.  AEs will be solicited at all 
participant followup assessment visits with the RC and collected at all intervention visits by the 
Interventionists. The AE form will have the following attribution scale: 
Not related: The AE is clearly not related to the study procedures (i.e., another cause of 
the event is most plausible and/or a clinically plausible temporal sequence is inconsistent 
with the onset of the event). 
Possibly related:  An event that follows a reasonable temporal sequence from the initiation 
of study procedures, but that could readily have been produced by a number of other 
factors. 

 
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Related: The AE is clearly related to the study procedures. 
We will follow the definition and rules for reporting for unanticipated problems as required 
by the UW IRB. An “unanticipated problem” is a problem or event that meets all of the 
following criteria: 
1) Unexpected – The harm (or potential harm) is inconsistent with risk information 
previously reviewed and approved by the IRB in terms of nature, severity, or 
frequency as well as the characteristics of the study population. 
2) Related or probably related to participation in the research. Probably related: 
There is a reasonable probability (more likely than not) that the incident, 
experience or outcome may have been caused by the procedures involved in the 
research, or that it is associated with the use of any drug, biologic, or medical 
device that is part of the research. 
3) Suggests that the research places (or could have placed) subjects or others at a greater 
risk of harm than was previously known or recognized. 
 
Unanticipated problems will be reported within the timeframe required by UW IRB (10 
business days). 
7.4 
Reporting Procedures 
AE Reporting and Follow-up 
During the post-intervention and follow-up assessments, the Research Coordinator will inquire 
about AEs and complete a participant event form (PEF) if an AE is reported. Likewise, MABT 
Interventionists will complete a PEF form if an AE is reported during check-in’s prompted in 
the intervention protocol.  PEF forms will be submitted to the project manager weekly, and 
all adverse events, with the exception of clinically insignificant events and minor common 
illnesses and injuries (e.g., cold/flu, scrapes, upset stomach, low-grade headaches) will be 
documented on an AE Log and will be reported every 2 weeks to the contact PI, who provides 
the grading and attribution evaluation.  AEs will be summarized and discussed monthly 
amongst the core research team.  AE summary reports will be provided quarterly to the 
independent monitor (IM), and to the NCCIH at the time of the annual progress report. 
Reports will provide information on cumulative incidents and if in total the events suggest 
that subjects or others are at greater risk, investigators and the IM will address whether or 
not the consent form needs to be changed.  In the annual AE summary, the Independent 
Monitor Report will state that he has reviewed all AE reports.  If an AE/SAE meets the criteria 
of unanticipated problem for the UW IRB, it will be reported within 10 business days.  Breach 
in confidentiality will reported to the IRB within 24 hours. 
SAE Reporting 
SAEs that are unanticipated, serious, and possibly related to the study intervention will be 
reported to the IM and NCCIH in accordance with requirements.  
•  Unexpected fatal or life-threatening AEs related to the intervention will be reported to 
the NCCIH Program Officer within 7 days. Other serious and unexpected AEs related to 
the intervention will be reported to the NCCIH Program Official within 15 days.  

 
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•  Anticipated or unrelated SAEs will be handled in a less urgent manner but will be 
reported to the IM and NCCIH in accordance with their requirements.  
7.5 
Follow-up for Adverse Events 
During the study, participants will be attending an outpatient treatment program for OUD 
where they can be monitored and have access to clinical staff. Thus, AEs will be managed in 
conjunction with OUD treatment program staff, with permission from the participant.  If a 
participant is no longer involved in opioid use disorder treatment, AEs will be managed by the 
research staff; however, if danger to self or others is identified, crisis intervention procedures 
will be initiated that may include referral or contacting community mental health emergency 
services.  
7.6 
Safety Monitoring  
Given the IRB-determined minimal risk and early Phase II nature of the research, there will be 
no Data Safety Monitoring Board or Independent Monitoring Committee. Independent safety 
and data oversight will be provided by the Independent Monitor (IM) James Walsh M.D., an 
independent physician and appropriate expert with relevant expertise for advising the study 
investigators. He is qualified to review the patient safety data generated by this study 
because of his unique expertise in the area of opioid use disorder treatment as the Medical 
Director of the Addiction Recovery Service in a local medical system, Swedish Medical Center. 
The IM will meet with the study team at the start of each study year to get an overview of the 
study, study implementation expectations, and study progress; and will receive quarterly 
brief reports detailing subject accrual, enrolled subject status and adherence, and AE/SAE 
summaries, and more frequent reporting by request if concerns arise.  A DSM annual summary 
report will be provided to the IM in conjunction with required annual reporting to the IRB and 
NCCIH, which will detail monthly recruitment, enrollment, and retention against milestones; 
participant adherence, AE/SAE summary, and any other safety-related study information 
(e.g., serious non-compliance).  Annual report tables will be generated only from aggregate 
(not by group assignment) baseline and aggregate safety data for the study population. 
8. INTERVENTION DISCONTINUATION  
MABT sessions will be discontinued for any of the following reasons, but participant will not 
be withdrawn from study: 
1. Participants are inebriated or high from alcohol or drugs such that they are not able to 
engage in the intervention on more than one scheduled session. 
2. If, in consultation with the participant’s healthcare providers, there is concern for 
his/her safety and well-being (e.g., escalation of symptoms). 
The participant could be withdrawn from study if, in consultation with the participant’s 
health care providers, there is sufficient concern for his/her safety and well-being that the 

