Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06426303
Other study ID # 25536
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date June 1, 2024
Est. completion date December 31, 2028

Study information

Verified date May 2024
Source Oregon Health and Science University
Contact Jazryn Nagum
Phone 503-721-7964
Email vhaporhoffmanlab@va.gov
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 100
Est. completion date December 31, 2028
Est. primary completion date December 31, 2028
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 60 Years
Eligibility 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

Study Design


Intervention

Drug:
Naltrexone
12-week randomized double blinded placebo-controlled drug trial titrating drug/placebo dose after 1 week.

Locations

Country Name City State
United States VA Portland Health Care System Portland Oregon

Sponsors (2)

Lead Sponsor Collaborator
Milky Kohno Portland VA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change from baseline in alcohol use (number of drinking days, amount used per day) Drinking days and average number of weekly standard drinks will be measured at baseline and at follow-up Baseline and Week 12
Primary Changes from baseline in peripheral immune biomarkers associated with inflammation Plasma samples will be analyzed using a customized, high-sensitivity magnetic bead multiplex assay Luminex system. Samples will be prepared and analyzed to measure peripheral immune markers: interleukin (IL)-1-beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, brain-derived neurotrophic factor (BDNF), monocyte chemotactic protein (MCP)-1 and neural cell adhesion molecule (NCAM). Intra-and inter-assay coefficients of variation, as indices of within-and between-assay precision, respectively, will be calculated to examine the reliability of cytokine measurements. Baseline and Week 12
Primary Changes in limbic functional connectivity Resting-state functional magnetic resonance imaging (rs-fMRI) will be used to assess changes in limbic system connectivity. Correlation coefficients of low-frequency oscillations in the fMRI blood oxygenation level dependent (BOLD) signal between regions and between large-scale resting-state networks in the brain will be z-score transformed. A score of 0 indicates no change while higher or lower scores indicate increased or decreased connectivity, respectively. Baseline and Week 12
Primary Changes from baseline in BOLD signal brain activation during an emotion regulation fMRI task The task will assess emotional reactivity and regulation to negative and stressful images. Each event (cue, neutral-look, negative-look, negative-reappraise and rating scale of negative affect) will be modeled using a canonical hemodynamic response function with a time derivative. The contrasts of interest will be Negative-look vs Neutral-look and Negative-look vs Negative-reappraise. Amygdala BOLD signal estimates will be extracted to calculate percent-change. Baseline and Week 12
Primary Changes from baseline in emotion regulation assessed with the Difficulty in Emotion Regulation Scale (DERS) DERS is a 36-item self-report questionnaire scored on a 5-point scale from 1 (almost never) to 5 (almost always), with total score ranging from 36 to 180. It measures emotion regulation difficulties across six dimensions: 1. Non-acceptance of emotional responses, 2. Difficulties engaging in goal-directed behavior, 3. Impulse control difficulties, 4. Lack of emotional awareness, 5. Limited access to effective emotion regulation strategies, 6. Lack of emotional clarity. Higher scores suggest greater difficulties in emotion regulation. Baseline and Week 12
Primary Changes from baseline in emotion regulation assessed with the Cognitive Emotion Regulation Questionnaire (CERQ) CERQ is a 36-item self-report questionnaire that identifies cognitive emotion regulation or cognitive coping strategies used after having experienced negative events or situations. Scores can identify individual strategies to compare with normed scores from various populations. The nine cognitive emotion regulation strategies are measured on a 5-point Likert scale ranging from 1 to 5, with scores being obtained by calculating the mean scores belonging to a particular subscale. Higher subscale scores indicate greater use of a specific cognitive strategy. Baseline and Week 12
Secondary Change from baseline in craving (include craving measures/questionnaires) The Brief Alcohol Craving Scale, a 10-item self-report assessment of craving, will be used. Participants will be prompted with a statement regarding alcohol cravings and will choose an answer ranging between "strongly disagree" and "strongly agree." Baseline and Week 12
Secondary Differences in baseline trauma exposure (composite score) Department of Veterans Affairs Military Sexual Trauma Screening consists of two questions used nationally within the Veterans Heath Administration (VHA) to screen for MST. Response options are yes, no, or decline to respond.
Trauma Assessment for Adults (TAA) is a 17-item self-report on combat exposure, physical or sexual assault, surviving serious accidents and other threatening life events.
Life Stressor Checklist-Revised (LSC-R) includes self-report measures relevant to women such as abortion or caregiver duties, in addition to 30 life events related to natural disasters, physical or sexual assault, death of a relative, incarceration and financial hardships.
Childhood Maltreatment questionnaire is 70 items in five dimensions: emotional, physical, and sexual abuse, and physical and emotional neglect. A 7-point scale will be used to indicate level of trauma
Baseline and Week 12
Secondary Change from baseline in neuropsychological testing scores The Standard Neuropsychological Battery will be used Baseline and Week 12
See also
  Status Clinical Trial Phase
Recruiting NCT04788004 - Long-term Recovery: Longitudinal Study of Neuro-behavioral Markers of Recovery and Precipitants of Relapse
Recruiting NCT05684094 - Mechanisms of Risky Alcohol Use in Young Adults: Linking Sleep to Reward- and Stress-Related Brain Function N/A
Completed NCT03406039 - Testing the Efficacy of an Online Integrated Treatment for Comorbid Alcohol Misuse and Emotional Problems N/A
Completed NCT03573167 - Mobile Phone-Based Motivational Interviewing in Kenya N/A
Completed NCT04817410 - ED Initiated Oral Naltrexone for AUD Phase 1
Active, not recruiting NCT04267692 - Harm Reduction Talking Circles for American Indians and Alaska Natives With Alcohol Use Disorders N/A
Completed NCT03872128 - The Role of Neuroactive Steroids in Stress, Alcohol Craving and Alcohol Use in Alcohol Use Disorders Phase 1
Completed NCT02989662 - INIA Stress and Chronic Alcohol Interactions: Glucocorticoid Antagonists in Heavy Drinkers Phase 1/Phase 2
Recruiting NCT06030154 - Amplification of Positivity for Alcohol Use N/A
Active, not recruiting NCT05419128 - Family-focused vs. Drinker-focused Smartphone Interventions to Reduce Drinking-related Consequences of COVID-19 N/A
Completed NCT04564807 - Testing an Online Insomnia Intervention N/A
Completed NCT04284813 - Families With Substance Use and Psychosis: A Pilot Study N/A
Completed NCT04203966 - Mental Health and Well-being of People Who Seek Help From Their Member of Parliament
Recruiting NCT05861843 - Craving Assessment in Patients With Alcohol Use Disorder Using Virtual Reality Exposure
Terminated NCT04404712 - FAAH Availability in Psychiatric Disorders: A PET Study Early Phase 1
Enrolling by invitation NCT04128761 - Decreasing the Temporal Window in Individuals With Alcohol Use Disorder N/A
Not yet recruiting NCT06444243 - Psilocybin-assisted Therapy for Alcohol Use Disorder Phase 2
Not yet recruiting NCT06163651 - Evaluating a One-Year Version of the Parent-Child Assistance Program N/A
Not yet recruiting NCT06337721 - Preventing Alcohol Use Disorders and Alcohol-Related Harms in Pacific Islander Young Adults N/A
Enrolling by invitation NCT02544581 - Preliminary Analysis of the Soberlink Alcohol Breath Analyzer System's (SABA) Clinical Utility During Aftercare N/A