Modafinil for the Treatment of Alcohol Use Disorders

NCT03424681 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: FP00002746
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (1)

• Time to Relapse

  Time to relapse, starting 7 days after treatment initiation (after medication has reached maximum tolerated dose), to heavy drinking days (\>4 standard drinks for men, \>3 standard drinks for women); abstinent is coded as 9\*7=63; dropout not included

  over 9 weeks

Secondary Outcomes (3)

• Drinks Per Drinking Day

  Weeks 4-6

• Drinks Per Week

  Weeks 4-6

• Percent Days Abstinent

  Weeks 4-6

Study Arms (2)

Modafinil

EXPERIMENTAL

Modafinil 300 mg by mouth each day

Drug: Modafinil

Placebo

PLACEBO COMPARATOR

Identical looking capsule/number of capsules by mouth each day without active medication

Other: Placebo

Interventions

Modafinil DRUG

Modafinil 300 mg by mouth daily

Also known as: Provigil

Modafinil

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Mind Research Network: lead

Study Sites (1)

Mind Research Network

Albuquerque, New Mexico, 87106, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Modafinil

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Claire Wilcox
• Organization: Mind Research Network

cwilcox@mrn.org

5052725028

Study Officials

• Claire Wilcox, MD

  Mind Research Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: February 7, 2018
• Study Start: December 11, 2017
• Primary Completion: August 31, 2018
• Study Completion: August 31, 2018
• Last Updated: May 26, 2020
• Results First Posted: May 26, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)