 
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participant may be withdrawn and re-directed to more appropriate care. This is described to 
the participant in the consent process. 
9. STATISTICAL CONSIDERATIONS  
9.1 
General Design Issues  
Statistical Hypotheses: 
This project has one primary objective with a primary and a secondary hypothesis, and three 
secondary objectives with a single hypothesis as specified below. 
Design Overview: A two-group (n = 165/165), randomized, repeated measures design will be 
employed. Three hundred thirty individuals with OUD engaged in MAT treatment will be 
recruited at one of three outpatient treatment sites, Harborview Medical Center, Country 
Doctor Community Health Centers, and North Olympic Healthcare Network. Enrolled patients 
will be individually randomized within sites to receive MABT+TAU (experimental group), or 
TAU only (control). An additional six sessions of MABT will be offered to those randomized to 
MABT who have continued substance use at six months.  Assessments will be administered at 
baseline, post-intervention (3 months), and at 6, 9, and 12 month follow-up.   
Primary Objective: Primary hypothesis: MABT+TAU will result in significantly fewer days of 
OU compared to TAU only from baseline to to 12 months.  
The primary outcome is patient-reported days of illicit opioid use. Self-reported substance 
use is the recommended approach for intervention studies.[97] Days of illicit opioid use is 
defined as the number of days in which use of opioids other than MAT (buprenorphine or 
methadone) are reported.  The TLFB method[3, 4] was determined for alcohol, 
amphetamines, cannabis, cocaine, hallucinogens, opiates, sedative-hypnotics, and any 
psychoactive substance for time periods of 0-30 days, 0-90 days, and 0-365 days, the 
correlations for all substances and for the three time periods ranged from .73 to .95, 
demonstrating test-retest reliability and validity.[98]   
Primary Objective: Secondary hypothesis: MABT+TAU will result in significantly fewer days 
of non-opioid substance use compared to TAU only from baseline to  baseline to 12 months. 
Days of other illicit substance use is defined as the number of days of non-opioid substance 
use (.e.g. cocaine, methamphetamine, hallucinogens, non-prescribed benzodiazepines). We 
will also be reporting the number days the participant reports heavy drinking (>=5 drinks/day 
for males, and >=4 drinks per day for females).  
Secondary Objective 1 Hypothesis: MABT+ TAU will result in significantly improved mental 
health (depression, anxiety, trauma), emotion regulation, interoceptive awareness and 
mindfulness skills), and physical health distress and pain (symptoms, pain severity, pain 
interference) compared to TAU only from baseline to  6 months (R33) and baseline to 12 
months (R01). 

