- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06410196
Mood and Decision-making in Methamphetamine Use Disorder (MDM-MUD)
Modulating Explore-exploit Biases by Improving Mood in Adults With Methamphetamine Use Disorder
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The growing epidemic of methamphetamine use disorder (MUD) is a significant burden on public health with surging overdose deaths, high likelihood of relapse, and current lack of approved medication to treat the disorder. When it comes to decision-making, individuals with MUD often prioritize drug over non-drug rewards despite negative life consequences; in addition, they may not sufficiently "explore" all available choices to "exploit" the best one (in other words, make the optimal choice leading to positive consequences). Therefore, the "explore-exploit" trade-off is often dysfunctional in MUD. Decision-making imbalances in the explore-exploit trade-off may extend well into abstinence, a period marked by a negative affective state (low mood, high depression and anxiety, withdrawal), which in turn triggers heightened craving and subsequent drug use urges. The insula, anterior cingulate cortex and striatum are crucial brain regions involved in explore-exploit behaviors and affective state signaling that have also been linked to drug reward processing in MUD. We propose that reducing negative affective state (improving mood) could help normalize explore-exploit behaviors and the response of these brain areas in individuals currently abstinent from methamphetamine and other drugs. This project will use a non-drug-related autobiographical memory recall to improve the mood of individuals with MUD and measure whether it normalizes non-drug decision-making, using a functional magnetic resonance imaging-based 3-arm bandit task and a behavioral contextual reinforcement learning task. A mixed experimental design in n=80 (72 completers, assuming 10% attrition) allows the identification of a between-subjects effect of positive (n=40, 36 completers) vs. neutral (n=40, 36 completers) mood modulation and assess the within-subject impact on explore-exploit behaviors pre- versus post-mood modulation. Mood groups will be compared on positive and negative affect, and behavioral/brain responses to reward valuation, outcomes and learning rates.
The overarching goal is to establish that improving mood in individuals with MUD can reduce their negative affective state, normalize outcome sensitivity in key brain regions and associated learning, and reduce the influence of drug rewards on the valuation of non-drug rewards. This approach of this proposal embodies the goals of the NIH RDoC Initiative and the NeuroMAP Center by identifying an actionable disease-modifying target (mood) and studying its effect on the cognitive and neural dysfunction underlying a specific cognitive process (explore-exploit behaviors) relevant to MUD, and possibly other related neuropsychiatric disorders. By targeting the intertwined mechanisms between negative affect and explore-exploit biases, innovative, effective intervention strategies for MUD may be unveiled, addressing a critical public health challenge.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Maëlle CM Gueguen, PhD
- Phone Number: 918-502-5155
- Email: mgueguen@laureateinstitute.org
Study Locations
-
-
Oklahoma
-
Tulsa, Oklahoma, United States, 74136
- Laureate Institute for Brain Research
-
Contact:
- Maëlle CM Gueguen, PhD
- Phone Number: 918-502-5155
- Email: mgueguen@laureateinstitute.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Adults 18-65 years old
- English proficiency as evaluated by language ability during screening
- Past-year diagnosis of DSM-5 methamphetamine use disorder (MUD) confirmed by the MINI
- Actively enrolled in treatment for substance use disorder.
Exclusion Criteria:
- Severe traumatic brain injury (as indicated by a score ≥3 on the Tulsa Head Injury Screen
- Any medical condition interfering with the participation in the study as determined by medical screening
- DSM-5 diagnosis of psychotic disorders, bipolar I disorder, or major depressive disorder with psychosis
- fMRI contraindications as listed on the MR environment screening form
- Positive breathalyzer for alcohol
- Positive urine drug screening, except for cannabis or prescribed benzodiazepines, as indicated in the medical screening
- Evidence of inability to comply with study procedures based on judgement of the experimenter.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Positive mood modulation
Use of happy/positive autobiographical memories which are vivid, emotionally pleasurable and not drug-related, as assessed by individual interview and ratings
|
Autobiographical memory recall designed to modulate mood and affective state by reminiscing about personal life events
Other Names:
|
Sham Comparator: Neutral mood modulation
Use of neutral/procedural autobiographical memories which are vivid, emotionally neutral and not drug-related, as assessed by individual interview and ratings
|
Autobiographical memory recall designed to modulate mood and affective state by reminiscing about personal life events
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Current affective state
Time Frame: Change from pre-intervention (baseline) to post-intervention (90min later) on study day 1
|
Use of PANAS-PA and PANAS-NA questionnaires to measure positive and negative affect respectively (scale range: 0=low; 60=high; low mood is defined as low positive and/or high negative affect)
