mHealth to Help Pregnant and Postpartum Women in Recovery for Opioid Use Disorder
Phase: EARLY_PHASE1
Conditions: Opioid Use Disorders
Sponsor: Washington University School of Medicine

 
 
 
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mHealth to Help Pregnant and Postpartum Women in Recovery 
for Opioid Use Disorder or Stimulant Use Disorder 
Principal Investigators: Patricia Cavazos-Rehg, Ph.D. 
Hannah S. Szlyk, Ph.D., LCSW 
 
 
 
 
 
 
 
 
 
 
 
 
Version 18 – 10/27/2023 

 
 
 
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Table of Contents 
 
Contents 
Introduction ................................................................................................................................................................... 4 
A1 
Study Abstract ............................................................................................................................................ 4 
A2 
Primary Hypothesis.................................................................................................................................... 4 
A3 
Purpose of the Study Protocol .................................................................................................................... 4 
B 
Background ........................................................................................................................................................... 4 
B1 
Prior Literature and Studies ....................................................................................................................... 5 
B2 
Rationale for this Study ............................................................................................................................. 6 
C 
Study Objectives.................................................................................................................................................... 6 
C1 
Primary Aim............................................................................................................................................... 6 
D 
Study Design .......................................................................................................................................................... 6 
D1 
Overview or Design Summary ................................................................................................................... 7 
D2 
Subject Selection and Withdrawal ............................................................................................................. 7 
2.a 
PPWP Inclusion Criteria ........................................................................................................................... 7 
2.a 
Exclusion Criteria ...................................................................................................................................... 7 
2.b 
Ethical Considerations............................................................................................................................... 7 
2.c 
Subject Recruitment Plans and Consent Process ....................................................................................... 7 
2.d 
Randomization Method and Blinding ......................................................................................................... 8 
2.e 
Risks and Benefits ...................................................................................................................................... 8 
2.f 
Early Withdrawal of Subjects .................................................................................................................... 8 
2.g 
When and How to Withdraw Subjects ........................................................................................................ 9 
2.h 
Data Collection and Follow-up for Withdrawn Subjects ........................................................................... 9 
D3 
uMAT-R Intervention ................................................................................................................................ 9 
3.a 
Description ................................................................................................................................................ 9 
3.b 
Treatment Regimen .................................................................................................................................. 11 
3.c 
Administration of uMAT-R ....................................................................................................................... 11 
3.d 
Technical Development of uMAT-R .......................................................................................................... 11 
3.e 
Prior and Concomitant Therapy .............................................................................................................. 11 
E 
Study Procedures ................................................................................................................................................ 11 
E1 
Screening for Eligibility ........................................................................................................................... 11 
E2 
Schedule of Measurements ...................................................................................................................... 11 
E3 
Safety and Adverse Events ....................................................................................................................... 15 
3.a 
Safety and Compliance Monitoring ......................................................................................................... 15 
3.b 
Safety Monitoring .................................................................................................................................... 15 
3.c 
Definitions of Adverse Events .................................................................................................................. 15 
3.d 
Data Collection Procedures for Adverse Events ...................................................................................... 16 
3.e 
Reporting Procedures .............................................................................................................................. 16 
3.f 
Adverse Event Reporting Period .............................................................................................................. 16 
E4 
Study Outcome Measurements and Ascertainment .................................................................................. 16 
F 
Statistical Plan ..................................................................................................................................................... 17 
F1 
Sample Size Determination and Power .................................................................................................... 17 
F2 
Interim Monitoring and Early Stopping ................................................................................................... 17 

 
 
 
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F3 
Analysis Plan ........................................................................................................................................... 17 
G 
Data Handling and Record Keeping .................................................................................................................. 18 
G1 
Confidentiality and Security .................................................................................................................... 18 
G2 
Training ................................................................................................................................................... 18 
G3 
Source Documents ................................................................................................................................... 18 
G4 
Records Retention .................................................................................................................................... 18 
H 
Study Administration .......................................................................................................................................... 18 
H1 
Organization and Participating Centers.................................................................................................... 18 
H2 
Funding Source and Conflicts of Interest ................................................................................................. 18 
H3 
Subject Stipends or Payments .................................................................................................................. 19 
H4 
Study Timetable ....................................................................................................................................... 19 
I 
Publication Plan .................................................................................................................................................. 20 
J 
Attachments ......................................................................................................................................................... 20 
J1 
Tables ....................................................................................................................................................... 20 
K 
References ............................................................................................................................................................ 20 
 

 
 