 
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Measures of mental health (distress symptoms and emotion regulation) will include three 
well-validated scales for diagnostic screening: the 9-item PHQ-9 to screen for depression[6, 
7], the 7-item ( =.92) GAD-7 for anxiety[8], and the Posttraumatic Stress Disorder Checklist 
for DSM-5 (PCL-5),[9] which assesses symptoms of post-traumatic stress on a Likert-type scale 
with 20 items ( =.94). The 4th measure, the Difficulty in Emotion Regulation Scale short form 
(DERS-SF)[10, 99] assesses difficulties in the modulation of emotional arousal. There are 18 
items on a Likert-type scale (DERS  =.93; DERS short form  ranges from .78 to .91 with 
original DERS subscales) and four subscales that assess the degree of awareness, 
understanding, and acceptance of emotions, and the ability to act in desired ways regardless 
of the emotional state. The 5th & 6th measures, the Freiberg Mindfulness Questionnaire (FMQ) 
with 14 items[14], and the Multidimensional Assessment of Interoceptive Awareness 
(MAIA)[15] with 32 items on a Likert-type scale.   
Physical symptoms will be assessed using the Medical Symptoms Checklist (MSC) and pain 
severity and interference using the Brief Pain Inventory (BPI).  The MSC measures the 
frequency (0-8 scale) and severity (0-10 scale) of 29 common physical symptoms.[19] The BPI 
is a validated, widely used measurement tool for assessing clinical pain. In the U.S. it has 
been validated in non-cancer patients with pain[18] and HIV-infected patients.[100] The 
assessment includes 11 questions which provide information on pain severity and pain 
interference in the past week. Participants are initially asked if they have experienced any 
significant pain in the past week, and if they respond positively they answer subsequent 
questions about duration of pain, pain severity and interference. Pain severity is rated from 0 
(“no pain”) to 10 (“worst pain imaginable”), and participants are asked to rate their current 
pain as well as pain at its worst, at its best, and on average in the past week. Pain 
interference includes information on the impact of pain on general activity, walking, work, 
mood, enjoyment of life, relations with others, and sleep, asking the participant to rate 
interference on a scale from 0 (“does not interfere”) to 10 (“completely interferes”), and is 
reported as the mean of seven questions. Participants who responded that they had no pain in 
the past week will be coded “0” for pain severity and interference. The BPI will be 
supplemented with a single question on duration of currently reported pain in order to 
establish whether the pain is acute or chronic. 
Secondary Objective 2 Hypothesis:  MABT + MAT will result in significantly reduced opioid 
craving, and significantly longer retention (days receiving medications), compared to TAU 
only from baseline to 6 months (R33) and baseline to 12 months (R01).   
Opioid craving will be assessed using a single item numeric scale.[5] Participants are asked: 
“On a scale of 0–10, please indicate how much craving you have experienced during the past 
week,” with responses anchored at “0=no craving at all” and “10-strongest craving ever”. 
Retention will be defined as days retained in the program, or time to program discharge. 
Program discharges are documented in the electronic medical record (EMR) and date of 
discharge will be extracted from the record. 
 

 
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Secondary Objective 3 Hypothesis: Among participants in both groups who are using 
substances at 6 months, those in MABT group who receive additional MABT sessions (between 
6-9 months) will show improved substance use at 12 months compared to those in TAU. 
Exploration of the effectiveness of additional MABT dose offered at 6 months to those with 
continued substance use compared to those with continued substance use at 6 months in the 
TAU will be assessed using the Time-Line Follow-Back Interview (TLFB)[3, 4] self-reported as 
described in in the primary objective. 
9.2 
Sample Size and Randomization 
Sample Size Calculation/Power Analysis:  
Primary Objective The power for the primary aim of this study was determined for change in 
the days percent abstinent from opioids on the Timeline Followback Interview (TLFB) 
between the study’s two arms (MABT +TAU, and TAU only) from baseline to 6 months (R33 
aim) and baseline to 12 months (R01 aim).  The power analysis was based on the prior MABT 
SUD R01 study (N=187), in which the proportion of abstinent days for MABT + TAU was 88.6 
compared to 80.0 for TAU at 12 month follow-up.[90] Unlike the count data used to assess the 
number of days abstinent, proportional data is based on exact binomial confidence intervals 
and thus provides reliable and appropriate data to use for sample size calculation. The 
magnitude of effect in this prior R01 is expected to be similar for baseline to 6 month (R33) 
and baseline to 12-month effect for MABT + TAU vs. TAU (R01) in the current study. 
A sample of 330, with an expected loss to follow-up of 20%, allows for .80 power to detect a 
minimum difference in proportion in days abstinent between MABT and TAU of .14, alpha 
=.05, two-tailed. Loss to follow-up is not expected to vary significantly due to treatment 
assignment. Since the actual analyses allow GEE models to analyze five time points (0, 3, 6, 
9, 12 months) simultaneously for the R01 study, power will very likely be higher than these 
conservative estimates.  
Secondary Outcomes For comparison of treatment arms on measures of secondary outcomes, 
we will have 80% power to detect a minimum difference of 0.4 SD. For comparison of 
medication-assisted treatment retention rates, we hypothesize that retention rates at 12 
months will be 60% in the TAU arm and 77% in the MABT arm. The comparison of proportions 
will have power of 80% to detect this difference. Exploratory Aim: at 6 months after 20% 
attrition, we expect the total sample to be N = 264 (132 per group) and assume the ability to 
detect, at minimum, a 15% difference between MABT and TAU groups in proportion of 
abstinent days. Under these assumptions, the power at 12 months to detect a group 
difference comparing those using substances at 6 months (nonresponders) in control to those 
using substances (nonresponders) at 6 months in MABT groups (who have been offered 
additional sessions) is .65 for a 40% non-responder rate (n = 53 per group).  While 
underpowered, this exploratory aim would provide a reasonable sample size to estimate 
power for future related research questions and allows us to look at the question of MABT 
dose and re-engagement for those needing additional treatment support within the primary 
analysis. 

