Modafinil for the Treatment of Alcohol Use Disorders

• Sponsor: The Mind Research Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT03424681
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Actual Duration (Months): 8.6
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Modafinil; Other: Placebo	Phase 2

Detailed Description

see above.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Modafinil for the Treatment of Alcohol Use Disorders: Targeting Impaired Response Inhibition
• Actual Study Start Date: Dec 11, 2017
• Actual Primary Completion Date: Aug 31, 2018
• Actual Study Completion Date: Aug 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Modafinil Modafinil 300 mg by mouth each day	Drug: Modafinil; Modafinil 300 mg by mouth daily; Other Names: Provigil
Placebo Comparator: Placebo Identical looking capsule/number of capsules by mouth each day without active medication	Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Time to Relapse [over 9 weeks]

   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

Secondary Outcome Measures

1. Drinks Per Drinking Day [Weeks 4-6]

   drinks per drinking day weeks 4-6

2. Drinks Per Week [Weeks 4-6]

   drinks per week weeks 4-6

3. Percent Days Abstinent [Weeks 4-6]

   percent days abstinent weeks 4-6

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mind Research Network	Albuquerque	New Mexico	United States	87106

Sponsors and Collaborators

• The Mind Research Network

Investigators

• Principal Investigator: Claire Wilcox, MD, Mind Research Network

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 30, 2018

More Information

Publications

None provided.

• Responsible Party: Claire Wilcox, Associate Professor, The Mind Research Network
• ClinicalTrials.gov Identifier: NCT03424681
• Other Study ID Numbers: FP00002746
• First Posted: Feb 7, 2018
• Last Update Posted: May 26, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Alcoholism; Alcohol Drinking; Modafinil

Study Results

Participant Flow

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 300 mg by mouth each day Modafinil: Modafinil 300 mg by mouth daily	Identical looking capsule/number of capsules by mouth each day without active medication Placebo: Placebo
Period Title: Overall Study
STARTED	6	6
COMPLETED	6	5
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Modafinil	Placebo	Total
Arm/Group Description	Modafinil 300 mg by mouth each day Modafinil: Modafinil 300 mg by mouth daily	Identical looking capsule/number of capsules by mouth each day without active medication Placebo: Placebo	Total of all reporting groups
Overall Participants	6	6	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	6 100%	12 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34 (12)	31 (15)	33 (13)
Sex: Female, Male (Count of Participants)
Female	1 16.7%	4 66.7%	5 41.7%
Male	5 83.3%	2 33.3%	7 58.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 16.7%	0 0%	1 8.3%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 83.3%	6 100%	11 91.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	6 100%	6 100%	12 100%

Outcome Measures

1. Primary Outcome

Title	Time to Relapse
Description	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
Time Frame	over 9 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 300 mg by mouth each day Modafinil: Modafinil 300 mg by mouth daily	Identical looking capsule/number of capsules by mouth each day without active medication Placebo: Placebo
Measure Participants	6	6
Mean (Standard Deviation) [days]	16 (27)	43 (32)

2. Secondary Outcome

Title	Drinks Per Drinking Day
Description	drinks per drinking day weeks 4-6
Time Frame	Weeks 4-6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 300 mg by mouth each day Modafinil: Modafinil 300 mg by mouth daily	Identical looking capsule/number of capsules by mouth each day without active medication Placebo: Placebo
Measure Participants	5	6
Mean (Standard Deviation) [drinks/drinking day]	5 (6)	2 (2)

3. Secondary Outcome

Title	Drinks Per Week
Description	drinks per week weeks 4-6
Time Frame	Weeks 4-6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 300 mg by mouth each day Modafinil: Modafinil 300 mg by mouth daily	Identical looking capsule/number of capsules by mouth each day without active medication Placebo: Placebo
Measure Participants	5	6
Mean (Standard Deviation) [drinks/week]	12 (13)	3 (5)

4. Secondary Outcome

Title	Percent Days Abstinent
Description	percent days abstinent weeks 4-6
Time Frame	Weeks 4-6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 300 mg by mouth each day Modafinil: Modafinil 300 mg by mouth daily	Identical looking capsule/number of capsules by mouth each day without active medication Placebo: Placebo
Measure Participants	5	6
Mean (Standard Deviation) [percentage of days]	77 (22)	86 (21)

Adverse Events

Time Frame	10 weeks
Arm/Group Title	Modafinil		Placebo
Arm/Group Description	Modafinil 300 mg by mouth each day Modafinil: Modafinil 300 mg by mouth daily		Identical looking capsule/number of capsules by mouth each day without active medication Placebo: Placebo
All Cause Mortality
	Modafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Modafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Modafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/6 (0%)
Skin and subcutaneous tissue disorders
rash requiring steroids	1/6 (16.7%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.