 
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Introduction 
A1 Study Abstract 
The opioid and stimulant epidemic has resulted in widespread detrimental consequences 
among vulnerable populations, especially among pregnant and postpartum women and people 
(PPWP) with opioid use disorder (OUD) and stimulant use disorders. Although perinatal use of 
medication for OUD (MOUD) (previously called medication assisted treatment, MAT) within a 
comprehensive treatment plan is the current standard of care for those with OUD or SUD, 
PPWP struggling with addiction may underestimate or misjudge its benefits. In this project, we 
will utilize a theory-based digital therapeutic tool, uMAT-R mobile application (“app”), to educate 
and motivate PPW) with OUD or SUD. We will assess uMAT-R’s usability among PPWP 
recruited from the addiction treatment facilities. We will also educate PPWP about local 
recovery community centers (RCCs) and link participants to these centers, in attempt to 
cultivate recovery capital. Recovery capital includes personal and environmental resources, 
such physical and mental health, social networks and support, and motivation for recovery. 
RCCs are primed to help individuals acquire recovery capital and often feature voluntary, peer-
led recovery focused initiatives. 
With Aim #1, we  will garner qualitative input from PPWP with OUD or SUD (target users) on the 
intervention components of uMAT-R for feedback on adaptation and implementation. 
Participants’ input on methods to  increase participation and retention for follow-up assessments 
will also be obtained. We will conduct interviews with PPW with OUD or SUD (total n= 64) 
recruited from addiction treatment facility, with 24 local providers who serve PPWP with OUD or 
SUD and/or work at local recovery community centers (RCCs). We will also collect survey and 
follow up interviews among PPWP participants at 1-month to further assess the usability and 
acceptability of this tool among PPWP to inform future evaluations of preliminary efficacy 
among this group.  This novel technology-based intervention could be an invaluable tool to 
assist providers in the treatment of OUD or SUD among PPW. 
 
A2 Primary Hypothesis 
AIM #1: We will garner qualitative input from PPWP with OUD or SUD (target users) and local 
providers on the intervention components of uMAT-R for feedback on the adaptation and 
implementation. Participants’ input on methods to increase participation and retention for follow- 
up assessments will also be obtained. We will conduct interviews with PPWP with OUD or SUD 
(total n= 64) recruited from addiction treatment facility, and with 24 local providers who serve 
PPWP with OUD or SUD. We will also follow up with participants to gather additional feedback 
on their experiences with uMAT-R and recovery after at 1 month (survey, interview). 
 
Π  
Hypothesis: We hypothesize that our participants will report good efficiency, technical 
effectiveness, and satisfaction with uMAT-R, and will provide useful feedback for app 
improvements. 
 
A3 Purpose of the Study Protocol 
The purpose of this protocol is to outline the methods utilized in this study. As we are 
researching a particularly vulnerable population (PPWP) with opioid use disorder or stimulant 
use disorder, this protocol also details the protections we have taken to ensure the safety of 
our participants. 
 
B Background 

 
 
 
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B1 Prior Literature and Studies 
Prevalence and Treatment of Opioid and Stimulant Misuse. Recent trends indicate 
increased use of opioids and stimulants among adults, contributing to several adverse public 
health outcomes. Opioids are a main contributor of overdose deaths across the US. The 
prevalence of OUD and stimulant misuse during pregnancy is likewise increasing.1 
Stimulants such as methamphetamine pass through the placenta and blood brain barrier and 
can have significant effects on the fetus and the newborn. Opioid agonists will also cross the 
placental barrier in concentrations consistent with maternal dose,3-5 and may adversely affect 
the fetus. Additionally, the postpartum period represents a time of increased vulnerabilities, and 
women and people with opioid use disorder relapse far more often in the postpartum period 
compared to with during pregnancy.7 
The Benefits of MOUD. Perinatal use of MOUD within comprehensive treatment is the current 
standard of care alternatives (i.e., withdrawal or detoxification) run the risk of relapse and 
treatment dropout.1 Unfortunately, PPWP struggling with OUD may underestimate or misjudge 
the benefits of MOUD and/or may lack support outside of the clinic to sustain motivation for 
recovery; these barriers could compromise treatment compliance.8-10 For instance, common 
misperceptions about MOUD are that MOUD is substituting one addiction for another; MOUD is 
ineffective because it does not immediately cure dependence;8,11,12 and for PPWP with OUD, 
it is not well known how MOUD will affect both them and their unborn child.1,13,14 To 
supplement providers’ efforts at educating patients, we will develop a digital therapeutics tool, 
uMAT-R, to target one’s (lack of) knowledge and/or negative beliefs that may deter MOUD use. 
To supplement traditional in-person psychiatric care, we will also include features within uMAT-
R to encourage adherence to MAT, support women and people in their everyday lives, and help 
keep them motivated on their path to recovery. 
The Role of RCCs. Guided by stress and coping theory, it can be assumed that greater access 
to recovery capital may enable persons with OUD or SUD to be better prepared to manage 
life’s stressors and achieve recovery. RCCs are primed to help individuals acquire recovery 
capital. RCCs are not aligned with a specific recovery framework, allowing for RCCs to be a 
part of various pathways to recovery. In the greater St. Louis area (including Missouri and 
nearby Illinois), more RCCs are emerging. Overall, these RCCs provide recovery support and 
resources in person and virtually, which allows for flexibility during the COVID-19 pandemic and 
for individuals who may have barriers to transportation. While there is a regional need for OUD 
and SUD care for PPWP, there is little knowledge on how this population transitions to the next 
stage in their recovery post-discharge from a structured, clinical program. In the current 
proposal, in addition to a focus on continued MOUD uptake/ adherence via improved MOUD 
attitudes and beliefs, app-based content and within app e-coaching will promote engagement in 
local RCC’s by increasing participants' knowledge about recovery and improving their recovery 
capital and motivation to stay sober. 
 
Preliminary Study: Testing a prototype of uMAT-R. The use of a prototype of uMAT-R that 
we developed in partnership with iTether (IRB ID 201706044) was piloted with 29 participants 
with OUD. For this pilot, we recruited individuals who were socially networking about opioid 
abuse on social media. The features of uMAT-R were guided by SAMHSA online resources 
about MOUD.15 Our uMAT-R prototype described the cost of MOUD, presented the latest 
research about MOUD efficacy, and described potential side effects of MAT. Video testimonials 
from individuals who have had success with MOUD were also provided. Following their use of 
this digital therapeutic tool, feedback from participants was overwhelmingly positive. In addition, 

 
 
 
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the app increased positive attitudes about MOUD (pre-app mean score 3.31, sd 0.46; post-app 
mean score 3.46, sd 0.52; t(25)=2.12, p=0.044) and interest in starting treatment (pre-app 32%, 
post-app 48%; McNemar’s test p=0.046). This study demonstrates our ability to partner with 
iTether to develop an efficacious digital therapeutic tool that improves MOUD attitudes among 
individuals struggling with OUD. We will adapt the educational content of this prototype to 
address the concerns of PPWP who misuse opioids as well as add daily tips and tailored 
guidance from an online coach. 
 
B2 Rationale for this Study 
Digital therapeutics can help to combat the opioid and stimulant epidemic. Many 
individuals, including those who are struggling with substance use disorder, have interest in 
using apps to support their recovery;16 likewise, our preliminary research has shown that 
individuals with OUD and stimulant use disorder have also demonstrated a willingness to try 
digital therapeutics and that they can efficaciously improve MAT attitudes. Furthermore, digital 
therapeutic tools have the potential to deliver therapeutic content in an accessible and 
engaging modality that exists at one’s disposal, encourages adherence to treatment, and 
delivers personalized support outside of clinical care. However, there are no known published 
studies that evaluate the efficacy of an app focused on supporting PPWP with OUD towards 
MOUD treatment adherence. To address this critical gap, we will develop and pilot test the 
components of uMAT-R, a digital therapy, to provide a sustainable, low-cost intervention to 
educate, motivate, and support OUD and SUD recovery among PPWP with OUD and/or OUD. 
 
C Study Objectives 
C1 Primary Aim 
To assess the feasibility of linking PPWP with the uMAT-R app as a supplement to 
addiction  treatment and explore usability characteristics of and engagement with uMAT-R. 
 
Activities for Aim #1: We will garner qualitative input from PPWP with OUD or SUD (target 
users) on the intervention components of uMAT-R for feedback on the adaptation and 
implementation. Participants’ input on methods to increase participation and retention for follow-
up assessments will also be obtained. We will conduct interviews with PPWP with OUD or SUD 
(total n= 64) recruited from addiction treatment facility and/or through referrals received from 
other participants and members of the community. Twenty-four local providers who treat OUD 
will also be recruited to provide their feedback Guided by the International Organization for 
Standardization,17 we will assess 3 domains of usability characteristics: efficiency, technical 
effectiveness, and satisfaction with uMAT-R, as well as the level of engagement with the app. 
Using a mixed methods approach, we will explore how uMAT- R fared in regard to its ease of 
understanding, helpfulness, intuitive flow, presentation, and pacing. 
 
We will also collect survey and follow up interviews among PPWP participants at 1-month to 
further assess the usability and acceptability of this tool among PPWP to inform future 
evaluations of preliminary efficacy among this group.   
 
C2 Rationale for the Selection of Outcome Measures 
This study will use a combination of quantitative and qualitative measures to examine the 
usability characteristics of and engagement with uMAT-R (Aim #1). 
 
D Study Design 

 
 
 
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D1 Overview or Design Summary 
In this study, we will recruit 64 adult (≥18 years) PPWP for their opioid use disorder at various 
addiction treatment facilities. An additional 24 local providers who treat OUD will be recruited to 
provide their feedback. All participants will receive access to uMAT-R. PPWP participants will 
complete quantitative online survey assessments at baseline and at 1 month follow up. After 
having access to the app for 1 week, all participants will be asked to take part in an interview to 
provide in-depth feedback about their experience with uMAT-R (conducted in-person or via 
Zoom or phone). After 1 month, PPWP participants will also be asked to take part in a follow up 
interview to provide additional information on their lieved experience with SUDs and other 
recovery-related constructs. All interviews will be transcribed verbatim for qualitative analyses. 
 
D2 Subject Selection and Withdrawal 
 
2.a 
PPWP Inclusion Criteria 
1) 
Receiving treatment at a consenting treatment facility and/or referred from other 
participants or community partners 
2) 
Misused opioids or stimulants at some point in their life 
3) 
Pregnant (second or third trimester) or postpartum within the past three years 
4) 
Adult (≥18 years of age) 
5) 
U.S. resident 
6) 
Own a smartphone with an iOS or Android operating system 
 
 
Provider Inclusion Criteria 
1) 
Works with pregnant and postpartum people with opioid use disorder and/or at a recovery 
community center (e.g. a staff person, counselor, social worker, psychiatrist, nurse). 
2) 
Adult (≥18 years of age) 
3) U.S. resident 
 4)  Fluent in English 
 5) Own a smartphone with an iOS or Android operating system 
 
2.a 
Exclusion Criteria 
1) 
Currently incarcerated 
 
2.b 
Ethical Considerations 
Participation in this study is voluntary. All participants will be required to provide verbal consent 
prior to participation. A member of the study team will go over the consent document and 
answer any questions. 
 
2.c 
Subject Recruitment Plans and Consent Process 
Eligible participants (N=64) will be recruited from various addiction treatment facilities or 
community referrals. PPWP coming to the facility receive addiction treatment (medication + 
counseling), and are closely supervised (e.g., weekly visits, urine drug screens, counseling 
session attendance) by the medical team. The research team will meet with various groups that 
could be eligible for the study. We are also requesting a waiver of documented consent for 
participants in this study, as this study poses minimal risk, and we have systems in place to 
protect the confidentiality of our participants. The research team will review the informed consent 
document with participants via phone, and participants may provide verbal consent to take part in 
the study. The research team will continue to follow up with participants via phone, email, and 
within the app to complete necessary follow-up activities. Prospective participants who have been 

 
 
 
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referred by another participant or another community partner can reach out to our team via phone 
to complete the screener over the phone and can enrolled if they are eligible. In some cases, the 
study team may ran into the same participants at the treatment facilities. If the participants 
expresses interest in the study again, the participant will be asked to fill out a screener. A 
research team member will then check to see if the participant has accessed the uMAT-R app 
during their previous participation. If the participant has accessed the uMAT-R app in their 
previous study participation, they are not eligible to be reconsented to the study. Participants who 
are enrolled into the study but have yet to complete their baseline survey and log into the app will 
be able to be reconsented to the study as they approach their 1-week study period. 
 
Specifically, for the CARE Clinic at Washington University School of Medicine, the research 
team will view their Monday afternoon clinic schedule in EPIC to see when individuals are 
scheduled that could be eligible for the study. 
 
2.d 
Randomization Method and Blinding 
There will be no randomization or blinding. We will recruit 64 PPW and 24 local OUD 
providers, all of whom will test the uMAT-R app to provide feedback to inform future 
iterations of the digital tool. 
 
2.e 
Risks and Benefits 
 
Potential Risks 
The potential risks to respondents from participating in this study are unlikely and low risk. The 
uMAT-R mobile app, online questionnaires, and interviews will be confidential. 
 
PPWP participating in this study will be patients of various addiction treatment facilities. If there 
is any concern that a participant is at risk for injury or relapse during conversations with the in- 
app coach, then the participant’s treatment team will be notified. 
 
Participation in all aspects of the study will be on a volunteer basis; participants will have the 
right to refuse answering and/or taking part in particular aspects of the study, and they will be 
told of their right to refuse and/or withdraw from this study at any time. Participants will also be 
instructed of the risks and benefits of their participation in the research and of all the procedures 
to be followed in case of adverse events. These details will be explained to participants during 
the informed consent process.  
Potential Benefits 
uMAT-R will educate adults to improve deficits in recovery knowledge and ultimately increase 
the likelihood of adhering to recovery. Furthermore, because adults with substance use disorder 
(specifically OUD or SUD) may lack support outside the clinic office, uMAT-R will be designed to 
support one’s motivation towards recovery. We expect that after engaging with uMAT-R, PPWP 
participants will better understand the facts about recovery benefits and have increased 
acceptance of recovery. We also expect the PPWP participants to have increased favorable 
recovery attitudes, and recovery capital. Additionally, there are important potential benefits to the 
medical community seeking to improve substance use treatment outcomes. Our findings would 
help to demonstrate whether uMAT-R has the potential to be a beneficial tool for adults who 
misuse substances and could help to bridge the gap between what occurs during a clinical visit 
and what one does and needs in everyday life in order to successfully recover. Client will be 
able to continue accessing the app post study timeframe as a service from our team. 
 
2.f 
Early Withdrawal of Subjects 

 
 
 
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Participants will be able to stop participating in the study at any time. If a participant chooses to 
withdraw from the study and intervention, they will no longer have access to uMAT-R and will 
only be compensated for completed assessments. 
 
2.g 
When and How to Withdraw Subjects 
In the case of an adverse event (detailed below), the research team could determine that it is no 
longer safe for a participant to continue in the study. The research team will inform both the 
participants treatment team and the participant that they are being removed from the study. The 
participants treatment team will then assume responsibility for appropriate follow-up and care. 
 
2.h 
Data Collection and Follow-up for Withdrawn Subjects 
In the event that a participant withdraws from the study, there will be no further data collection or 
follow-up. 
 
D3 uMAT-R Intervention 
 
3.a 
Description 
The uMAT-R intervention will consist of several features designed to educate PPWP with OUD 
about MOUD in order to counter their misconceptions and/or improve deficits in MOUD 
knowledge. Lastly, the app will include general tools to promote a healthy pregnancy, 
postpartum recovery, and overall  recovery skills. 
 
Educational content: uMAT-R delivers educational content in plain, understandable language, 
which promote the use of and adherence to MOUD, engagement with RCCs, sustained OUD 
and SUD recovery, general pregnancy and postpartum knowledge, sexual health, and other 
topics regarding healthy lifestyles and emotional wellbeing. Educational materials will be 
derived from sources such as Journey Recovery Project (https://journeyrecoveryproject.com/#/ 
home), the American College of Obstetricians and Gynecologists (ACOG), HealthWise, and 
other government websites. Materials from these sources will be compiled and reorganized into 
topics that are easy-to-navigate. 
 
