A Mobile Executive Functioning Intervention for Momentary Craving in Opioid Use Disorders
Phase: NA
Conditions: Opioid Use Disorder
Sponsor: Mclean Hospital

 
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Study Protocol and Statistical Analysis Plan 
 
Study Title: 
Developing a Working Memory Intervention for Craving in Opioid 
Use Disorder 
 
Date: 9/9/2021 
NCT#: NCT05086835 
 
 
 

 
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Protocol Title: Developing a Working Memory Intervention for Craving in Opioid Use Disorder 
 
I. Background and Significance 
 
Even when treated with methadone or buprenorphine maintenance, many people with opioid 
use disorder (OUD) continue to experience craving. Among both users of heroin and users of 
prescription opioids, mounting evidence shows that craving predicts return to use and 
undermines existing treatments for OUD, thus, the development of new interventions to reduce 
craving is a priority for addressing the opioid crisis (NIH HEAL Initiative Research Plan, 2019). 
Deficits in executive functioning, particularly working memory, are a central mechanism that 
undermines the ability to inhibit craving. Laboratory studies in non-clinical samples show that 
engaging in working memory tasks before or during a craving induction increases the ability to 
resist craving. This suggests that people with OUD may benefit from engaging in working 
memory tasks at the specific moment when craving occurs. Although previous research shows 
that working memory “training” does not improve clinical outcomes in OUD (Wiers, 2018), these 
studies have not delivered training at the moment that craving actually occurs in daily life. Thus, 
engaging in working memory tasks at the moment that craving occurs could presumably help 
individuals with OUD to manage this persistent symptom, but this has not been tested. Further, 
studies using Ecological Momentary Assessment (EMA) methods show that people with OUD 
can accurately track moment-to-moment fluctuations in craving in their daily lives (Preston et al., 
2017), suggesting that it may be feasible to deliver interventions for craving in the moment when 
craving is reported. These converging lines of evidence indicate that it may be feasible to use a 
smartphone-based digital health intervention to help individuals with OUD manage craving in 
their daily lives, through the use of a mobile working memory intervention. 
However, before such interventions can be tested, it is essential to collaborate with 
individuals who would actually use the intervention – adults with OUD – to gather their feedback 
on the parameters of this type of intervention. This process, often referred to as human-
centered design (Yardley et al., 2015), involves collaborating with stakeholders to gauge their 
perceptions of the intervention, collect qualitative data on their impressions of what features of 
the intervention would be most helpful for the target symptom (craving), and provide an 
opportunity for stakeholders to suggest ways to make the intervention more credible, helpful, 
and engaging. Indeed, these three domains are significant predictors of ultimate engagement in 
digital interventions (Yardley et al., 2016). Thus, the goal of the human-centered design process 
in this study is to increase the likelihood that the final intervention will be relevant and useful for 
individuals with OUD. 
Using the NIH Stage Model of Intervention Development, this study will consist of a Stage 
1A project designed to gather feedback from adults receiving treatments for OUD (n = 20). This 
feedback will help our research team finalize a working memory intervention in preparation for a 
future Stage 1B trial using a randomized design. 
 
II. Specific Aims 
 
Objective #1: Assess attitudes about mobile health interventions in adults with opioid use 
disorders. 
 
Objective #2: Collect feedback from participants regarding their perceptions of proposed 
components for an intervention to address craving in opioid use disorder. 
 
Objective #3: Based on feedback from participants, refine proposed components for the 
development of a smartphone application to be used in a future study. 

 
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This study does not involve formal hypothesis testing; rather, the goal is to gain user input to 
inform the final development of a smartphone-based working memory intervention for opioid 
craving. 
 