 
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Missing Data: We will evaluate differences in baseline characteristics between participants 
lost to follow-up versus those who are not. Missing data patterns will also be evaluated 
including the frequency and percentage of those missing for each variable and the distribution 
of the number of variables missing. In addition, data collected to the point of lost to follow-
up will be compared to the data of those who complete the study to examine possible missing 
data mechanisms, e.g., missing completely at random (MCAR), missing at random (MAR), or 
not missing at random (NMAR). Sensitivity analyses will be performed to assess the possible 
impact of the missing data on the study results. We will consider various methods for missing 
TLFB including multiple imputation and pattern mixture models.[105] Similar methods will be 
used for other drug use and opioid craving. We anticipate there should be no missing data for 
retention since patients who are lost to follow-up are discharged from the program, therefore 
“missingness” is part of the variable definition. 
Randomization: Randomization will be provided by the project statistician. Stratified 
randomization, by study site, baseline self-reported chronic pain, and gender, will be used to 
distribute participants evenly between the two treatment conditions at each facility and 
within each gender. Randomization will use a modified minimization method algorithm[96] 
based on an overall imbalance score which measures how far out of balance (within strata) 
the study is for a given set of random assignments to ensure approximately equal accrual into 
the two experimental arms and to facilitate concealment of treatment assignments.   
Treatment Assignment Procedures 
Research coordinators will use the randomization program developed by the project 
statistician to determine the treatment assignment group following baseline data collection.  
Participants will be informed of their assignment within one week of the initial appointment 
by the Research Coordinator. Prior MABT studies showed no loss due to randomization to 
treatment group, thus we do not expect randomization to precipitate significant attrition. 
The Research Coordinator at each facility will not be blind to condition and will inform 
participants of their treatment condition and MABT therapist. 
9.3  Definition of Populations 
Intent-to-treat and dose analyses will be used.  Intent to treat analyses includes all 
participants enrolled in the study.  The dose analyses will examine TAU vs. MABT participants 
who completed > 75% of the initial intervention. Exploratory dose analyses will assess the 
impact of additional MABT sessions in the subpopulation of MABT-assigned participants who 
report using substances at the 6 month assessment. 
9.4 
Interim Analyses and Stopping Rules 
No interim efficacy or futility analyses are planned because of the minimal risk level of the 
study and because patient outcomes are very unlikely to be worse in the intervention group in 
the study. 
This study will be stopped prior to its completion only after discussion with and input from 
NCCIH if: (1) the intervention is associated with severe adverse effects that call into question 
the safety of the intervention; (2) difficulty in study recruitment or retention will significantly 

 
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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.   
Pertaining to the likelihood of adverse events, prior studies employing MABT to individuals 
with mental health concerns including two NIH-funded studies for individuals with substance 
use disorder, many of whom had moderate-severe depression and/or anxiety symptoms, and 
three additional studies for women with sexual trauma, have not identified significant risks 
associated with this intervention. However, should adverse events occur that are determined 
to be related to study participation, the MPIs and independent monitor (IM) will consult with 
both the UW IRB and the NICCH Program Officer about the likelihood of continued risk to 
study participants and will make a decision about whether it is necessary to stop the trial.   
Should accrual monitoring demonstrate the need, the MPIs will consult with the data analyst 
and the IM to assess the impact of significant data loss due to problems in recruitment, 
retention, or data collection.  Factors external to the study when interpreting the data, such 
as scientific developments or the new availability of proven clinical services that could have 
an impact on the safety of the participants, the performance of the study or the ethics of the 
study, will be reviewed by the MPIs annually. 
9.5 
Outcomes  
9.5.1 Primary Outcome   
The primary outcome is patient-reported days of abstinence from illicit opioid use measured 
at the 6 month endpoint for the R33 and 12month endpoint for the R01. Self-reported 
substance use is the recommended approach for intervention studies.[97] Days of illicit opioid 
use is defined as the number of days in which opioids other than MAT (buprenorphine or 
methadone) are used.  Time-Line Follow-Back Interview (TLFB)[3, 4] will be used to assess 
opioid use, other illicit drugs, marijuana, and alcohol use. Participants will be asked first to 
identify what substances were used in the previous 90 days at each time assessment point 
(scheduled every 90 days). The participant will then be asked to use a calendar to 
retrospectively estimate their substance use, for each of the identified substances. Days of 
other illicit substance use is defined as the number of days (e.g. cocaine, methamphetamine, 
hallucinogens, or non-prescribed benzodiazepine) are reported using the TLFB.  
9.5.2 Secondary Outcomes   
Measures of mental health (distress symptoms and emotional well-being) will include three 
well-validated scales for diagnostic screening: the 9-item PHQ-9 to screen for depression[6, 
7], the 7-item ( =.92) GAD-7 for anxiety[8], and the Posttraumatic Stress Disorder Checklist 
for DSM-5 (PCL-5),[9] which assesses symptoms of post-traumatic stress on a Likert-type scale 
with 20 items ( =.94). The 4th measure, the Difficulty in Emotion Regulation Scale short form 
(DERS-SF)[10, 99] assesses difficulties in the modulation of emotional arousal. There are 18 
items on a Likert-type scale (DERS  =.93; DERS short form  ranges from .78 to .91 with 
original DERS subscales) and four subscales that assess the degree of awareness, 
understanding, and acceptance of emotions, and the ability to act in desired ways regardless 