Brief recovery tips: uMAT-R contains a “library” of brief recovery tips that are informed by 
cognitive behavioral therapy (CBT).18,19 These tips will focus on their cognitive restructuring 
and behavioral changes, including (a) psychoeducation about dependence, craving, and 
relapse; (b) how to identify risk factors and triggers for relapse; (c) techniques for avoiding 
situations with a high risk of relapse and how to intervene in those situations; and (d) developing 
healthy and regular alternative habits. 
 
E-coach: Within uMAT-R’s in-app messaging feature, PPWP participants will be encouraged to 
directly communicate with a coach. Dr. Cavazos, a licensed psychologist and Dr. Szlyk, a 
doctoral-level licensed clinical social worker – both MPIs of this study – will oversee members 
of the research team directly involved with coaching participants. Zhuoran Zhang has a 
master’s in experimental psychology and has accumulated valuable clinical experience over the 
course of the year as part of the e-coaching team. Elecia Worley is a masters-level social 
worker with remote and in-person clinical experience from her previous positions. They will 
assist Drs. Szlyk and Cavazos in managing and overseeing the coaching staff. Coaches will 
employ techniques from the Motivational Interviewing (MI) model. 20 MI is patient-centered and 

 
 
 
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strives to increase insight and awareness about risks related to unhealthy substance use and to 
heighten motivation for one to move to a higher degree of readiness to change.20 The MI model 
has been shown to reduce substance use,21-24 and is especially conducive to digital 
therapeutics because it allows for flexibility in tailoring interactions and encourages an 
empathetic social listening style while soliciting individuals to reflect on their unique reasons for 
behavior change. 
Goals Setting and Reminders: E-coaches can help to goals related to recovery in the 
app for participants based on needs expressed in messaging and in-app assessments. 
PPWP Participants will receive medication and upcoming appointment reminders. 
 
Resources: uMAT-R e-coaches can provide information to participants on important 
resources, including local RCCs, suicide crisis lines and local St. Louis Narcotic Anonymous 
meetings. Other resources include where to seek support with housing and access to food 
and clothing, support with education/employment, and specific services for PPWP and child.  

 
 
 
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3.b 
Treatment Regimen 
Participants will have access to uMAT-R for 1 month in this study. They will be encouraged 
to use all app features during this time. 
 
3.c 
Administration of uMAT-R 
After consenting, participants will be provided with instructions on how to download uMAT-R. 
 
3.d 
Technical Development of uMAT-R 
Reconnect is a mobile health development company that has developed a digital platform 
comprised of proprietary software in communication with an online database that works to 
enable behavioral health providers to deliver digital content and interact with their clients. 
Reconnect has worked with behavioral health providers and organizations  and has partnered 
with our research team to develop uMAT-R. 
 
3.e 
Prior and Concomitant Therapy 
All participants are also patients of addiction treatment facilities and will be receiving their 
standard treatment for both OUD or SUD and perinatal care. 
 
 
E Study Procedures 
E1 Screening for Eligibility 
PPWP coming to a STR Treatment Agency, Federal Qualified Health Center, or another local 
substance use treatment center are provided with opiate and/or stimulant addiction treatment 
(counseling) and are closely supervised by their behavioral health team. The research team will 
meet with various groups that could be eligible for the study. A member of the research team 
will then go over the consent document in person or over the phone  with the participant. If a 
client is not eligible for the intervention due to not having access to a cellphone, they will be 
asked if they want to complete the baseline survey. Prospective participants who have been 
referred by another participant or another community partner can reach out to our team via 
phone to complete the screener over the phone and can enrolled if they are eligible. 
 
Specifically, for CARE Clinic at Washington University School of Medicine, the research team 
will view their Monday afternoon clinic schedule in EPIC to see when individuals are scheduled 
that could be eligible for the study. 
 
E2 Schedule of Measurements 
 
 
Table 1. Study Measures for Aims #1 
Measure 
 
Self-report 
assessments 
collected from 
participants 
Data collected via other 
sources 
Provider demographic 
characteristics survey 
Providers complete brief survey that asks about 
demographic characteristics, current work details, 
and previous work history. 
Collected a 
baseline via 
REDCap 

 
 
 
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USE questionnaire 
Participants will rate ease of use and learning 
(i.e., Efficiency), usefulness (i.e. Technical 
effectiveness), and likability (i.e., Satisfaction) 
on a seven-point Likert scale (1 = strongly 
disagree, 7 = strongly agree), as well as open-
ended items asking participants to list the most 
negative and positive aspects of uMAT-R. 
X- collected after 
1-week of app use 
Primary Outcomes 

 
 
 
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Engagement with 
uMAT-R 
1) Number of times logged into the app, 2) time 
spent in the app once logged in, 3) time difference 
between app logins, and 4) number of interactions 
with the coach 
Participants will provide feedback for the following: 
1) uMAT-R app download 2) viewing of  
instructional video 3) daily app use 4) completion  
of daily assessments 
Automatically collected 
within the app 
Collected from Epharmix 
messaging 
MOUD uptake and 
adherence 
8 questions about lifetime and current use, 
including reasons for not using MOUD; Urine 
screening results, obtained through participant 
medical records and the Modified Morisky Scale; 
self-reported assessment of medication 
compliance through 6 items that measure 
knowledge and motivation 
X 
 
RCC engagement 
On the app, participants will be asked to record 
their weekly engagement with the local RCCs (in-
person or remote). For example: attended a peer 
support group (AA/NA), attended a Narcan 
training, met with a career counseling, attended a 
workshop on parenting/maternal health, attended 
workshop on healthy living, contacted peer 
counselor, or other. 
X 
 
Attitudes 
An 8-item tool to evaluate participants’ attitudes 
towards MAT, modified from the Attitudes of 
Methadone Scale37 
X 
Depression and 
anxiety 
PHQ-9 and GAD-7 used to assess current 
depression and anxiety 
X 
Suicide risk 
Interpersonal Needs Questionnaire to 
assess connection, burdensomeness, and 
thwarted belongness- 3 factors related to 
elevated suicide risk 
X 
Substance use history 
Assessment of current opioid and other illicit drug 
misuse, including assessment of  overdose history 
and cravings 
X 
Opioid use 
Self-reported recreational substance use 
(past 30 days) 
X 
 
Barriers to treatment 
Assesses both potential barriers to obtaining 
treatment prior to the study as well as actual 
barriers to obtaining treatment after the study 
X 
Pregnancy and 
Postpartum 
Revised Prenatal 
Distress 
Questionnaire (PDQ) 
Assesses stress originating from issues common in 
pregnancy (e.g., medical care, physical symptoms, 
and infant’s health) 
X 
Postpartum Stress 
Scale. 
Assesses stressors that may emerge during the 
postpartum period 
X 
Parenting Sense of 
Competence Scale 
Assesses the parent’s sense of competency in 
taking care of their child. 
X 
Unmet basic needs 
Assessment of how confident the women are that 
they can find resources to help them meet their 
basic needs 
X 
Healthy behaviors 
for PPWP. 
We will measure participants’ intent to breastfeed 
using the Infant Feeding Intentions (IFI) scale. 
Contraceptive knowledge and intentions will be 
measured using the Contraceptive Knowledge 
Assessment. 
X 
Daily 
Brief, 3 questions about their confidence in 
maintaining sobriety, having a healthy pregnancy 
and meeting their basic needs. 
Collected within the app 
Weekly 
Assesses struggles in the past week relating to 
drug use, pregnancy and basic needs and if the 
app was useful in addressing these issues. Also 
assesses buprenorphine compliance for past 
week. 
Collected within the app 
 
Qualitative assessments. After 1 week and 1 month (PPWP only) of uMAT-R access, 
participants will be asked to complete 20-30 minute semi-structured interviews with a trained 
interviewer, in-person or virtually (phone call or via Zoom). Participants will be provided the 
option to complete it independently via RedCap link. During the 1 week interview, participants 
will be asked to discuss their experiences with uMAT-R in greater detail, including perceived 
benefits and challenges of participation and suggested modifications to improve specific 
components of uMAT-R. Complications/ technical glitches with the app, reactions to the online 
coaching, how it fared in regard to its ease of understanding, helpfulness,  intuitive flow, 
presentation, pacing, and suggestions for improvement will also be assessed. During the 1 
month interview, PPWP participants will be asked additional questions related to the usability 
and acceptability of uMAT-R, as well as questions related to recovery and other lived 

 
 
 
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experiences related to SUDs and mental health. The  interviews will be conducted in-person, 
over the phone, or via Zoom and will be recorded, and transcribed verbatim for qualitative 
analysis if they are completed with a trained interviewer.  
Research staff will record the interviews view a mobile device (e.g. hand-held recorder, mobile 
phone, or laptop). Video and audio will be collected based on how the interview is conducted 
(i.e., in-person, phone, or Zoom) and data from the recordings will be transcribed. Research 
staff will then immediately save the recording and transcribed interview on a HIPAA approved- 
WUSTL Box or the HIPAA approved-WUSM server. Research staff will immediately delete the 
recording and transcribed interview from the device (with 24 hours of the interview). Recordings 
and transcribed interviews will only be identified by the participants’ designated study ID. 
Recordings will not be attached to any identifiable information. These steps are established as 
best practices by the WUSM Information Security office. 
 

 
 
 
15 
E3 Safety and Adverse Events 
 
3.a 
Safety and Compliance Monitoring 
We go to great lengths to protect the confidentiality of our subjects and are especially sensitive 
to data regarding substance use and substance use-related problems among a particularly 
vulnerable population. 
 
Participant safety: Drs. Szlyk and Cavazos (MPIs), Ms. Zhang, and Ms. Worley will closely 
monitor all coaching interactions with participants. Their combined experiences and 
credentials make them qualified for this role and will ensure participant safety during this 
study. 
 
Additional protections for pregnant women, fetuses, and neonates 
Per Federal regulations: 1) no inducements will be offered to terminate the pregnancy 2) no 
member of the research team will have any part in decisions as to timing, method, or 
procedures used to terminate pregnancy, and 3) no member of the research team will have any 
part in determining the viability of the neonate. 
 
Emotional discomfort: Participants who report discomfort as a result of participation will be 
reminded that their participation is voluntary. They can refuse to answer any questions that they 
are not comfortable with or discontinue the survey assessments/interview at any time. 
 
