Medication Development for Opioid and Alcohol Abuse

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03205423

Enrollment

Registered

2017-07-02

Start date

2017-08-01

Completion date

2021-12-30

Last updated

2024-09-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alcohol Use Disorder, Opioid-use Disorder

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.

Interventions

DRUGGabapentin

Maintenance medication under investigation for its ability to alter the subjective and reinforcing effects of experimenter-administered doses of oxycodone and alcohol.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Outcomes Assessor)

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.

Eligibility

Sex/Gender

ALL

Age

21 Years to 59 Years

Healthy volunteers

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.

Design outcomes

Primary

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Gabapentin (Within-Subjects) Participants are randomized to receive gabapentin once daily at 8am.	17
Total	17

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Personal	1	1
Overall Study	Physician Decision	0	2

Baseline characteristics

Characteristic	Gabapentin (Within-Subjects)
Age, Continuous	46.7 years STANDARD_DEVIATION 12.6
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	10 Participants
Race (NIH/OMB) More than one race	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	5 Participants
Region of Enrollment United States	17 Participants
Sex: Female, Male Female	15 Participants
Sex: Female, Male Male	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 17	0 / 17
other Total, other adverse events	1 / 17	1 / 17
serious Total, serious adverse events	0 / 17	0 / 17