Development of Ibudilast for Alcohol Use Disorder
Condition: Alcohol Use Disorders
MeSH terms: Alcoholism; Alcohol Drinking
Study type: Interventional
Phase: Phase 1

Summary: 
      The objective of this proposal is to advance medication development for alcoholism by
      conducting a safety and initial efficacy study of ibudilast, a neuroimmune modulator and
      phosphodiesterase inhibitor, for alcohol use disorders.
    

Detailed description: 
      Alcohol dependence (AD) is a chronic and relapsing condition affecting 10 million Americans.
      To date, only four pharmacotherapies are approved by the FDA for the treatment of alcoholism
      and their efficacy is modest. Therefore, medication development for AD represents a high
      priority area. Ibudilast (IBUD) is a glial cell modulator that inhibits phosphodiesterases
      (PDE) -4 and -10 and macrophage migration inhibitory factor (MIF). Preclinical data suggest
      that neuroimmune modulation is critical to the rewarding properties of drugs of abuse,
      including alcohol. Further, IBUD has been shown to enhance GDNF release in vivo and GDNF
      modulation has been implicated in alcohol reinstatement in animals, while PDE inhibition has
      been shown to reduce alcohol intake in mice. Together, these findings suggest that
      neuroimmune modulation constitutes a novel target for the treatment of alcoholism. The
      objective of this study is to advance medication development for alcoholism by conducting an
      initial Phase II study of IBUD for AD. Specifically, the proposed study consists of a
      randomized, double-blind, placebo-controlled within-subject crossover design to determine the
      safety, tolerability, and initial human laboratory efficacy of IBUD in a sample of 24
      non-treatment seeking individuals with either alcohol abuse or dependence treated with IBUD
      (50mg BID) and placebo. Participants will complete two separate 7-day inpatient stays at the
      UCLA CTRC during which they will take the study medication, complete an IV alcohol challenge,
      and take part in a stress-exposure and cue-exposure paradigms. Specific aims are to test
      whether IBUD (a) is safe in the context of alcohol administration, (b) attenuates
      alcohol-induced reinforcement, and (c) dampens stress-induced and cue-induced alcohol
      craving. In sum, this study will efficiently evaluate safety and initial efficacy of IBUD
      thereby screening novel medications for AD and elucidating potential mechanisms by which IBUD
      may be clinically efficacious. Results from this study will inform whether a randomized
      controlled trial of IBUD for alcoholism is warranted.
    

Intervention name(s): Ibudilast; Matched placebo
Intervention type(s): Drug; Other
Intervention description(s): Ibudilast is a glial cell modulator that inhibits phosphodiesterases -4 and -10 and macrophage migration inhibitory factor.; A matched placebo (suggar pill) will be administered as a control condition.
Other intervention name(s): MN-166, AV411; Suggar pill
Intervention MeSH terms: Ibudilast
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ibudilast, alcoholism