HIPAA compliance: All project staff will have fulfilled Washington University’s mandatory HIPAA 
training requirements. All aspects of the protocol and study implementation will meet the HIPAA 
requirements specified by the Human Studies Committee and the Privacy Office at Washington 
University. 
Reconnect will host uMAT-R and all data collected within the app. Reconnect has 
partnered with many health care providers to aid in patient addiction recovery, and 
Reconnect is HIPAA compliant. Reconnect will comply with the rules on handling of Protected 
Health Information under the Health Insurance Portability and Accountability Act (“HIPAA”) 
Standards for Privacy of Individually Identifiable Health Information, 45 C.F.R. Part 160 and Part 
164, Subpart E (“Privacy Rule”), the HIPAA Security Standards, 45 C.F.R. Part 160 and Part 
164, Subpart C (“Security Rule”), the HIPAA Breach Notification Regulations, 45 C.F.R. Part 
164, Subpart D (“Breach Notification Rule”), and the federal regulations governing the 
confidentiality and security of substance use disorder information, 42 C.F.R. Part 2 (the “Part 2 
Regulations”) (collectively the “Requirements”). 
 
3.b 
Safety Monitoring 
 
i 
Investigator only 
The MPIs, Drs. Szlyk and Cavazos, will be responsible for routine monitoring of the study 
progress. This monitoring includes scheduled weekly meetings with study staff and review of all 
study-related documentation.  
 
3.c 
Definitions of Adverse Events 
 Coaches and research team members will be trained to monitor for adverse events, including 
Serious Adverse Events (SAEs) would include occurrences that result in death, are life-
threatening, or require hospitalization. The research team  will report any potential adverse events 
immediately upon their identification to the PI. We will also monitor for adverse events at all follow-

 
 
 
16 
up assessments and via all other communication with study participants. Any potentially adverse 
events will be evaluated by the PI within 72 hours. Any SAE will be queried and reported even if it 
appears that the serious unanticipated health event is unrelated to study participation.  
 
3.d 
Data Collection Procedures for Adverse Events 
Adverse event assessment, recording, reporting and investigation will be accomplished through 
structured/standardized assessments, reports from the facilities’ representatives, and self-
reported information provided in the in-app coaching feature. If any information that is disclosed 
indicating potential harm a participant or others within the mobile application and/or the surveys, 
will be disclosed to the facility. The surveys will ask participants questions pertaining to suicidal 
ideation and depression. If the participant answers ‘yes’ to current thoughts of suicide, the 
research team will call the participant as soon as possible to check in and determine if the 
participant needs a handoff to a crisis service. Afterwards, the team will document this phone call 
and notify the participant’s treatment facility. Zhuoran Zhang, Elecia Worley, and other members 
of the e-coaching team (Jordan Michener and Emily Maranets) will follow-up with the participant. 
Zhuoran Zhang has a master’s in experimental psychology and has accumulated valuable clinical 
experience over the course of the year as part of the e-coaching team. Elecia Worley is a 
masters-level social worker with remote and in-person clinical experience from her previous 
positions. Jordan Michener has experiences working with children, adolescents, and adults at a 
behavioral health hospital and holds certificates in Forensic Interviewing and Crisis Intervention. 
Emily Maranets has in-person and remote clinical experience working with a variety of clinical 
populations in both inpatient and outpatient settings. 
 
3.e 
Reporting Procedures 
The PI has ultimate responsibility for ensuring that AEs are detected and reported in a timely 
manner. AEs will be reported to the IRB in accordance with the IRB’s policy. 
 
3.f 
Adverse Event Reporting Period 
A safety report will be generated monthly.  Any AEs will be reported directly to the PI. As 
required by the Washington University IRB, the PI will subsequently report any adverse 
events to the Washington University IRB using methods specified by the IRB. 
 
 
E4 Study Outcome Measurements and Ascertainment 
 
Quantitative measurements: MOUD uptake and adherence, MOUD attitudes, RCC 
engagement, recovery capital, as well as mental health items will be assessed via self-report 
using online Research Electronic Data Capture (REDCap) surveys at baseline. Substance use 
history will also be assessed at baseline via self-report in this way. App usability will be 
assessed at one week also via self-report using online REDCap surveys. REDCap is a secure, 
web-based  application designed to support data capture for research studies. Surveys will be 
formatted for use on either a computer or a mobile device. 
 
Engagement with the uMAT-R app (e.g., number of times logged in, time spent in the app, time 
difference between app log-ins, and number of interactions with the coach) is automatically 
collected within the app platform (Reconnect). 
 
For more information about specific quantitative measurements, see section E2 Schedule of 
Measurements. 
 
Qualitative assessments. Participants will also be asked to complete a 20-30 minute semi- 

 
 
 
17 
structured interview with a trained interviewer after using the uMATR mobile app for 1 week and 
1 month (PPWP only). The  interviews will be conducted in-person, over the phone, or via Zoom 
and will be recorded and transcribed verbatim for qualitative analysis.  
 
F Statistical Plan 
F1 
Sample Size Determination and Power 
 The primary purpose of this study is feasibility. We will receive information on uMAT-R with 64 
PPWP participants; this sample size is feasible to recruit from various treatment facilities, is within 
the range of samples sizes for other pilot tests of digital therapeutics,25-31 and is sufficient for 
data saturation for qualitative interviews.32 
F2 
Interim Monitoring and Early Stopping 
Data that will be reviewed at the routine monitoring meetings include the number and type of 
participants enrolled, that all subjects meet eligibility criteria, the number and reasons for 
exclusions from enrollment, drop-outs and any protocol deviations, the number of participants 
using the app, and that the study is following the IRB-approved protocol. A summary of adverse 
events (AE) and an individual review of serious adverse events (SAE) will also occur in real-time 
as they happen and at these routine monitoring meetings. AEs or SAEs that raise concerns 
(significant change in mood or suicidality) will be immediately reported to the MPIs who will 
determine an appropriate course of action. 
 
