Modafinil for the Treatment of Alcohol Use Disorders
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism; Alcohol Drinking
Intervention: Modafinil; Placebo
Intervention description: Modafinil 300 mg by mouth daily; Placebo
Intervention MeSH terms: Modafinil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      Alcohol use disorder (AUD) is a major cause of morbidity and mortality and more treatments
      are needed, especially pharmacotherapies. There are a variety of efficacious treatments for
      AUD, but effect sizes are small, and vary from study to study. Medications may be more
      effective if particular subgroups of AUD are targeted. Identifying the mechanisms of action
      of a particular medication will help identify the subtypes more likely to respond to therapy.
      Global impulse control is a rational treatment target, and improving it is a likely
      mechanisms by which some medications for AUD work, especially in subtypes of AUD with
      impaired impulse control at baseline. Modafinil is a medication that is FDA approved for the
      treatment of narcolepsy, and is relatively safe and tolerable. There is reason to believe it
      may improve impulse control, and underlying neural circuitry, and may work best to improve
      alcohol use outcomes in AUD with poor impulse control. The overall aim of this study is to
      investigate the effects of modafinil on task performance and the integrity of neural circuits
      mediating response inhibition in treatment-seeking AUD with poor response inhibition, to
      establish target engagement. Secondary aims are to measure whether target engagement mediates
      improvement in alcohol use outcomes, and to utilize machine learning to identify neural and
      behavioral markers which best predict treatment outcomes. Twenty-four individuals with AUD
      and impaired response inhibition will be enrolled in the study, randomized to modafinil or
      placebo, and treated for 6 weeks. Functional magnetic resonance imaging brain scans during a
      response inhibition task and during rest will be obtained at baseline and 2 weeks. Aversive
      stimuli will be included in the response inhibition task to assure that efficacy generalizes
      to several conditions. Diffusion imaging and arterial spin labeling sequences will also be
      obtained. Investigators predict that modafinil will significantly increase brain activity in
      the medial and lateral prefrontal cortex during response inhibition, thereby establishing
      target engagement, and that it will improve alcohol use outcomes. Findings will provide
      information about whether or not a larger R01 trial investigating the efficacy of modafinil
      for individuals with AUD and impaired response inhibition is warranted.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and females age 18-65 meeting Diagnostic and Statistical Manual V criteria for
             moderate or severe AUD in the past year

          -  Interested in cutting down or quitting

          -  Able to provide voluntary informed consent

          -  Have at least 4 heavy drinking days (≥ 5 drinks per day for men, and 4 for women) in
             the past 60 days

          -  Stop signal reaction time on a stop signal task>233

        Exclusion Criteria:

          -  Severe neurological conditions (severe traumatic brain injury/stroke/active seizure
             disorder)

          -  Heart disease [mitral valve prolapse, left ventricular hypertrophy, cardiac
             arrhythmias, angina, myocardial infarction, unstable angina, cardiac syncope or
             pre-syncope, any electrocardiogram (ECG) finding that suggests the presence of one of
             these conditions]

          -  Uncontrolled hypertension (systolic blood pressure >160, diastolic blood pressure
             >100)

          -  Heart rate greater than 70% of the maximum expected for age [0.70(220-age)]

          -  Chronic renal or hepatic failure

          -  Recent pancreatitis

          -  Insulin-dependent diabetes

          -  Other urgent medical problems

          -  Elevated liver function tests (AST or ALT greater than 4 times normal; modafinil is
             metabolized primarily by the liver)

          -  Schizophrenia, schizoaffective disorder, Bipolar I disorder, suicidal thoughts in the
             last month

          -  Current moderate or severe other substance use disorder (SUD) (except nicotine or
             marijuana)

          -  Active legal problems with the potential to result in incarceration

          -  Pregnancy or lactation, or child bearing age and not on birth control

          -  Current daily use of anti-craving medications, stimulants, benzodiazepines, opiates,
             anti-psychotics; current daily use of tricyclic antidepressants, bupropion, monoamine
             oxidase inhibitors, serotonin and norepinephrine reuptake inhibitors, or therapeutic
             doses (for bipolar disorder) of mood stabilizers

          -  Taking a medication contraindicated for use with modafinil