Clinical trial NCT03205423: Medication Development for Opioid and Alcohol Abuse
Official title: Medication Development for Opioid and Alcohol Abuse: Laboratory Study in Humans.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid-use Disorder
Alcohol Use Disorder
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
First posted: 2017-07-02
Enrollment: 17
Sex: ALL
Minimum age (years): 21
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will be randomized to receive one of two treatment conditions: gabapentin 0 mg or gabapentin 1800 mg/day first. Participants crossover to the 2nd gabapentin condition following a washout period.
Primary purpose: BASIC_SCIENCE

Brief summary: The present proposal will evaluate the ability of gabapentin maintenance to reduce the abuse liability of alcohol, oxycodone, and alcohol in combination with oxycodone in participants with both Opioid Use Disorder and Alcohol Use Disorder.

Detailed description: Currently, the abuse of prescription opioid medications is a pervasive problem in the U.S. In addition, co-abuse of opioids and alcohol represents a significant problem from the perspective of increased toxicity and decreased success in treatment. Surprisingly few studies have examined the effects of combined administration of opioids and alcohol in humans, and no clinical studies have examined the reinforcing effects of this combination. The current 8-9-week inpatient study will systematically evaluate gabapentin because it shows promise for treating both opioid and alcohol use disorders (OUD and AUD). The guiding principle is that a medication's effects on positive subjective responses and reinforcing effects are the best laboratory procedures to date in predicting its clinical efficacy. We will examine the ability of gabapentin (0 mg or 1800 mg) to alter opioid-, alcohol-,and combined opioid/alcohol-mediated responses. Participants will meet DSM-5 criteria for moderate-severe OUD and be physically dependent on opioids. In addition, participants will meet DSM-5 criteria for moderate-severe AUD, but they will not be physically dependent on alcohol. All of the participants will be maintained on oral morphine throughout the study and different doses of gabapentin will be evaluated.

Eligibility criteria: Inclusion Criteria:

1. DSM-5 criteria for moderate-severe opioid use disorder with physical dependence.
2. DSM-5 criteria for moderate-severe alcohol use disorder without physical dependence.
3. No current major mood, psychotic, or anxiety disorder.
4. Physically healthy.
5. Able to perform study procedures.
6. 21-59 years of age.
7. Normal body weight/Within 20% of body weight (for appropriate frame) according to 1983 Metropolitan Weight tables.
8. Current or history of illicit opioid use.
9. Current use of opioids in amounts and/or frequencies that meet or exceed those used in the proposed study (e.g., 3-4 tablets of a Rx opioid medication per day or 1-2 bags of heroin per day). Not seeking treatment for opioid use disorder (neutral attitude or not wanting treatment only).
10. Participants will consume alcohol at least 3 times per week (15 drinks per week for men and 8 drinks per week for women). In addition, they will drink alcohol and use opioids simultaneously.

Exclusion Criteria:

1. DSM-5 criteria for substance use disorder (moderate to severe) on drugs other than opioids, alcohol, nicotine or caffeine (must be less than 500 mg caffeine daily).
2. Participants requesting treatment.
3. Pregnancy or lactation.
4. Current or recent history of significant violent or suicidal behavior and/or suicidal/homicidal risk.
5. Cannot read or understand the self-report assessment forms unaided, or are so severely disabled that they cannot comply with the requirements of the study.
6. Elevated liver function tests (i.e., AST and ALT \> 3 times the upper limit of normal) or impaired renal function (creatinine must be within normal limits).
7. Physical disorders that might make participation hazardous such as AIDS, cancer, hypertension (blood pressure \> 140/90), uncontrolled diabetes, pulmonary hypertension or heart disease (please note that participants will be asked about previous visits to a cardiologist, chest pain, or strong palpitations; if these exist, they will be referred to a cardiologist and excluded unless cleared for participation by a cardiologist).
8. Current major Axis I psychopathology, other than OUD and AUD (e.g., mood disorder with functional impairment, schizophrenia), that might interfere with ability to participate in the study.
9. Sensitivity, allergy, or contraindication to opioids, alcohol, gabapentin or similar medications.
10. Taken an investigational drug within the past 30 days.
11. Current or history of chronic pain within the past 3 months.
12. Taking prescription psychotropic medications that would potentially interfere with study procedures.

Primary outcomes:
measure: Peak Positive Subjective Responses to Placebo.
timeFrame: Assessed every 15 minutes following drug administration,for a total of 360 minutes. "Peak" drug effect is the highest rating throughout the entire testing session.
measure: Peak Positive Subjective Responses to Oxycodone (30mg) + Low Alcohol Dose.
timeFrame: Assessed every 15 minutes following drug administration, for a total of 360 minutes. "Peak" drug effect is the highest rating throughout the entire testing session.
measure: Peak Positive Subjective Responses to Oxycodone (30mg) + High Alcohol Dose.
timeFrame: Assessed every 15 minutes following drug administration, for a total of 360 minutes. "Peak" drug effect is the highest rating throughout the entire testing session.
measure: Peak Positive Subjective Responses to Oxycodone (15mg) + High Alcohol Dose.
timeFrame: Assessed every 15 minutes following drug administration, for a total of 360 minutes. "Peak" drug effect is the highest rating throughout the entire testing session.
measure: Peak Positive Subjective Responses to Oxycodone (15mg) + Low Alcohol Dose.
timeFrame: Assessed every 15 minutes following drug administration, for a total of 360 minutes. "Peak" drug effect is the highest rating throughout the entire testing session.
measure: Peak Positive Subjective Responses to Low Alcohol Dose.
timeFrame: Assessed every 15 minutes following drug administration, for a total of 360 minutes. "Peak" drug effect is the highest rating throughout the entire testing session.
measure: Peak Positive Subjective Responses to High Alcohol Dose.
timeFrame: Assessed every 15 minutes following drug administration, for a total of 360 minutes. "Peak" drug effect is the highest rating throughout the entire testing session.
measure: Peak Positive Subjective Responses to Oxycodone (30mg)
timeFrame: Assessed every 15 minutes following drug administration, for a total of 360 minutes. "Peak" drug effect is the highest rating throughout the entire testing session.
measure: Peak Positive Subjective Responses to Oxycodone (15mg)
timeFrame: Assessed every 15 minutes following drug administration, for a total of 360 minutes. "Peak" drug effect is the highest rating throughout the entire testing session.
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute in the Division on Substance Use Disorders
state: New York
Study officials:
affiliation: New York State Psychiatric Institute / Columbia University Medical Center
name: Sandra D. Comer, PhD.
role: PRINCIPAL_INVESTIGATOR
References: