Medication Development for Opioid and Alcohol Abuse

Medication Development for Opioid and Alcohol Abuse: Laboratory Study in Humans

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.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder; Opioid-use Disorder
• Intervention / Treatment: Drug: Gabapentin

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute in the Division on Substance Use Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Gabapentin 0 mg; once daily at 8am	Drug: Gabapentin; Maintenance medication under investigation for its ability to alter the subjective and reinforcing effects of experimenter-administered doses of oxycodone and alcohol.
Active Comparator: Gabapentin 1800 mg; once daily at 8am	Drug: Gabapentin; Maintenance medication under investigation for its ability to alter the subjective and reinforcing effects of experimenter-administered doses of oxycodone and alcohol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Positive Subjective Responses to Placebo.	Self-reported "High" measured on a 0-100 self-report visual analog scale. 0= Not-At-All 100=Extremely	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.
Peak Positive Subjective Responses to Oxycodone (30mg) + Low Alcohol Dose.	Self-reported "High" measured on a 0-100 self-report visual analog scale. 0= Not-At-All 100=Extremely	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.
Peak Positive Subjective Responses to Oxycodone (30mg) + High Alcohol Dose.	Self-reported "High" measured on a 0-100 self-report visual analog scale. 0= Not-At-All 100=Extremely	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.
Peak Positive Subjective Responses to Oxycodone (15mg) + High Alcohol Dose.	Self-reported "High" measured on a 0-100 self-report visual analog scale. 0= Not-At-All 100=Extremely	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.
Peak Positive Subjective Responses to Oxycodone (15mg) + Low Alcohol Dose.	Self-reported "High" measured on a 0-100 self-report visual analog scale. 0= Not-At-All 100=Extremely	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.
Peak Positive Subjective Responses to Low Alcohol Dose.	Self-reported "High" measured on a 0-100 self-report visual analog scale. 0= Not-At-All 100=Extremely	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.
Peak Positive Subjective Responses to High Alcohol Dose.	Self-reported "High" measured on a 0-100 self-report visual analog scale. 0= Not-At-All 100=Extremely	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.
Peak Positive Subjective Responses to Oxycodone (30mg)	Self-reported "High" measured on a 0-100 self-report visual analog scale. 0= Not-At-All 100=Extremely	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.
Peak Positive Subjective Responses to Oxycodone (15mg)	Self-reported "High" measured on a 0-100 self-report visual analog scale. 0= Not-At-All 100=Extremely	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.

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Investigators: Principal Investigator: Sandra D. Comer, PhD., New York State Psychiatric Institute / Columbia University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: June 29, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Alcohol-Related Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Alcoholism; Disease; Opioid-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: 7476

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No