III. Subject Selection 
 
Up to 25 participants will be recruited for the present study. We aim to have complete data 
for 20 participants, but will recruit up to 25 in order to allow for the possibility that some 
participants may drop out or be found ineligible after consenting to participation. Recruitment will 
take place at McLean Hospital’s programs that provide treatment for opioid use disorder, 
including the Naukeag residential treatment program and the Alcohol, Drug, and Addiction 
Treatment Program (ADATP) at the main campus of McLean Hospital. Inclusion criteria include: 
a diagnosis of opioid use disorder, self-reported ability to use a smartphone, and age 18 or 
greater. Exclusion criteria include: lack of capacity to consent; current involuntary admission (for 
inpatients); acute psychosis; diagnosis of a neurological disorder or other brain disease 
affecting cognitive functioning; history of stroke; or cognitive deficits indicated by a score of less 
than 26 on the Montreal Cognitive Assessment (MoCA; Nasreddine et al., 2005). Other than the 
MoCA, all exclusion criteria will be evaluated through a review of a participants’ medical record 
and consultation with clinical staff. 
Potential participants will be enter the study through two pathways: (1) self-selection based 
on posted advertisements and presentations by research staff at the beginning of clinical 
groups, or (2) invitation to participate from research staff, after introduction by a clinical staff 
member and the patient’s agreement to meet with the Research Assistant. Regarding this 
second pathway, potential participants are identified via either (1) review of the electronic 
medical record of new admissions, or (2) referral from clinical staff. Prior to approaching any 
potential participants, a member of study staff will consult with the patient’s treatment team to 
verify that they do not meet any exclusion criteria (e.g., for inpatients, that they are not 
hospitalized involuntarily), and to verify that the potential participant has been determined by the 
treatment team to have the capacity to consent. Once a potential participant is identified, a 
member of the study team (research assistant or PI) will be introduced to the potential 
participant by a member of the clinical staff. The study staff member will then meet in-person 
with the participant to provide a brief overview of the study. If the potential participant continues 
to express interest, a study session will be scheduled at the participant’s convenience. 
 
IV. Subject Enrollment 
 
Participants will review the study fact sheet, provide verbal consent, and complete all study 
procedures in one study session lasting approximately one hour. If participants would like extra 
time to review the study fact sheet before deciding to participate, they may do so. Consent will 
be obtained via a review of the study fact sheet and discussion of study procedures immediately 
prior to the study session. A member of study staff (research assistant or PI) will meet with the 
participant to review the study fact sheet, answer questions about the study, and verbally 
explain study procedures. Participants may choose to verbally consent and begin participation, 
or they may choose to take a blank copy of the study fact sheet with them and to consider 
enrolling at a later date. There is no time limit on how long participants may choose to consider 
participation; however, participants will only be eligible to enroll in the study if they are still 
receiving treatment in one of the recruitment sites at McLean. Research staff will document that 
verbal consent was obtained, and will record participants’ name and date of consent in a study-
specific electronic database.  
 

 
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Participants will be fully informed of the nature of the risks involved during the informed 
consent process and will have the ability to discontinue and withdraw consent at any time 
without penalty. All study personnel will be trained in the appropriate care of human participants 
and will have completed the Collaborative Institutional Training Initiative (CITI) human subjects 
training, and research assistants will be closely supervised by the study PI. As part of the 
informed consent process, participants will be informed that if they feel uncomfortable 
responding to any question, they are free to choose not to respond or to express their 
discomfort.  
 
V. Study Procedures 
 
All study procedures will be conducted in a single study session lasting approximately one 
hour. In all sessions, participants will meet with members of study staff to review the informed 
consent fact sheet, complete brief assessment of cognitive functioning to verify eligibility (the 
MoCA), and then complete a qualitative interview to inform intervention development. 
Participants who complete this study will complete interviews that encompass the planning and 
design phases of intervention development. These interviews will assess their perceptions of 
smartphone-based interventions in general; their perceptions of smartphone-based 
interventions for substance use disorders; their existing strategies for managing craving in daily 
life; and their attitudes about the potential features of the working memory intervention for 
craving that is being developed.  
Participants who complete this study will also provide feedback on specific components of 
the intervention being developed. To aid this goal, participants will view wireframes (non-
functional mockups) of different intervention components, will try using “demonstration” versions 
of various app components using a study-specific iPod, and will be asked to provide feedback in 
response to various prompts about the acceptability of these components (e.g., clarity of 
instructions, flow from one screen to the next, presentation of feedback, etc). The intervention 
being developed is a working memory task that is based on a modified version of the game 
“Tetris,” (or something similar to Tetris) which involves using visual-spatial memory to organize 
falling blocks. App components that participants will try out include the freely available game 
“Tetris” (https://apps.apple.com/us/app/tetris/id1491074310) and various games contained in an 
app called “mindLAMP” (https://docs.lamp.digital/privacy). Both apps involve short (1-2 minute) 
games that involve using working memory. Thus, we will ask participants about their 
perceptions of using a game like this for treatment of craving, their previous experience using 
this type of game, and the degree to which they would choose to use this type of intervention 
when experiencing opioid craving. At the conclusion of the study session, all participants will 
complete self-report measures of demographic information, perceptions of questions that 
assess craving on smartphones, and a self-report measure of task acceptability(a modified 
Credibility and Expectancy Questionnaire; Devilly et al., 2000). This self-report measure will 
include additional questions to assess perceived helpfulness and enjoyability of the intervention 
and will be administered electronically via REDCap (Harris et al., 2009). At the conclusion of the 
study visit, participants will be provided with one $25 gift card for their participation.  
Measures to be used in this study include: 
a. Montreal Assessment of Cognitive Functioning (MoCA) 
b. Qualitative interview of craving, mobile interventions, and intervention feedback 
c. Modified Credibility and Expectancy Questionnaire 
d. Demographic Questionnaire 
e. Daily Questions Survey 
 
VI. Biostatistical Analysis 
 

 
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Variables collected as part of this study include: responses to open-ended questions 
collected as part of a qualitative interview (written down on a study-specific interview form), 
questionnaire data (collected electronically via REDCap; Harris et al., 2009), and results of the 
brief cognitive assessment (MoCA; conducted on pen and paper and recorded electronically). 
We will not analyze data from the demonstration apps. Formal statistical tests of hypotheses will 
not be conducted as part of this study, as the goal is to collect participant feedback to inform the 
development of a future smartphone-based intervention. Themes arising from qualitative data 
may be aggregated and summarized using a basic coding method such as the general inductive 
approach (Thomas, 2006). Descriptive statistics will be generated from survey data to 
characterize the distribution of scores on these measures. 
 
VII. 
Risks and Discomforts 
 
The anticipated risks associated with the proposed study are minimal. There is the 
potential for some subjects to experience discomfort in discussing psychiatric symptoms, 
including discussing craving for opioids. Participants will be reminded that they can choose to 
decline to answer any questions they do not wish to answer during the qualitative interviews, 
and will be reminded of the voluntary nature of study participation.  
Another potential risk is a breach of confidentiality. However, as with the other risks mentioned 
above, we will take precautions to protect against this risk. Participants’ names and other 
identifying information will be stored separately from other study materials, on a password-
protected database. All other study materials (e.g., interview notes, self-report measures) will 
use a study ID number rather than identifying information, with the exception of the mobile apps: 
we will not enter any participant-specific information into the demonstration apps. 
 
Participants will be fully informed of the nature of the risks involved during the informed 
consent process and will have the ability to discontinue and withdraw consent at any time. As 
part of the informed consent process, participants will be informed that if they feel uncomfortable 
responding to any question they are free to choose not to respond or to express their 
discomfort.  Each participant will be made aware that participation is completely voluntary and 
that he or she may withdraw participation at any time without penalty. All study personnel will be 
trained in the appropriate care of human participants, will have completed Collaborative 
Institutional Training Initiative (CITI) program and will be closely supervised by the study PI.  If a 
participant experiences distress at a higher level or longer duration than the mild to moderate, 
transient distress anticipated in study procedures, the PI will be contacted to determine whether 
intervention is indicated.   
 
VIII. 
Potential Benefits 
 
Participants are not expected to derive any direct benefit from this study. However, 
participation in this study will directly inform the development and finalization of an intervention 
to be tested in a future clinical trial. Assessment of participants’ own lived experience of opioid 
use disorders, including craving, is essential to developing appropriate interventions for those 
with opioid use disorders. Thus, this study has the potential to improve future treatments for 
opioid craving. 
 
IX. 
Monitoring and Quality Assurance 
 
Dr. Peckham (a licensed clinical psychologist) will be responsible for continuous monitoring 
of the data and safety of subjects in the study. He will consult with other senior members of the 
study team (including Dr. Weiss – Chief of the Division of Alcohol, Drugs, and Addiction; and Dr. 

 
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McHugh, psychologist in the Division of Alcohol, Drugs, and Addiction) when any specific safety 
concerns arise. Dr. Peckham will monitor all survey and interview data as it is collected and will 
alert the IRB of any safety issues; minor deviations will be reported at annual continuing review 
in accordance with IRB guidelines. 
 
X. 
References 
 
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questionnaire. Journal of Behavior Therapy and Experimental Psychiatry, 31(2), 73–86. 
https://doi.org/10.1016/S0005-7916(00)00012-4 
 
Harris, P. A., Taylor, R., Thielke, R., Payne, J., Gonzalez, N., & Conde, J. G. (2009). Research 
electronic data capture (REDCap)-A metadata-driven methodology and workflow process for 
providing translational research informatics support. Journal of Biomedical Informatics, 42(2), 
377–381. https://doi.org/10.1016/j.jbi.2008.08.010 
 
National Institutes of Health NIH HEAL Initiative Research. (March 18th, 2020). Retrieved from: 
https://heal.nih.gov/about/research-plan  
 
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