Clinical trial NCT06426303: Sex Differences in Trauma, Inflammation and Brain Function and the Implications for Treatment Efficacy in Alcohol Use Disorder
Official title: Sex Differences in Trauma, Inflammation and Brain Function and the Implications for Treatment Efficacy in Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Alcohol Use Disorder
Keywords: Naltrexone
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Portland VA Medical Center
First posted: 2024-05-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this clinical trial is to identify sex-specific biomarkers that confer greater susceptibility for Alcohol Use Disorder (AUD) and differentiate how treatment response varies by sex in people with Alcohol Use Disorder.

The main questions it aims to answer are:

* How does trauma affect emotion regulation, inflammation, and limbic function, and what are the sex-dependent effects of NTX (Naltrexone) on these aspects?
* What is the mechanism of Naltrexone (NTX), and how does it potentially moderate reductions in alcohol use through changes in or interactions between emotion regulation, inflammation, or limbic system function?

Participants will

* Be consented and will undergo comprehensive screening for eligibility criteria
* Complete behavioral assessments and neuropsychological assessments, as well as neurocognitive assessments and neuroimaging measures
* Provide urine samples for a urine drug screen (UDS) and urine pregnancy test (for women), and have blood and a cheek swab collected and stored in the repository
* Take a study drug once daily for 12 weeks and track drug usage and effects in a study journal
* Undergo weekly assessment calls and bi-weekly medical follow-up safety exams

Researchers will compare naltrexone to placebo in AUD to see if naltrexone is effective in reducing alcohol cravings and promoting abstinence.

Researchers will also compare baseline measures between AUD and Healthy Controls.

Detailed description: A twelve-week randomized placebo-controlled trial of naltrexone (NTX) will be conducted in one hundred people with alcohol use disorder (AUD), fifty of which will be women. Fifty healthy participants will serve as controls for baseline measures. We will use validated measures to comprehensively assess trauma exposure including: military sexual trauma (MST), physical or sexual assault, combat exposure, intimate partner violence, and other traumatic events. Emotion regulation will be assessed with the Cognitive Emotion Regulation questionnaire and Difficulty in Emotion Regulation scale. Functional magnetic resonance imaging at rest and during an emotion regulation task will assess limbic system connectivity and reactivity. Inflammation will be indexed with a multiplex panel assay of peripheral inflammatory markers. Days of alcohol use and average weekly standard drinks will be assessed at each time-point.

Eligibility criteria: Inclusion Criteria:

* 18-60 years old
* Veteran enrolled in VHA healthcare

Alcohol Group:

* must meet diagnosis for recent alcohol-use disorder (DSM-V)
* willing to return for follow-up visits and can participate for 12-weeks

Control Group:

* must not meet DSM-V criteria for a use disorder other than nicotine

Exclusion Criteria:

* Clinically significant neurological, endocrine, hepatic, or systemic disease that would compromise safe participation or confound outcomes
* Left-handedness
* Axis-1 psychiatric diagnoses other than anxiety, depression or post-traumatic stress disorder
* Recreational or prescriptive use of psychotropic medications
* Recreational or prescriptive use of opioid medications or have a past or current history of abuse or dependence on opioids
* MRI contraindications (e.g. metal in body)
* Positive urine drug screen, except for nicotine and marijuana, on test days
* Women who are pregnant or breastfeeding
* Participants on hormonal therapy or treatments other than pregnancy contraceptives
* Autoimmune or neurodegenerative diseases that present with neuroinflammation (multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's, Parkinson's)
* Current participation in an investigational drug study
* Alcohol group: \< 5 days and \> 3 weeks of abstinence from alcohol
* Alcohol group: Liver disease requiring medication or medical treatment, and/or aspartate or alanine aminotransferase levels greater than 3 times the upper limit of normal, gastrointestinal or renal disease that would significantly impair absorption, metabolism or excretion of study drug, or require medical treatment.
* Non-english speaker

Primary outcomes:
measure: Change from baseline in alcohol use (number of drinking days, amount used per day)
timeFrame: Baseline and Week 12
measure: Changes from baseline in peripheral immune biomarkers associated with inflammation
timeFrame: Baseline and Week 12
measure: Changes in limbic functional connectivity
timeFrame: Baseline and Week 12
measure: Changes from baseline in BOLD signal brain activation during an emotion regulation fMRI task
timeFrame: Baseline and Week 12
measure: Changes from baseline in emotion regulation assessed with the Difficulty in Emotion Regulation Scale (DERS)
timeFrame: Baseline and Week 12
measure: Changes from baseline in emotion regulation assessed with the Cognitive Emotion Regulation Questionnaire (CERQ)
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change from baseline in craving (include craving measures/questionnaires)
timeFrame: Baseline and Week 12
measure: Differences in baseline trauma exposure (composite score)
timeFrame: Baseline and Week 12
measure: Change from baseline in neuropsychological testing scores
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Portland
country: United States
facility: VA Portland Health Care System
state: Oregon
Study officials:
References: