GBN: Improving Treatment Outcomes for Prescription Opioid Dependence

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT02543944
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 117
• Location: 1
• Arms: 2
• Actual Duration (Months): 63.9
• Patients Per Site Per Month: 1.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Drug Dependence	Drug: Gabapentin; Drug: Buprenorphine; Drug: Clonidine; Drug: Naltrexone (oral); Drug: Naltrexone (depot); Drug: Placebo	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Improving Treatment Outcomes for Prescription Opioid Dependence
• Actual Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: May 25, 2021
• Actual Study Completion Date: May 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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).	Drug: Gabapentin; N-type calcium channel blocker being examined for its potential efficacy to alleviate opioid withdrawal during buprenorphine-assisted detoxification and transition to depot naltrexone.; Drug: Buprenorphine; All participants are stabilized on buprenorphine and then undergo a 10 day taper off buprenorphine.; Drug: Clonidine; All participants who successfully taper off buprenorphine receive Clonidine (0.1 mg) prior to induction onto oral naltrexone.; Drug: 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); Drug: 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 Comparator: 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).	Drug: Buprenorphine; All participants are stabilized on buprenorphine and then undergo a 10 day taper off buprenorphine.; Drug: Clonidine; All participants who successfully taper off buprenorphine receive Clonidine (0.1 mg) prior to induction onto oral naltrexone.; Drug: 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); Drug: 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.; Drug: Placebo; Microcrystalline cellulose

Outcome Measures

Primary Outcome Measures

1. Detoxification Phase: Changes in Percent of Illicit Opioid-positive Urine Samples Over Time [Week 1 day 1 (study entry) through Week 4 day 1 (first day of NTX transition)]

   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)

Secondary Outcome Measures

1. NTX Transition Initiation [3 days (wk 4 day 1 - week 4 day 3)]

   % of Participants who completed the detox and started the NTX transition

2. Vivitrol Injection Receivers [5 days (week 4 day 1 to week 4 day 5)]

   % of participants starting the NTX transition who received Vivitrol injection

3. Detox Phase Completers [3 weeks (week 1-3)]

   % of enrolled participants who completed the Detox Phase

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. be between the ages of 18-65

2. be available to attend clinic 6 days a week for approximately 30-60 minutes per day during the first 4 3 weeks

3. 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.

4. submit a urine sample negative for benzodiazepines or barbiturates prior to starting the study.

Exclusion Criteria:

1. report having had a severe adverse reaction to study medications

2. 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)

3. have a major psychiatric disorder (psychosis, schizophrenia, bipolar)

4. have major depression or anxiety disorder requiring psychoactive medication (as determined by physician)

5. physiological dependence on alcohol or drugs other than opioids, tobacco or marijuana (as determined by physician assessment)

6. are pregnant, plan to become pregnant or have inadequate birth control, if relevant

7. report ongoing use of over-the-counter or prescription drug (including Maalox) that would have major interaction with study drugs

8. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Alison Oliveto, PhD, University of Arkansas
• Principal Investigator: Michael Mancino, MD, University of Arkansas

Study Documents (Full-Text)

• Study Protocol - Jul 24, 2020
• Statistical Analysis Plan - Oct 4, 2021
• Informed Consent Form - Jul 24, 2020

More Information

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT02543944
• Other Study ID Numbers: 203970; R01DA039088
• First Posted: Sep 7, 2015
• Last Update Posted: Jul 28, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Opioid-Related Disorders; Substance-Related Disorders; Clonidine; Naltrexone; Buprenorphine; Gabapentin

Study Results

Participant Flow

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	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.	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
Period Title: Phase 1: GBN/BUP Induction and BUP Detox
STARTED	60	57
COMPLETED	41	34
NOT COMPLETED	19	23
Period Title: Phase 1: GBN/BUP Induction and BUP Detox
STARTED	33	29
COMPLETED	12	12
NOT COMPLETED	21	17
Period Title: Phase 1: GBN/BUP Induction and BUP Detox
STARTED	12	12
COMPLETED	7	3
NOT COMPLETED	5	9

Baseline Characteristics

Arm/Group Title	Gabapentin	Placebo	Total
Arm/Group Description	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.	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	Total of all reporting groups
Overall Participants	60	57	117
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.0 (8.3)	32.5 (7.3)	32.7 (7.8)
Sex: Female, Male (Count of Participants)
Female	28 46.7%	25 43.9%	53 45.3%
Male	32 53.3%	32 56.1%	64 54.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 5%	4 7%	7 6%
Not Hispanic or Latino	57 95%	53 93%	110 94%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.7%	0 0%	1 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 10%	6 10.5%	12 10.3%
White	52 86.7%	50 87.7%	102 87.2%
More than one race	1 1.7%	1 1.8%	2 1.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	60 100%	57 100%	117 100%
Education Level (Count of Participants)
Less than High School	8 13.3%	4 7%	12 10.3%
High School/Some College/Vocational School	43 71.7%	46 80.7%	89 76.1%
College Degree or higher	8 13.3%	5 8.8%	13 11.1%
Unknown	1 1.7%	2 3.5%	3 2.6%

Outcome Measures

1. Primary Outcome

Title	Detoxification Phase: Changes in Percent of Illicit Opioid-positive Urine Samples Over Time
Description	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)
Time Frame	Week 1 day 1 (study entry) through Week 4 day 1 (first day of NTX transition)

Outcome Measure Data

Analysis Population Description

those starting on study medication

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	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.	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
Measure Participants	60	57
Measure urine samples	455	421
Mean (Standard Deviation) [percentage of urine positive samples]	35.0 (36.7)	41.6 (38.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	-0.0944
	Confidence Interval	(2-Sided) 95%; -0.72 to 0.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

2. Secondary Outcome

Title	NTX Transition Initiation
Description	% of Participants who completed the detox and started the NTX transition
Time Frame	3 days (wk 4 day 1 - week 4 day 3)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	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.	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
Measure Participants	41	34
Count of Participants [Participants]	33 55%	29 50.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Vivitrol Injection Receivers
Description	% of participants starting the NTX transition who received Vivitrol injection
Time Frame	5 days (week 4 day 1 to week 4 day 5)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	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.	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
Measure Participants	33	29
Count of Participants [Participants]	12 20%	12 21.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.16
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Detox Phase Completers
Description	% of enrolled participants who completed the Detox Phase
Time Frame	3 weeks (week 1-3)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	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.	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
Measure Participants	60	57
Count of Participants [Participants]	41 68.3%	34 59.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	.96
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Gabapentin		Placebo
Arm/Group Description	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.		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
All Cause Mortality
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/57 (0%)
Serious Adverse Events
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/60 (71.7%)		37/57 (64.9%)
Cardiac disorders
Elevated heart rate	1/60 (1.7%)	1	2/57 (3.5%)	2
Eye disorders
Dry eyes	0/60 (0%)	0	1/57 (1.8%)	1
Burning sensation in eyes	1/60 (1.7%)	1	0/57 (0%)	0
Blood shot eye	1/60 (1.7%)	1	0/57 (0%)	0
Changes in vision	3/60 (5%)	3	0/57 (0%)	0
Gastrointestinal disorders
Nausea	0/60 (0%)	0	5/57 (8.8%)	5
Vomiting	4/60 (6.7%)	4	3/57 (5.3%)	3
Heartburn	1/60 (1.7%)	1	0/57 (0%)	0
Stomach cramps	0/60 (0%)	0	1/57 (1.8%)	1
Abdominal pain/soreness	2/60 (3.3%)	2	0/57 (0%)	0
Loose, pale stools	0/60 (0%)	0	1/57 (1.8%)	1
Diarrhea	4/60 (6.7%)	4	2/57 (3.5%)	2
Constipation	3/60 (5%)	3	2/57 (3.5%)	2
Withdrawal sx: Nausea	2/60 (3.3%)	2	6/57 (10.5%)	6
Withdrawal sx: Vomiting	2/60 (3.3%)	2	4/57 (7%)	4
Withdrawal sx: Diarrhea	2/60 (3.3%)	3	9/57 (15.8%)	9
Withdrawal sx: Constipation	0/60 (0%)	0	0/57 (0%)	0
General disorders
Sedation/drowsiness	8/60 (13.3%)	8	4/57 (7%)	4
Listlessness/loss of energy	1/60 (1.7%)	1	0/57 (0%)	0