 
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of the emotional state. The 5th and 6th measures, the Freiberg Mindfulness Questionnaire 
(FMQ) with 14 items[14], and the Multidimensional Assessment of Interoceptive Awareness 
(MAIA)[15] with 32 items on a Likert-type scale are used to assess skills learned in the 
intervention. 
Opioid craving will be assessed using a single item numeric scale.[5] Participants are asked: 
“On a scale of 0–10, please indicate how much craving you have experienced during the past 
week,” with responses anchored at “0=no craving at all” and “10-strongest craving ever”. 
Retention will be defined as days retained in the program, or time to program discharge. 
Program discharges are documented in the electronic medical record (EMR) and date of 
discharge will be extracted from the record.   
Physical symptoms will be assessed using the Medical Symptoms Checklist (MSC) and pain 
severity and interference using the Brief Pain Inventory (BPI).  The MSC measures the 
frequency (0-8 scale) and severity (0-10 scale) of 29 common physical symptoms.[19] The BPI 
is a validated, widely used measurement tool for assessing clinical pain. In the U.S. it has 
been validated in non-cancer patients with pain[18] and HIV-infected patients.[100] The 
assessment includes 11 questions which provide information on pain severity and pain 
interference in the past week. Participants are initially asked if they have experienced any 
significant pain in the past week, and if they respond positively they answer subsequent 
questions about duration of pain, pain severity and interference. Pain severity is rated from 0 
(“no pain”) to 10 (“worst pain imaginable”), and participants are asked to rate their current 
pain as well as pain at its worst, at its best, and on average in the past week. Pain 
interference includes information on the impact of pain on general activity, walking, work, 
mood, enjoyment of life, relations with others, and sleep, asking the participant to rate 
interference on a scale from 0 (“does not interfere”) to 10 (“completely interferes”), and is 
reported as the mean of seven questions. Participants who responded that they had no pain in 
the past week will be coded “0” for pain severity and interference. The BPI will be 
supplemented with a single question on duration of currently reported pain in order to 
establish whether the pain is acute or chronic. 
Table 1: Outcomes Measurement Schedule  
Concept 
Measure 
Assessment Time-Point (from baseline) 
 
 
Baseline  
12 weeks  24 weeks 
39 weeks 
52 weeks 
Baseline and Descriptive Information 
 
 
 
 
 
Demographic/Health 
History  
Health History 
Form[1],(EHR) 
X 
 
 
 
Trauma history  
TLEQ[2] 
X 
 
 
 
 
Economic Indicators 
Employment, Health 
Utilization, Legal 
Status 
X 
X 
X 
X 
X 
Substance Use  
 
 
 
 
 
 
Substance use   
TLFB Interview[3, 4] 
Urine Toxicology 
Opioid Craving [5] 
Treatment Retention 
(EHR)  
X 
X 
X  
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
Mental Health Distress, Emotional Well-being, 
Physical Health Distress and Pain 
 
 
 
 
 

 
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Distress  
(Depression, Anxiety 
PTSD Symptoms) 
PHQ-9[6, 7] 
GAD-7[8] 
PCL-5[9] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Emotion Regulation 
Difficulties   
 
DERS-SF[10] 
 
X 
 
X 
 
 X 
 
 X 
  
 
 X 
 
Mindfulness and 
Interoceptive 
Awareness Skills  
FMQ [14] 
MAIA [15] 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
Co-morbid Pain and 
Interference 
BPI[18] 
X 
X 
X 
X 
X 
Physical Symptoms 
MSC [19] 
X 
X 
X 
X 
X 
Intervention Satisfaction 
 
 
 
 
 
Treatment satisfaction 
and perceived skills* 
MABT Follow-up 
Questionnaire 
 
X 
 
X 
 
* MABT group only; NA = not applicable; EHR = Electronic Health Records. 
9.6 
Data Analyses  
Primary Analysis  To test the primary hypotheses, generalized linear regression models for 
dependent data will be used to compare percent days abstinent from opioid use in the two 
study groups between baseline to 6 months for the R33 study aims, and baseline to 12 months 
for the R01 study aims.   Sensitivity analyses will also explore modeling opioid use as percent 
days abstinent during the assessment periods using Generalized Estimating Equations (GEE) 
[106] with a logit link and an exchangeable correlation structure. We will fit difference within 
group correlations structures (unstructured, independent, exchangeable, autoregressive) 
seeking the correlation structure that combines the fewest parameters with the best measure 
of fit using Akaike information criterion (AIC) and Bayesian information criterion (BIC). The 
logarithm of the total number of days in the assessment period will be included as an offset 
variable to account for the time at risk of relapse. The same analysis will be done to examine 
percent days abstinent on other illicit drugs and alcohol.  
Secondary Analyses  Analyses of secondary outcomes (mental and physical health outcomes 
and opioid craving) will utilize GEE as described above. Longitudinal analyses will examine 
treatment by time interactions on each of the outcomes. Analyses of retention in medication-
assisted treatment will be done using a test of proportions retained in MAT as well as the log-
rank test to compare survival curves. A sensitivity analysis will use Cox regression to adjust 
for pre-treatment covariates. Last, we plan to include exploratory analyses to also examine 
treatment by gender interactions.  
 
Exploratory Analysis  Linear regression model using GEE will be used to explore the effect of 
additional MABT dose on days abstinent from opioid use and related health outcomes at 12 
months among the MABT 6 month non-responders compared to control non-responders. 
Characteristics of responders will be compared to those of non-responders using t-tests, chi-
square, or Fisher's exact tests. 
In addition, we will explore the relationship with dose, within the MABT group. Dose response 
functions will be estimated thorough a regression approach treating the number of sessions as 
the continuous treatment variable. Such models are appropriate when the treatment intensity 
is endogenous (that is, selection into treatment depends on both observable and unobservable 
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10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1 Data Collection Forms  
Data collection will follow study procedures as specified in standard operating procedures 
developed from the research protocol.  The MPIs will work with the data manager and project 
manager to design forms and a database that maximizes accurate data entry by setting 
appropriate ranges and expected data types (e.g., text, date, etc.).  The project manager 
will ensure the proper procedural trainings occur for the research coordinators and 
interventionists on the data collection procedures and forms, including adherence to 
procedures to protect participant confidentiality (see Section 11.3). 
10.2 Data Management  
Clinical Sites 
The research coordinators (RC) will collect data from participants and the interventionists at 
the clinical sites.  Using a laptop computer with password and network protections, RCs will 
enter demographic information, screening results, tracking data, primary outcome (TLFB) 
data, urine toxicology results, and EHR-derived retention data directly into the secure study 
databases.  During assessment visits, RCs will open the survey instruments via REDcap on the 
laptop (in a guest-only UW account) and allow participants to complete the measures 
independently (unless he/she requires assistance due to low/no literacy, for which the RC will 
read and record survey information).  Paper consent files will be stored in a locked filing 
cabinet separately from paper files (e.g., TLFB calendar worksheet, handwritten process 
evaluations) associated with the participant’s study ID number. 
Interventionists will provide the RC with process evaluations and session audio files, which the 
RC will upload to the secure server.  Interventionists will also provide the RC with AE/SAE 
related forms if reported during the session. 
Data Management Center 
The data manager, project manager, and MPIs will be responsible for creating and 
maintaining the study databases.  Survey measure data will be collected and stored in 
REDcap.  Tracking data and non-survey outcomes data entered by the RCs at the clinical sites 
will be stored in REDcap, Access, or Excel and monitored as described in section 10.3.5 
below. 
 
Data Collection Forms 
Data collections forms are mostly electronic using primarily radio buttons to complete Likert-
type scales.  A paper calendar is used to elicit illicit drug use recall in the TLFB procedures 
and to calculate totals, and the results entered into the REDCap database along with 
urinalysis results.  Paper forms will be used to record process evaluations and events (e.g., 
AE/SAE, UP, PD), then submitted to the RC to be scanned and uploaded to the secure shared 
server folder or for electronic input into the study database. 

