Neuroimmune Dysfunction in Alcohol Use Disorder
Condition: 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
MeSH terms: Inflammation; Pathologic Processes; Alcoholism; Substance-Related Disorders; Alcohol-Related Disorders; Chemically-Induced Disorders; Alcohol Drinking; Cognitive Dysfunction; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Drinking Behavior
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      The research objective of this project is to characterize the role of the neuroimmune system
      in alcohol use disorder (AUD). The proposed study employs a randomized, double-blind, and
      placebo-controlled design to examine how neuroinflammation, as measured via neuroimaging
      [e.g., magnetic resonance imaging (MRI)], relates to alcohol craving, neurocognitive
      impairment (e.g., memory, attention, etc.), and alcohol use in non-treatment seeking
      individuals with AUD. The study will also determine whether minocycline (MINO), an
      FDA-approved antibiotic medication, affects any of the above listed measures. In the proposed
      study, healthy controls (n = 36) and non-treatment seeking individuals with a current
      Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 AUD diagnosis (n = 36) will be
      randomized to receive either 200 mg of minocycline per day or placebo for approximately 28
      days and complete two laboratory sessions. The first laboratory session will be performed
      immediately before commencing the medication regimen (day 0) and the second will be completed
      after taking the medication daily for approximately 28 days. Within each laboratory session,
      participants will complete a cue reactivity paradigm, neurocognitive performance tasks, and a
      magnetic resonance imaging (MRI) session. Additionally, blood samples will be drawn on days
      0, 7, 14, 21, and 28 of treatment to measure circulating levels of proinflammatory molecules
      in order to identify the specific immune signaling pathways underlying neuroinflammation in
      AUD. Clinical labs (e.g., blood chemistry, liver function tests) and adverse events (AEs)
      will also be assessed at these five visits.
    

Intervention name(s): Minocycline; Sugar pill
Intervention type(s): Drug; Drug
Intervention description(s): 200 mg/day; Matched placebo
Other intervention name(s): Placebo
Intervention MeSH terms: Minocycline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Minocycline