Neuroimmune Dysfunction in Alcohol Use Disorder

NCT04210713 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: HP-000808915K01AA026005-03
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this proposal is to advance medication development for alcohol use disorder by examining the efficacy and mechanisms of action of minocycline, a neuroimmune modulator, as a potential treatment. This study has important clinical implications, as the available treatments for alcohol use disorder are only modestly effective and testing novel medications is a high research priority.

Conditions

Alcohol Drinking; Alcohol-Related Disorders; Disease; Inflammation; Alcoholism; Cognitive Dysfunction; Pathologic Processes; Drinking Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorder; Cognition Disorder; Neurocognitive Disorders; Minocycline; Anti-Bacterial Agents; Anti-Infective Agents

Keywords

Minocycline

Outcome Measures

Primary Outcomes (13)

• Neuroinflammation

  A multimodal MRI approach consisting of Diffusion Tensor Imaging (DTI) with free water imaging and Magnetic Resonance Spectroscopy (MRS) will be utilized to assess neuroinflammation

  Change from baseline after 28 days of medication dosing

• Cue-Induced Alcohol Craving

  Participants will listen to a 5-minute guided cue exposure script, during which they are exposed to both a neutral and their preferred alcoholic beverage. Prior to beginning the paradigm and after each cue exposure participants will rate their alcohol craving using the "Alcohol Urge Questionnaire (AUQ)" and cigarette craving using the "Brief Questionnaire on Smoking Urges (BQSU)." Both scales range from 1 to 7 with higher scores reflecting more craving.

  Change from baseline after 28 days of medication dosing

• Alcohol consumption

  Total drinks consumed assessed using the Timeline Follow Back

  Change from baseline after 28 days of medication dosing

• Verbal Fluency/Language

  Wechsler Abbreviated Scale of Intelligence (WASI)-Vocabulary, WASI-Similarities, Verbal Fluency (Animals), with higher scores indicating greater intellectual ability.

  Change from baseline after 28 days of medication dosing

• Speed of processing

  Brief Assessment of Cognition in Schizophrenia (BACS)-Symbol Coding \[scored by number of correct numerals (range: 0 -110)\]

  Change from baseline after 28 days of medication dosing

• Speed of processing

  Trail Making Test: Part A (scored by time to complete test with lower scores being better)

  Change from baseline after 28 days of medication dosing

• Speed of processing

  Grooved Pegboard (scored as a sum of the total time, total number of drops, and the total number of pegs correctly placed in the board with higher scores corresponding to worse performance)

  Change from baseline after 28 days of medication dosing

• Working Memory

  Wechsler Memory Scale (WMS)-Spatial Span (scored up to 32 correct series), Letter-Number Span (scored up to 30 correct series)

  Change from baseline after 28 days of medication dosing

• Attention

  Continuous Performance Test

  Change from baseline after 28 days of medication dosing

• Problem Solving/Executive Functioning

  Wisconsin Card Sorting Test-64

  Change from baseline after 28 days of medication dosing

• Inhibition/Impulsivity

  Stop-Signal Reaction Time

  Change from baseline after 28 days of medication dosing

• Verbal Learning

  Hopkins Verbal Learning Test

  Change from baseline after 28 days of medication dosing

• Visual Learning

  Brief Visuospatial Memory Test \[scoring is as follows, 1) Total recall: The sum of all valid items generated across learning trials 1-3, 2) Delayed recall: The number of valid items generated after a delay (trial 4), 3) Percent retained: Delayed recall score divided by the higher of trial 2 or 3 × 100, and 4) Recognition Discrimination Index: True positive responses minus false positive responses.\]

  Change from baseline after 28 days of medication dosing

Secondary Outcomes (3)

• Peripheral Proinflammatory Marker levels

  At baseline (day zero) and after 7, 14, and 21 and 28 days of medication dosing

• Alcohol Use Disorder Severity

  At baseline (day zero) and after 28 days of medication dosing

• Gut microbiota

  At baseline (day zero) and after 7, 14, and 21 and 28 days of medication dosing

Study Arms (4)

AUD-Minocycline

ACTIVE COMPARATOR

Participants diagnosed with alcohol use disorder will be randomly assigned to take minocycline for 4 weeks. The randomization is double-blinded and will alternate between minocycline and placebo.

Drug: Minocycline

AUD-Placebo

PLACEBO COMPARATOR

Participants diagnosed with alcohol use disorder will be randomly assigned to take placebo for 4 weeks. The randomization is double-blinded and will alternate between minocycline and placebo.

Drug: Sugar pill

Healthy Control-Minocycline

ACTIVE COMPARATOR

Healthy control participants will be randomly assigned to take minocycline for 4 weeks. The randomization is double-blinded and will alternate between minocycline and placebo.

Drug: Minocycline

Healthy Control-Placebo

PLACEBO COMPARATOR

Healthy control participants will be randomly assigned to take placebo for 4 weeks. The randomization is double-blinded and will alternate between minocycline and placebo.

Drug: Sugar pill

Interventions

Minocycline DRUG

200 mg/day

AUD-Minocycline; Healthy Control-Minocycline

Sugar pill DRUG

Matched placebo

Also known as: Placebo

AUD-Placebo; Healthy Control-Placebo

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet DSM-5 diagnostic criteria for an AUD
• In the 30-day period before enrollment, consume ≥ 14 and ≥ 7 standard drinks per week for men and women, respectively, AND
• In the 30-day period before enrollment, engage in heavy drinking (5 or more drinks for men, 4 or more drinks for women) and ≥ 5 times per month

You may not qualify if:

• Currently in treatment for AUD, a history of treatment within the 30 days before enrollment, or currently seeking immediate treatment
• Current (last 12 months) DSM-5 diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine
• Currently prescribed a psychotropic medication for the treatment of schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, depressive disorders, anxiety disorders, and mood disorders.
• Lifetime DSM-5 diagnosis of schizophrenia spectrum and other psychotic disorders and bipolar and related disorders
• Positive urine toxicology screen for the following substances: cocaine, opiates, amphetamines, methamphetamine, phencyclidine, barbiturates, benzodiazepine, methadone, and tricyclic antidepressants.
• Self-reported daily use of cannabidiol (CBD) or opioids (including prescribed)
• Serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised
• If female: pregnancy, nursing, or refusal to use reliable method of birth control; if using hormonal contraceptives, refusal to use secondary birth control method
• Any autoimmune or inflammatory medical disorder or medical condition that may interfere with safe study participation and/or study aims (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes)
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or γ-glutamyl transferase (GGT) ≥ 4 times upper normal limit
• Attempted suicide in the past 3 years and/or serious suicidal intention or plan within the past year
• Currently on prescription medication that contraindicates use of minocycline, including but not necessarily limited to: isoretinoin, ergot alkaloids, and anti-coagulants.
• Previously known hypersensitivity to tetracyclines
• Current or recent (within one month) treatment with any antibiotic
• Regular use of a prebiotic or probiotic supplement

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Maryland Psychiatric Research Center (MPRC) Treatment Research Program (TRP)

Catonsville, Maryland, 21228, United States

Location

Related Publications (1)

• Wheeler PB, Mackey CD, Moskal D, Brady DJ, Foster KT, Marks RM, Dickerson DL, Kelly DL, Bennett ME, Roche DJO. Religiosity and the relationship between sexual trauma, alcohol use, and sleep quality: a moderated mediation model. Alcohol Alcohol. 2025 May 14;60(4):agaf030. doi: 10.1093/alcalc/agaf030.

  PMID: 40483726 DERIVED

MeSH Terms

Conditions

Alcohol Drinking; Alcohol-Related Disorders; Disease; Inflammation; Alcoholism; Cognitive Dysfunction; Pathologic Processes; Drinking Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders; cyclopia sequence

Interventions

Minocycline; Sugars

Condition Hierarchy (Ancestors)

Behavior; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Carbohydrates

Study Officials

• Daniel Roche, PhD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 26, 2019
• Study Start: February 3, 2020
• Primary Completion: September 20, 2023
• Study Completion: September 20, 2023
• Last Updated: December 1, 2023

Record last verified: 2023-11

Locations

US (1)