Sex Differences in Trauma, Inflammation and Brain Function and the Implications for Treatment Efficacy in Alcohol Use Disorder (ABSTAIN)

Milky Kohno

Status and phase: Enrolling; Phase 4

Conditions: Alcohol Use Disorder

Treatments: Drug: Naltrexone

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT06426303

25536

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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100 participants in 2 patient groups

Alcohol Use Disorder (AUD)

Experimental group

Description:

Drug: Naltrexone Half of the study participants with AUD will take an oral tablet of 50 mg naltrexone once daily for one week followed by 11 weeks of 100 mg naltrexone orally, once daily. Drug: Placebo oral tablet The other half of study participants will receive an identical looking placebo in tablet form and take the medication using an identical schedule as the real drug. Drug type will be randomized.

Treatment:

Drug: Naltrexone

Healthy Controls

No Intervention group

Description:

Baseline measures will be taken but controls will not continue to the drug trial.