Clinical trial NCT06410196: Mood and Decision-making in Methamphetamine Use Disorder
Official title: Modulating Explore-exploit Biases by Improving Mood in Adults With Methamphetamine Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Methamphetamine Abuse
Lead sponsor: Laureate Institute for Brain Research, Inc.
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
First posted: 2024-05-13
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 80 participants to be enrolled in the study, with 40 in each arm (randomized arm allocation)
Primary purpose: BASIC_SCIENCE

Brief summary: In this project, the investigators examine behavior and associated brain activity during explore-exploit decision-making tasks performed pre- and post-modulation of affective state using autobiographical memory recall. The investigators hypothesize that a positive memory recall will reduce negative affective state, reduce explore-exploit biases and normalize the associated brain activity. The investigators propose a randomized double-blind, sham-controlled trial of positive autobiographical memory recall with 80 adults (n=40 per arm) with methamphetamine use disorder (MUD) currently involved in abstinence only treatment centers.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Current affective state
timeFrame: Change from pre-intervention (baseline) to post-intervention (90min later) on study day 1
measure: Learning rates
timeFrame: Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
measure: Response to punishment in insular cortex
timeFrame: Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
measure: Correct choice rate of mid-value option in contexts 1 (M1) and 2 (M2) during the testing phase
timeFrame: Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
measure: ∆BIC for absolute vs. relative value coding
timeFrame: Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
Secondary outcomes:
measure: Response to punishment in anterior cingulate cortex (ACC)
timeFrame: Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
measure: Response to punishment in striatum
timeFrame: Change from pre-intervention (baseline) to post-intervention (30min later) on study day 1
measure: Influence of abstinence duration on value coding
timeFrame: Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
measure: Influence of craving on value coding
timeFrame: Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
measure: Influence of withdrawal on value coding
timeFrame: Change from pre-intervention (baseline) to post-intervention (60min later) on study day 1
Other outcomes:
Locations:
city: Tulsa
country: United States
facility: Laureate Institute for Brain Research
state: Oklahoma
Study officials:
affiliation: Laureate Institute for Brain Research, Inc.
name: Maelle Gueguen, PhD
role: PRINCIPAL_INVESTIGATOR
References: