Alcohol Use DisorderPhase 4ABSTAINNCT06426303
Sex Differences in Trauma, Inflammation and Brain Function and the Implications for Treatment Efficacy in Alcohol Use Disorder
A Phase 4 study testing Naltrexone in people with Alcohol Use Disorder, run by Milky Kohno at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Naltrexone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 2 May 2024to 31 Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
VA Portland Health Care System
Portland, Oregon, 97239
Jazryn Nagum, 503-721-7964, vhaporhoffmanlab@va.gov
About this study
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:
Read more
- 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.
Read the 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.
- Conditions
- Alcohol Use Disorder
- Being tested
- Naltrexone
- Keywords
- Naltrexone
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaltrexoneDrug
Also called Revia
12-week randomized double blinded placebo-controlled drug trial titrating drug/placebo dose after 1 week.
| Study group | Role | What they receive |
|---|---|---|
| Alcohol Use Disorder (AUD) | Experimental | 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. Receives: Drug: Naltrexone |
| Healthy Controls | No intervention | Baseline measures will be taken but controls will not continue to the drug trial. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
Secondary outcomes (3)
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."
Measured: Baseline and Week 12
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
Measured: Baseline and Week 12
Change from baseline in neuropsychological testing scores
The Standard Neuropsychological Battery will be used
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2024
- Study start2 May 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Milky Kohno
- Sponsor type
- University, hospital or other
- Collaborators
- Portland VA Medical Center
- Responsible party
- Sponsor-investigator, Milky Kohno, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06426303
- Sponsor's protocol ID
- 25536
- Acronym
- ABSTAIN
- Status last verified
- Oct 2026
- First submitted
- 19 Apr 2024
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sex Differences in Trauma, Inflammation and Brain Function and the Implications for Treatment Efficacy in Alcohol Use Disorder
- ClinicalTrials.gov ID
- NCT06426303
- Acronym / sponsor ID
- ABSTAIN / 25536
- Conditions
- Alcohol Use Disorder
- Keywords
- Naltrexone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Milky KohnoUniversity, hospital or other
- Collaborators
- Portland VA Medical Center
- Study start
- 2 May 2024 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 23 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alcohol Use Disorder (AUD) | Experimental | Drug: NaltrexoneDrug: 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. |
| Healthy Controls | No intervention | –Baseline measures will be taken but controls will not continue to the drug trial. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 18-60 years old
- Veteran enrolled in VHA healthcare
- must meet diagnosis for recent alcohol-use disorder (DSM-V)
- willing to return for follow-up visits and can participate for 12-weeks
- must not meet DSM-V criteria for a use disorder other than nicotine
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NaltrexoneAlso: Revia12-week randomized double blinded placebo-controlled drug trial titrating drug/placebo dose after 1 week. | Drug | Alcohol Use Disorder (AUD) |
Primary outcome
Change from baseline in alcohol use (number of drinking days, amount used per day)
Time frame: Baseline and Week 12
Drinking days and average number of weekly standard drinks will be measured at baseline and at follow-up
Changes from baseline in peripheral immune biomarkers associated with inflammation
Time frame: Baseline and Week 12
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.
Changes in limbic functional connectivity
Time frame: Baseline and Week 12
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.
Changes from baseline in BOLD signal brain activation during an emotion regulation fMRI task
Time frame: Baseline and Week 12
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.
Changes from baseline in emotion regulation assessed with the Difficulty in Emotion Regulation Scale (DERS)
Time frame: Baseline and Week 12
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.
Changes from baseline in emotion regulation assessed with the Cognitive Emotion Regulation Questionnaire (CERQ)
Time frame: Baseline and Week 12
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.
3 secondary outcomes
Change from baseline in craving (include craving measures/questionnaires)
Time frame: Baseline and Week 12
Differences in baseline trauma exposure (composite score)
Time frame: Baseline and Week 12
Change from baseline in neuropsychological testing scores
Time frame: Baseline and Week 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Naltrexone in people with Alcohol Use Disorder, run by Milky Kohno at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jazryn Nagum (503-721-7964, vhaporhoffmanlab@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in alcohol use (number of drinking days, amount used per day) (time frame: Baseline and Week 12). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.