Improving Treatment Outcomes for Prescription Opioid Dependence

NCT02543944 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 203970R01DA039088
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

Brief Summary

Overall, this proposal seeks to improve treatment strategies for the significant public health problem of prescription opioid dependence by determining whether gabapentin, a non-narcotic pharmaceutical agent with minimal abuse potential and preliminary efficacy, will be effective in ameliorating withdrawal symptoms, craving and illicit drug use in prescription opioid dependent participants undergoing a 10-day detoxification from buprenorphine. In addition, the acceptability and feasibility of transitioning to depot naltrexone therapy will also be determined. If successful, this study would provide data to support further development of gabapentin as a pharmacological tool for improved outcomes during opioid detoxification as well as an integrated outpatient approach for treating prescription opioid dependence.

Conditions

Drug Dependence

Outcome Measures

Primary Outcomes (1)

• Detoxification Phase: Changes in Percent of Illicit Opioid-positive Urine Samples Over Time

  Thrice weekly urine samples obtained during weeks 1-3; data include assessments from week 1 day 1 through week 4 day 1 (up to 10 total samples per participant)

  Week 1 day 1 (study entry) through Week 4 day 1 (first day of NTX transition)

Secondary Outcomes (3)

• NTX Transition Initiation

  3 days (wk 4 day 1 - week 4 day 3)

• Vivitrol Injection Receivers

  5 days (week 4 day 1 to week 4 day 5)

• Detox Phase Completers

  3 weeks (week 1-3)

Study Arms (2)

Gabapentin

ACTIVE COMPARATOR

Gabapentin started on day 3 of week 1, increased up to a maximum dose of 800 mg BID by day 3 of week 2 and maintained for 2 weeks followed by 5-day taper. Buprenorphine (BUP) stabilization up to 12 mg (day 2 of week 1) then a 10-day BUP taper by the end of week 3. During week 4, detoxed subjects get 0.1 mg of clonidine followed by oral naltrexone (NTX) at 6.25 mg and another 6.25 mg (day 1), 25 mg (day 2) and 50 mg (day 3) then depot NTX injection (later on day 3 or day 4).

Drug: Gabapentin; Drug: Buprenorphine; Drug: Clonidine; Drug: Naltrexone (oral); Drug: Naltrexone (depot)

Placebo

PLACEBO COMPARATOR

Participants in this arm begin receiving placebo (microcrystalline cellulose) in twice daily capsules on day 3 of week 1 and continue to do so through the beginning of week 5. Buprenorphine (BUP) stabilization up to 12 mg (day 2 of week 1) then a 10-day BUP taper by the end of week 3. During week 4, detoxed subjects get 0.1 mg of clonidine followed by oral naltrexone (NTX) at 6.25 mg and another 6.25 mg (day 1), 25 mg (day 2) and 50 mg (day 3) then depot NTX injection (later on day 3 or day 4).

Drug: Buprenorphine; Drug: Clonidine; Drug: Naltrexone (oral); Drug: Naltrexone (depot); Drug: Placebo

Interventions

Gabapentin DRUG

N-type calcium channel blocker being examined for its potential efficacy to alleviate opioid withdrawal during buprenorphine-assisted detoxification and transition to depot naltrexone.

Gabapentin

Buprenorphine DRUG

All participants are stabilized on buprenorphine and then undergo a 10 day taper off buprenorphine.

Gabapentin; Placebo

Clonidine DRUG

All participants who successfully taper off buprenorphine receive Clonidine (0.1 mg) prior to induction onto oral naltrexone.

Gabapentin; Placebo

Naltrexone (oral) DRUG

All participants receive increasing doses of oral naltrexone over a 3 day period (day 1: 6.25 and 6.25 mg; day 2: 25 mg; day 3: 50 mg)

Gabapentin; Placebo

Naltrexone (depot) DRUG

All participants who tolerate oral naltrexone at 50 mg will receive the naltrexone injection on either the same day as the 50 mg dose or the day after.

Gabapentin; Placebo

Placebo DRUG

Microcrystalline cellulose

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• be between the ages of 18-65
• be available to attend clinic 6 days a week for approximately 30-60 minutes per day during the first 4 3 weeks
• fulfill Diagnostic Statistical Manual-5 criteria for moderate to severe opioid dependence. These criteria will be ascertained in the following manner: the physician will determine whether the individual is appropriate based on several clinical assessments that are routinely employed by methadone program physicians, including history and severity of opioid use, presence of track marks, prior treatment history, self-reported and/or observed signs and symptoms of opioid withdrawal. If any individual's degree of opioid dependence is questionable, that person will be excluded from further consideration as a participant.
• submit a urine sample negative for benzodiazepines or barbiturates prior to starting the study.

You may not qualify if:

• report having had a severe adverse reaction to study medications
• have an unstable medical condition or stable medical condition that would interact with study medications or participation, including a current chronic pain or other medical condition that requires ongoing opioid agonist treatment (determined by physician assessment)
• have a major psychiatric disorder (psychosis, schizophrenia, bipolar)
• have major depression or anxiety disorder requiring psychoactive medication (as determined by physician)
• physiological dependence on alcohol or drugs other than opioids, tobacco or marijuana (as determined by physician assessment)
• are pregnant, plan to become pregnant or have inadequate birth control, if relevant
• report ongoing use of over-the-counter or prescription drug (including Maalox) that would have major interaction with study drugs
• have any of the following: liver function tests \>3 times normal, blood urea nitrogen and Creatinine outside normal range; electrocardiogram abnormalities including but not limited to: bradycardia (\<50 bpm); prolonged QT interval corrected for heart rate (\>450 msec); Wolff-Parkinson White syndrome; wide complex tachycardia; 2nd degree, Mobitz type II heart block; 3rd degree heart block; left or right bundle branch block; pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic).
• Individuals with anxiety or depression will not be excluded unless they are taking prescription medication for their disorder under a physician's care or findings during screening indicate a need for immediate treatment determined by the study physician and/or the Columbia-Suicide Severity Rating Scale.

Sponsors & Collaborators

• University of Arkansas: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (1)

• Ray A, Mancino MJ, Thostenson JD, Guise JB, Hendrickson HP, Nunes EV, Oliveto AH. Randomized, placebo-controlled trial of gabapentin during outpatient buprenorphine-assisted taper and transition to injectable naltrexone. Am J Drug Alcohol Abuse. 2025;51(6):761-775. doi: 10.1080/00952990.2025.2564757. Epub 2025 Dec 16.

  PMID: 41401348 DERIVED

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Gabapentin; Buprenorphine; Clonidine; Naltrexone

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Naloxone

Results Point of Contact

• Title: Dr. Alison H. Oliveto, PhD
• Organization: University of Arkansas for Medical Sciences

olivetoalison@uams.edu

501-526-8441

Study Officials

• Alison Oliveto, PhD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

• Michael Mancino, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: September 7, 2015
• Study Start: February 1, 2016
• Primary Completion: May 25, 2021
• Study Completion: May 31, 2021
• Last Updated: July 28, 2022
• Results First Posted: July 28, 2022

Record last verified: 2022-05

Locations

US (1)