Alcohol Dependence, Alcohol Use Disorder, Cannabis Dependence, Cannabis Use Disorder
Conditions
Keywords
Cannabis Treatment, Alcohol Treatment, Alcohol-Related Disorders, Cannabis-Related Disorders, Substance-Related Disorders, Emend, NK1 receptor antagonist, Alcohol, Cannabis, aprepitant
Brief summary
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
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.
Interventions
DRUGaprepitant
125 mg daily for 8 weeks.
DRUGPlacebo
Placebo daily for 8 weeks.
BEHAVIORALManual-guided behavioral counseling
Standardized manual-guided behavioral counseling performed 1 time per week for 8 weeks in conjunction with study drug or placebo.
Sponsors
National Institute on Drug Abuse (NIDA)
The Scripps Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Week 0 in Cannabis Use Using Urinary CN-THCCOOH Levels at Week 8 | Week 0 and 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). |
| Change From Week 0 in Drinking Quantity and Frequency Using Drinks Per Week at Week 8 | Week 0 and 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aprepitant: 125mg/Day 125mg/d aprepitant for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling. | 10 |
| Matched Placebo Matched Placebo daily for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Aprepitant: 125mg/Day | Matched Placebo | Total |
|---|---|---|---|
| Age, Continuous | 34.5 years STANDARD_DEVIATION 13.5 | 35.5 years STANDARD_DEVIATION 9.3 | 35.0 years STANDARD_DEVIATION 11.3 |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 10 | 6 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
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).
Time frame: Week 0 and Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant: 125mg/Day | Change From Week 0 in Cannabis Use Using Urinary CN-THCCOOH Levels at Week 8 | 198.3 ng/mg | Standard Deviation 389.4 |
| Matched Placebo | Change From Week 0 in Cannabis Use Using Urinary CN-THCCOOH Levels at Week 8 | 55.9 ng/mg | Standard Deviation 239.3 |
Primary
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.
Time frame: Week 0 and Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant: 125mg/Day | Change From Week 0 in Drinking Quantity and Frequency Using Drinks Per Week at Week 8 | -21.0 drinks/week | Standard Deviation 16.1 |
| Matched Placebo | Change From Week 0 in Drinking Quantity and Frequency Using Drinks Per Week at Week 8 | -10.7 drinks/week | Standard Deviation 17.1 |