Improving Treatment Outcomes for Prescription Opioid Depe... | NCT02543944

NCT02543944

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
R01DA039088	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Institute on Drug Abuse (NIDA)	NIH

Description Module

Detailed Description

Opioid dependence is a serious public health problem, particularly with the dramatic rise in prescription opioid abuse, but long-term opioid agonist maintenance with methadone or buprenorphine (BUP) may not be optimal for many prescription opioid abusers. Yet current opioid detoxification strategies are limited by high relapse rates and/or lack of efficacy in relieving subjective symptoms. In addition, antagonist maintenance with naltrexone (NTX), which may be an optimal longer-term strategy for this population, requires prior opioid detoxification and has been associated with relatively poor outcomes in heroin abusers. This application takes a novel, broad approach to address the problem of prescription opioid dependence by determining the 1) utility of adjunct gabapentin (GBP) during outpatient BUP detoxification to improve initial outcomes and 2) feasibility of transitioning prescription opioid -dependent patients to depot NTX following detoxification, which may improve longer-term outcomes. GBP, an N-type calcium channel blocker with low abuse potential, potentiates opioid analgesia, decreases both postoperative morphine consumption and movement-related pain, and reverses tolerance to the antinociceptive effects of morphine. GBP is also well tolerated and effective in reducing craving and illicit opioid use in pilot detoxification trials. The efficacy and tolerability of adjunct GBP during BUP-assisted detoxification and the feasibility of subsequent transition to depot NTX therapy in prescription opioid -dependent participants will be assessed. This 12-week, randomized, placebo-controlled clinical trial will determine the potential utility of adjunct GBP in 150 prescription opioid -dependent individuals undergoing outpatient BUP detoxification and whether transition to short-term depot NTX therapy is feasible. Our three specific aims are to determine (1) the efficacy and tolerability of GBP to reduce craving and illicit use of opioids in prescription opioid-dependent individuals undergoing outpatient BUP detoxification; (2) acceptability and feasibility of transition to, and short-term maintenance on, depot NTX following detoxification; and (3) prognosticators of completion of the BUP taper, successful induction onto depot NTX, symptomatology, and longer-term outcomes. Currently, the only Food and Drug Administration (FDA)-approved medications for the treatment of opioid withdrawal are the opioid agonists methadone and BUP, both of which have abuse liability, and NTX, which can produce low levels of withdrawal-like symptoms, especially early in treatment. Findings, if positive, will support further development of GBP as an adjunct medication as well as provide an integrated, seamless approach to outpatient prescription opioid-dependence treatment. Ultimately, this work could impact the addiction field by providing both procedural and pharmacological tools for treating prescription opioid dependence that significantly improve outpatient detoxification outcomes and markedly enhance access and transition to NTX therapy. This would shift clinical practice, establishing an effective adjunct regimen for BUP detoxification and an integrated approach for transition to NTX therapy. GBP may also be clinically useful for other situations where opioid withdrawal is a concern.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
NTX Transition Initiation	% of Participants who completed the detox and started the NTX transition	3 days (wk 4 day 1 - week 4 day 3)
Vivitrol Injection Receivers	% of participants starting the NTX transition who received Vivitrol injection

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Name	Affiliation	Role
Alison Oliveto, PhD	University of Arkansas	Principal Investigator
Michael Mancino, MD	University of Arkansas	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Arkansas for Medical Sciences		Little Rock	Arkansas	72205	United States

PubMed Identifier	Type	Citation	Retractions
41401348	Derived	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.

Arm/Group Information

ID	Title	Description
FG000	Gabapentin	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). Gabapentin: N-type calcium channel blocker being examined for its potential efficacy to alleviate opioid withdrawal during buprenorphine-assisted detox and transition to depot naltrexone. Buprenorphine: All participants are stabilized on buprenorphine and then undergo a 10 day taper off buprenorphine. Clonidine: All participants who successfully taper off buprenorphine receive Clonidine (0.1 mg) prior to induction onto oral naltrexone. Naltrexone (oral): 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) Naltrexone (depot): 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.
FG001	Placebo	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). Buprenorphine: All participants are stabilized on buprenorphine and then undergo a 10 day taper off buprenorphine. Clonidine: All participants who successfully taper off buprenorphine receive Clonidine (0.1 mg) prior to induction onto oral naltrexone. Naltrexone (oral): 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) Naltrexone (depot): 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. Placebo: Microcrystalline cellulose

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Gabapentin	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). Gabapentin: N-type calcium channel blocker being examined for its potential efficacy to alleviate opioid withdrawal during buprenorphine-assisted detox and transition to depot naltrexone. Buprenorphine: All participants are stabilized on buprenorphine and then undergo a 10 day taper off buprenorphine. Clonidine: All participants who successfully taper off buprenorphine receive Clonidine (0.1 mg) prior to induction onto oral naltrexone. Naltrexone (oral): 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) Naltrexone (depot): 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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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)

those starting on study medication

Posted

Mean

Standard Deviation

percentage of urine positive samples

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

urine samples

ID	Title	Description
OG000	Gabapentin	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). Gabapentin: N-type calcium channel blocker being examined for its potential efficacy to alleviate opioid withdrawal during buprenorphine-assisted detox and transition to depot naltrexone. Buprenorphine: All participants are stabilized on buprenorphine and then undergo a 10 day taper off buprenorphine. Clonidine: All participants who successfully taper off buprenorphine receive Clonidine (0.1 mg) prior to induction onto oral naltrexone. Naltrexone (oral): 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) Naltrexone (depot): 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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Gabapentin	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). Gabapentin: N-type calcium channel blocker being examined for its potential efficacy to alleviate opioid withdrawal during buprenorphine-assisted detox and transition to depot naltrexone. Buprenorphine: All participants are stabilized on buprenorphine and then undergo a 10 day taper off buprenorphine. Clonidine: All participants who successfully taper off buprenorphine receive Clonidine (0.1 mg) prior to induction onto oral naltrexone. Naltrexone (oral): 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) Naltrexone (depot): 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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 24, 2020	May 10, 2022	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Oct 4, 2021	Jun 29, 2022	SAP_001.pdf
ICF	No	No	Yes	Informed Consent Form	Jul 24, 2020	May 10, 2022	ICF_002.pdf

ID	Term
D064419	Chemically-Induced Disorders
D001523	Mental Disorders

ID	Term
D000588	Amines
D009930	Organic Chemicals
D005680	gamma-Aminobutyric Acid
D000613	Aminobutyrates

ID	Term
D000077206	Gabapentin
D002047	Buprenorphine
D003000	Clonidine
D009271	Naltrexone