 
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10.3 Quality Assurance  
10.3.1 Training 
The research coordinators will be directly overseen by the project manager and the MPIs.  
Coordinators will undergo training including reading and review of the Standard Operating 
Procedures of the study and skills review of accessing and entering data.  Meetings every two 
weeks between the project manager and RCs, and monthly including Dr. Price, will provide 
RCs opportunity to discuss issues that arise; however, they will be encouraged to reach out at 
any time with questions or concerns regardless of scheduled meetings. 
The MABT interventionists will be licensed to practice in Washington State, as massage 
therapists (LMT) or mental health counselors (licensed clinical social workers or mental health 
counselors). They will have clinical experience working with individuals in SUD treatment and 
an educational background in mental health (graduate degree or certificate training), and a 
minimum of 5 years in clinical practice. The interventionists will be trained to the MABT 
protocol by Dr. Price.  
To track treatment fidelity, the research interventionists will complete a process evaluation 
form that includes a fidelity checklist (an integral part of the MABT training manual and 
protocol) at the completion of each intervention session. In addition, all intervention sessions 
will be audio-recorded to monitor compliance to the research protocols and to facilitate 
ongoing clinical supervision. Ms. Wiechman, a trained MABT therapist and instructor who has 
worked on multiple prior MABT research studies with Dr. Price, will supervise the MABT 
interventionists. Supervision will include ongoing review of audiotaped sessions and process 
evaluation forms and regular feedback to interventionists based on this review. 
10.3.2 Quality Control Committee  
There is no quality control committee.  Data quality and protocol adherence will be 
monitored by the study team. 
10.3.3 Metrics 
Data collected via REDCap surveys/databases allow set ranges and the inability to select 
multiple responses thus ensuring that a single and valid response for each item is collected. 
Distribution properties, scale means and variances for all outcome measures will be 
scrutinized. We will conduct measurement studies with data from this study, performing 
validity (correlations, CFA) and traditional reliability analyses (Cronbach’s ) for all 
measures. 
10.3.4 Protocol Deviations 
Protocol deviations will be captured by review of data and related procedures on a regular 
basis by the Project Manager (supervising RC) and PI providing supervision of interventionists 
(Dr. Price). These deviations will be recorded and saved on the protected study database, and 
reviewed with the larger team at the regularly scheduled team meetings, or sooner if 
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10.3.5 Monitoring 
Results of data checks (including those in table 4) and for outcomes as described in 10.3.3 
will be shared with the MPIs at quarterly team meetings, or sooner if repeated errors are 
found. Compliance will be addressed by quarterly audits/monitoring of study-related 
materials (e.g., consent forms, source documents, adverse event logs, etc.). 
 
Table 4.  Data Monitoring 
Data Type 
Frequency of Review 
Reviewer 
Subject accrual (including 
compliance with protocol 
enrollment criteria) and 
meeting milestones 
Every 2 weeks 
Monthly 
Quarterly 
Project Manager 
MPIs 
Independent Monitor (by 
report) 
Status of all enrolled 
subjects, as of date of 
reporting 
Monthly 
Quarterly 
Project Manager 
MPIs 
Independent Monitor (by 
report) 
Adherence data regarding 
study visits and intervention 
Monthly 
Quarterly 
Project Manager 
MPIs,  
Independent Monitor (by 
report) 
AEs and rates  
Weekly 
Quarterly 
Project Manager, MPIs 
Independent Monitor (by 
report) 
Unanticipated, serious, 
possibly related SAEs 
Per occurrence 
MPIs, Independent Monitor, 
NCCIH 
Reportable New Information 
(e.g., unanticipated 
problem, serious non-
compliance) 
Per occurrence 
MPIs, UW IRB, Independent 
Monitor 
 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 Institutional Review Board (IRB) Review  
We will receive approval from the University of Washington Institutional Review Board before 
commencing the study with human subjects, and will adhere to its policies regarding 
subsequent modifications to the approved application.   
11.2 Informed Consent Forms 
Verbal informed consent will be obtained prior to initiating screening procedures. A signed 
consent form will be obtained from each participant. The consent form 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 or legal guardian and this fact will be 
documented in the participant’s record. Individuals who cannot provide informed consent will 
be excluded, such as in the scenario of acute intoxication, overt psychosis or cognitive 