|
Change from pre-intervention (baseline) to post-intervention (90min later) on study day 1
|
Learning rates
Time Frame: Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
|
Computational modeling is used to compute how fast (learning rate) participants update their choice strategy following appetitive and aversive outcomes during 3-arm bandit task
|
Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
|
Response to punishment in insular cortex
Time Frame: Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
|
BOLD signal is used to measure the activity in the insula as a predefined region of interest (ROI), using Brainnetome atlas, following the delivery of aversive outcomes during 3-arm bandit task
|
Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
|
Correct choice rate of mid-value option in contexts 1 (M1) and 2 (M2) during the testing phase
Time Frame: Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
|
Proportion of trials for which the mid-value option is correctly chosen when paired against a high- or low-value option during contextual RL task
|
Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
|
∆BIC for absolute vs. relative value coding
Time Frame: Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
|
Difference in model-fitting between the absolute and intrinsically enhanced or range adaptive (relative) models as measured by Bayesian Information Criterion (∆BIC) during contextual RL task
|
Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response to punishment in anterior cingulate cortex (ACC)
Time Frame: Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
|
BOLD signal is used to measure the activity in the ACC as a predefined ROI, using Brainnetome atlas, following the delivery of aversive outcomes during 3-arm bandit task
|
Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
|
Response to punishment in striatum
Time Frame: Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
|
BOLD signal is used to measure the activity in the striatum as a predefined ROI, using Brainnetome atlas, following the delivery of aversive outcomes during 3-arm bandit task
|
Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
|
Influence of abstinence duration on value coding
Time Frame: Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
|
Across participants, correlation of number of days since last use of amphetamine with ∆BIC during contextual RL task
|
Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
|
Influence of craving on value coding
Time Frame: Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
|
Across participants, correlation of intensity of craving for amphetamine with ∆BIC during contextual RL task
|
Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
|
Influence of withdrawal on value coding
Time Frame: Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
|
Across participants, correlation of intensity of withdrawal for amphetamine with ∆BIC during contextual RL task
|
Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Maelle Gueguen, PhD, Laureate Institute for Brain Research, Inc.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 2024-002
- P20GM121312 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Methamphetamine Abuse
-
National Institute on Drug Abuse (NIDA)Not yet recruitingMethamphetamine-dependence | Methamphetamine Abuse
-
InterveXion Therapeutics, LLCNational Institute on Drug Abuse (NIDA)CompletedMethamphetamine-dependence | Methamphetamine AbuseUnited States
-
Centre for Addiction and Mental HealthNot yet recruitingMethamphetamine-dependence | Methamphetamine AbuseCanada
-
InterveXion Therapeutics, LLCNational Institute on Drug Abuse (NIDA)TerminatedMethamphetamine-dependence | Methamphetamine AbuseUnited States
-
University of KentuckyNational Institute on Drug Abuse (NIDA)CompletedMethamphetamine Dependence | Methamphetamine AbuseUnited States
-
University of California, Los AngelesNational Institute on Drug Abuse (NIDA)TerminatedMethamphetamine Dependence | Methamphetamine AbuseUnited States
-
University of CincinnatiNational Institute on Drug Abuse (NIDA)CompletedMethamphetamine Dependence | Methamphetamine AbuseUnited States, Canada
-
University of KentuckyNational Institute on Drug Abuse (NIDA)CompletedMethamphetamine Dependence | Methamphetamine AbuseUnited States
-
Oregon Health and Science UniversityOregon Health Authority; Comagine HealthRecruitingMethamphetamine AbuseUnited States
-
Assiut UniversityNot yet recruitingMethamphetamine Abuse
Clinical Trials on Mood modulation
-
Massachusetts General HospitalNutrition and Obesity Research Center at Harvard (NORC-H)Terminated
-
Centre for Addiction and Mental HealthNational Institute of Mental Health (NIMH); University of Alabama at Birmingham and other collaboratorsRecruiting
-
Lawrence UniversityCompletedSelf-Injurious Behavior | Depression, AnxietyUnited States
-
University of MichiganRecruitingDepression | Mood Disorders | Stress | Anxiety | Mental Health Wellness 1United States
-
Thync Global, Inc.ethica Clinical Research Inc.UnknownPlaque PsoriasisUnited States
-
Northwestern UniversityActive, not recruitingCerebral Palsy | Diplegic Cerebral Palsy | Bilateral Cerebral PalsyUnited States
-
Universitätsklinikum Hamburg-EppendorfCompleted
-
Cantonal Hospital of St. GallenCompletedConstipation | Fecal Incontinence
-
University of Wisconsin, MadisonCompletedHealthyUnited States