To facilitate participant safety, study participants must meet study inclusion and exclusion 
criteria. Once enrolled, follow-up protocols will assess the unanticipated health events at all 
clinic visits and follow-up contacts. Should either excessive risk and/or lack of measurable 
benefit to study participants be determined, the study will be stopped and all participants notified 
in a manner appropriate to the nature of the risk and/or the lack of benefit. 
 
F3 
Analysis Plan 
Quantitative assessments will be recorded using REDCap electronic data capture survey tool. 
REDCap (Research Electronic Data Capture) is a secure, web-based application designed to 
support data capture for research studies. App usability will be examined using descriptive 
measures (mean, standard deviation, median, range) on the efficiency, technical effectiveness, 
and satisfaction components of the USE questionnaire. Descriptive statistics will also be used to 
describe engagement with the app (e.g., median number of log-ins, time spent in the app, 
number of interactions with the coach, etc.), as well as the characteristics of our patient sample 
(demographics, mental health and substance use history). Descriptive statistics will also be 
used to examine MOUD uptake and adherence, MOUD attitudes, RCC engagement, recovery 
capital, pregnancy- and post-partum-related anxiety, confidence in meeting basic needs, and 
opioid or stimulant use within our sample. Team will also employ data science-informed 
approaches for text analyses using message data. Analyses will inform development of a future 
conversational agent to be paired with the mobile intervention. 
Transcripts from interviews will be collected to assist with qualitative data management and 
coding. Inductive thematic analyses will be conducted by two research team members using the 
six steps described by Braun and Clarke33 (getting familiar with the data, creating initial codes, 
looking for themes, reviewing and refining themes, defining and naming themes, producing the 
report). Other pilot studies of apps have used a similar approach to analyze the qualitative 
discussion of app content and/or user experience.26,27 Feedback from the qualitative 

 
 
 
18 
interviews will help to refine app format, content, and coaching for future studies. 
 
G Data Handling and Record Keeping 
G1 Confidentiality and Security 
Information collected in Reconnect (de-identified, aggregate engagement data and survey data 
from in-app assessments) will be downloaded by Reconnect staff, encrypted, and sent to the 
secure Washington University email address of a research team member. Research staff 
members will un-encrypt the data and store it on a dedicated, single-use partition of a server 
under direct control and management by a Washington University IT Specialist. This partition 
is not included as part of the routine server backup, and the data, in whole or in part, will not 
be stored or cached on any external workstations, PCs, or other devices. This partition is not 
shared via networked file systems to other computers. Directory and file access permissions 
on the server are based on user ID and group membership. Each user is assigned a unique 
identification and password string. 
 
G2 Training 
The MPIs, Drs. Szlyk and Cavazos, and Ms. Montayne will be responsible for managing and 
overseeing  the individuals involved with coaching participants in this study. Both Dr. Cavazos 
and Ms. Montayne have years of experience working with individuals struggling with 
substance  use. The MPIs, Drs. Szlyk and Cavazos, will also be responsible for training the 
members of the staff prior to conducting the in-person or remote interviews with participants. 
 
G3 Source Documents 
All interviews will be recorded and transcribed verbatim unless completed via RedCap survey link. 
Transcripts will be removed of all identifiers and only labeled with the Participant’s ID number. We 
will be utilizing the InfoSec approved company Landmark for transcription services (see attached 
email). 
 
 
All other participant assessments will only occur online using REDCap. 
 
G4 Records Retention 
All participant records are stored on a password protected server that is managed by 
Washington University School of Medicine. Only research team members listed on the IRB- 
approved team will have access to study materials. These materials will be stored for at least 
three years as required by the IRB. 
 
H Study Administration 
H1 Organization and Participating Centers 
All study activities will take place at Washington University School of Medicine and consenting 
facilities. 
 
H2 Funding Source and Conflicts of Interest 
This study is funded by NIH & Washington University Psychology Department funds. There are 
no conflicts of interest to declare. 
 

 
 
 
19 
H3 Subject Stipends or Payments 
Participants will be incentivized with gift cards after each survey assessment and will receive an 
additional set of gift cards for their completion of the interview. 
 
 
 
 
 
H4 Study Timetable 
 
Year 
2022 
Quarters 1 
2 
3 
4 

 
 
 
20 
Develop uMAT-R content (daily recovery tips, plain language materials) 
X 
Develop and test new uMAT-R features 
X 
X 
X 
Enroll 64 PPWP participants from various facilities 
X 
X 
Run interviews on uMAT-R 
X 
X 
Data analysis and dissemination of results via papers and presentations 
X 
X 
Refine app content accordingly 
X 
 
I Publication Plan 
Results from this study will provide critical information needed to refine uMAT-R and estimate 
effect sizes to plan a larger-scale, clinical trial that we will propose in next-step NIH  
R mechanisms. Results from this study will disseminated through conference presentations and 
academic journals. Any results published from this study will not contain any participant 
identifiers. 
 
J Attachments 
J1 
Tables 
 
J2 
Informed consent documents 
J3 
Patient education brochures 
J4 
Special procedures protocols 
J5 
Questionnaires or surveys 
K References 
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