 
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impairment, as well as participants who do not speak or read English. An adapted 7-item Mini-
Mental Status Exam, with a cut-off score indicating ineligibility, will be applied if there is 
questionable difficulty comprehending the informed consent and to assess cognitive 
impairment.  
11.3 Participant Confidentiality  
The structures to assure confidentiality include the following: each enrolled participant will 
receive a unique identification number; research data collection and data entry forms will be 
identified only with this number. Only the master enrollment list, written informed consent 
forms, and participant locator information will have identifying information on them. These 
documents will be kept on a secure network or in a locked file cabinet in the PI and project 
manager’s offices. Computer systems will be password protected, and accessible only to 
research staff needing the information for follow-up and monitoring purposes. Files stored on 
UW servers will be protected by electronic ‘firewalls’ that restrict access to designated users. 
The data manager will receive only coded information entered into the database under study 
ID numbers. Any data, forms, reports, recordings, and other records that leave the site will 
be identified only by a participant identification number (Participant ID, PID) to maintain 
confidentiality. No study information will be released without written permission of the 
participant, except as necessary for monitoring by IRB, NCCIH, and the OHRP.  We also will 
preserve confidentiality during adverse event reporting, by not including any identifying 
information unless invoking the UW Human Subjects Assistance Program at the request of an 
eligible study participant.  
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. 
12. COMMITTEES 
Not applicable. 
13. PUBLICATION OF RESEARCH FINDINGS  
Research findings will be disseminated through presentations, abstract submissions, and 
manuscripts with appropriate acknowledgement and disclaimer of NCCIH.  Dissemination 
efforts also include sharing of best practices across SAMHSA networks, allowing a platform for 
widespread implementation of successful strategies, which can facilitate the adoption of 
MABT to improve MAT and related health outcomes, a key goal of the WA-STR project.  For 
example, integration of this trial within programs funded through the Washington State STR 
Hub & Spoke Project allows for future expansion of the intervention should trial data show 
improved treatment outcomes. Each of the six Hub & Spoke networks funded through STR 
plan to incorporate elements of the Nurse Care Manager model in a variety of primary care, 
behavioral health and substance use disorder treatment programs with connections to key 

 
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community sites, including needle and syringe exchange programs, hospitals, correctional 
facilities, and drug courts. In addition, real world evidence of MABT effectiveness within WA-
STR would be an important step towards establishing it as qualifying for inclusion within 
SAMHSA’s National Registry of Evidence-Based Programs and Practices. 
14. REFERENCES  
1. 
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Kubany, E.S., et al., Development and preliminary validation of a brief broad-
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3. 
Sobell, L. and M. Sobell, Alcohol Timeline Followback User's Manual. 1995, Toronto: 
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5. 
Rosenberg, H., Clinical and laboratory assessment of the subjective experience of 
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Kroenke, K., R.L. Spitzer, and J.B. Williams, The PHQ-9: validity of a brief depression 
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Kroenke, K., et al., The Patient Health Questionnaire Somatic, Anxiety, and 
Depressive Symptom Scales: a systematic review. Gen Hosp Psychiatry, 2010. 32(4): p. 
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8. 
Spitzer, R.L., et al., A brief measure for assessing generalized anxiety disorder: the 
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9. 
Dickstein, B.D., et al., Diagnostic Utility of the Posttraumatic Stress Disorder (PTSD) 
Checklist for Identifying Full and Partial PTSD in Active-Duty Military. Assessment, 
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Kaufman, E., et al., The difficulties in emotion regulation scale short form (DERS-SF): 
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Diener, E., et al., New well-being measures: short scales to assess flourishing and 
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Keyes, C.L., Promoting and protecting mental health as flourishing: a complementary 
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Smith, B.W., et al., The brief resilience scale: assessing the ability to bounce back. 
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Walach, H., et al., Measuring mindfulness - the Freiburg Mindfulness Inventory (FMI). 
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Bagby, R.M., G.J. Taylor, and J.D. Parker, The Twenty-item Toronto Alexithymia 
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Parker, J.D., G.J. Taylor, and R.M. Bagby, The 20-Item Toronto Alexithymia Scale. III. 
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18. 
Keller, S., et al., Validity of the brief pain inventory for use in documenting the 
outcomes of patients with noncancer pain. Clin J Pain, 2004. 20(5): p. 309-18. 
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Leserman, J., et al., Selected symptoms associated with sexual and physical abuse 
history among female patients with gastrointestinal disorders: the impact on 
subsequent health care visits. Psychol Med, 1998. 28(2): p. 417-25. 
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opioid crisis. 2016. 
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