Pharmacological Treatment of Comorbid Alcohol and Marijuana Withdrawal and Dependence

Study Overview
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Brief Summary
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The primary aim of the supplemental study is to provide POC testing of aprepitant as a treatment for comorbid alcohol and cannabis dependence. The data analysis plan specified in the parent grant will likewise be applied to the supplemental project to test for effects of aprepitant vs placebo on measures of alcohol and cannabis use and protracted withdrawal. The primary hypothesis is that subjects treated with aprepitant will have significantly less alcohol and marijuana use than subjects treated with placebo.

Detailed Description
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Consistent with the scope and methods of the parent grant, this was a randomized, double-blind, placebo-controlled, parallel groups, Phase II, single-site, 8-week clinical trial of aprepitant 125 mg/d or placebo. Participants were 20 outpatients seeking treatment for concurrent alcohol and cannabis dependence. All participants received weekly protocol-specific counseling. Research assessments occurred weekly through the treatment phase of the 8-week study. Post treatment follow-up assessments occurred at Weeks 9 and 12.

Official Title
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Pharmacological Treatment of Comorbid Alcohol and Marijuana Withdrawal and Dependence

Conditions
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Cannabis Dependence, Alcohol Dependence, Cannabis Use Disorder, Alcohol Use Disorder

Intervention / Treatment
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* Drug: aprepitant
* Drug: Placebo
* Behavioral: Manual-guided behavioral counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females from 18-70 years of age Meets DSM IV criteria for current alcohol and cannabis dependence Seeking research-based outpatient treatment for alcohol and cannabis dependence that involves daily oral medication Negative BAC and a CIWA score < 9 at randomization Exclusion Criteria: Significant medical disorders or use of medications that will increase potential risk or influence study outcomes Females who are pregnant, nursing or who are sexually active with child-bearing potential and refuse to use an effective, non hormonal method of birth control during the study and for up to 4 weeks after study termination• Treatment with an investigational drug during the previous month Prior treatment with NK1 antagonists Participants for whom treatment is being mandated by a legal authority• Inability to understand and/or comply with the provisions of the protocol and consent form

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental: aprepitant 125 mg/day<br>125 mg aprepitant daily for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling. | Drug: aprepitant<br>* 125 mg daily for 8 weeks.<br>* Other names: Emend;Behavioral: Manual-guided behavioral counseling<br>* Standardized manual-guided behavioral counseling performed 1 time per week for 8 weeks in conjunction with study drug or placebo.<br>* Other names: Manual-guided therapy;|
| Placebo Comparator: Placebo 125mg/d<br>Matched placebo pill given daily for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling. | Drug: Placebo<br>* Placebo daily for 8 weeks.<br>Behavioral: Manual-guided behavioral counseling<br>* Standardized manual-guided behavioral counseling performed 1 time per week for 8 weeks in conjunction with study drug or placebo.<br>* Other names: Manual-guided therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Week 0 in Cannabis Use Using Urinary CN-THCCOOH Levels at Week 8 | Urinary THC/Cr ratio, also known as CN-THCCOOH (creatinine normalized tetrahydrocannabinol carboxylic acid), is a highly sensitive and specific quantitative analytic procedure to determine current marijuana metabolite levels in the urine as well as new marijuana use or abstinence. Gas chromatography mass spectrometric levels of 11-nor-9-carboxy-9-THC (THC-COOH), the primary marijuana metabolite, are normalized to the urine creatinine (CN) concentration to reduce the variability of drug measurement attributable to urine dilution. Negative values indicate decreased use. Change = (Week 8 value - Week 0 value). | Week 0 and Week 8 | 
| Change From Week 0 in Drinking Quantity and Frequency Using Drinks Per Week at Week 8 | Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. Change = (Week 8 - Week 0). More negative values indicate less use of alcohol. | Week 0 and Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Emend, NK1 receptor antagonist, Cannabis Treatment, Alcohol Treatment, Alcohol-Related Disorders, Cannabis-Related Disorders, Substance-Related Disorders, Alcohol, Cannabis, aprepitant