Fatigue	1/60 (1.7%)	1	3/57 (5.3%)	3
Weakness	0/60 (0%)	0	1/57 (1.8%)	1
Insomnia	1/60 (1.7%)	1	2/57 (3.5%)	2
Sleep disturbance/sleep walking	1/60 (1.7%)	1	0/57 (0%)	0
Restlessness	1/60 (1.7%)	1	0/57 (0%)	0
Tooth pain	0/60 (0%)	0	1/57 (1.8%)	1
Changes in equilibrium	0/60 (0%)	0	2/57 (3.5%)	2
Fall	1/60 (1.7%)	1	0/57 (0%)	0
Headache	7/60 (11.7%)	7	8/57 (14%)	8
Dry mouth	3/60 (5%)	3	2/57 (3.5%)	2
Changes in taste	1/60 (1.7%)	1	1/57 (1.8%)	1
Hiccups	1/60 (1.7%)	1	0/57 (0%)	0
Edema/swelling	1/60 (1.7%)	1	1/57 (1.8%)	1
Hot/cold sweats	0/60 (0%)	0	1/57 (1.8%)	1
Continuously hot all day	0/60 (0%)	0	1/57 (1.8%)	1
Fever	0/60 (0%)	0	1/57 (1.8%)	1
Sexual side effect	1/60 (1.7%)	1	0/57 (0%)	0
Auditory and visual hallucinations	1/60 (1.7%)	1	0/57 (0%)	0
Confusion/Disorientation	1/60 (1.7%)	1	0/57 (0%)	0
Irritability	2/60 (3.3%)	2	1/57 (1.8%)	1
Agitation	1/60 (1.7%)	1	0/57 (0%)	0
Anger	1/60 (1.7%)	1	0/57 (0%)	0
Withdrawal symptoms	13/60 (21.7%)	14	19/57 (33.3%)	25
Withdrawal symptoms: not specified	3/60 (5%)	3	1/57 (1.8%)	1
Withdrawal sx: Related to dehydration	0/60 (0%)	0	1/57 (1.8%)	1
Withdrawal sx: Leg pain	0/60 (0%)	0	2/57 (3.5%)	2
Withdrawal sx: Muscle cramps	1/60 (1.7%)	1	1/57 (1.8%)	1
Withdrawal sx: Bone/muscle pain	2/60 (3.3%)	2	2/57 (3.5%)	2
Withdrawal sx: Stomach cramps	2/60 (3.3%)	3	9/57 (15.8%)	9
Withdrawal sx: Abdominal pain	0/60 (0%)	0	1/57 (1.8%)	1
Withdrawal sx: Loss of appetite	0/60 (0%)	0	1/57 (1.8%)	1
Withdrawal sx: Runny nose/sneezing and/or watery eyes	1/60 (1.7%)	1	3/57 (5.3%)	3
Withdrawal sx: Chills	1/60 (1.7%)	1	1/57 (1.8%)	1
Withdrawal sx: Hot/cold sweats	0/60 (0%)	0	5/57 (8.8%)	6
Withdrawal sx: Excessive sweating	2/60 (3.3%)	2	3/57 (5.3%)	3
Withdrawal sx: Fatigue	0/60 (0%)	0	1/57 (1.8%)	1
Withdrawal sx: Sedation	0/60 (0%)	0	2/57 (3.5%)	2
Withdrawal sx: Nodding off	0/60 (0%)	0	0/57 (0%)	0
Withdrawal sx: Insomnia	2/60 (3.3%)	2	3/57 (5.3%)	3
Withdrawal sx: Restlessness	1/60 (1.7%)	1	3/57 (5.3%)	3
Withdrawal sx: Yawning	1/60 (1.7%)	1	2/57 (3.5%)	2
Withdrawal sx: Stretching	1/60 (1.7%)	1	0/57 (0%)	0
Withdrawal sx: Muscle twiches/jerks	0/60 (0%)	0	1/57 (1.8%)	1
Withdrawal sx: Shakes/tremors	2/60 (3.3%)	2	1/57 (1.8%)	1
Withdrawal sx: Tingling extremities	1/60 (1.7%)	1	0/57 (0%)	0
Withdrawal sx: Headache	1/60 (1.7%)	1	1/57 (1.8%)	1
Withdrawal sx: Lightheaded	0/60 (0%)	0	1/57 (1.8%)	1
Withdrawal sx: Short of breath	0/60 (0%)	0	1/57 (1.8%)	1
Withdrawal sx: Dizziness	1/60 (1.7%)	1	1/57 (1.8%)	1
Withdrawal sx: Clammy feet/hands	0/60 (0%)	0	1/57 (1.8%)	1
Withdrawal sx: Gooseflesh	0/60 (0%)	0	1/57 (1.8%)	1
Withdrawal sx: Depression	1/60 (1.7%)	1	1/57 (1.8%)	1
Withdrawal sx: Anxiety	1/60 (1.7%)	1	2/57 (3.5%)	2
Withdrawal sx: Irritability	1/60 (1.7%)	1	1/57 (1.8%)	1
Infections and infestations
Diagnosis of shingles	0/60 (0%)	0	1/57 (1.8%)	1
Infection	1/60 (1.7%)	1	0/57 (0%)	0
Flu virus	1/60 (1.7%)	1	0/57 (0%)	0
Injury, poisoning and procedural complications
Injection site reaction	1/60 (1.7%)	1	1/57 (1.8%)	1
Bruising/laceration	2/60 (3.3%)	2	2/57 (3.5%)	3
Musculoskeletal and connective tissue disorders
Muscle/skeletal pain/discomfort	4/60 (6.7%)	5	1/57 (1.8%)	2
Nervous system disorders
Muscle twitches/tremors	5/60 (8.3%)	6	2/57 (3.5%)	2
Tingling extremities	1/60 (1.7%)	1	0/57 (0%)	0
Psychiatric disorders
Symptoms of anxiety	1/60 (1.7%)	1	1/57 (1.8%)	1
Dysphoria	1/60 (1.7%)	1	0/57 (0%)	0
Symptoms of depression and/or anhedonia	1/60 (1.7%)	1	3/57 (5.3%)	3
Suicidal ideation	1/60 (1.7%)	1	1/57 (1.8%)	1
Renal and urinary disorders
Urination changes	6/60 (10%)	7	1/57 (1.8%)	1
Bright colored urine	1/60 (1.7%)	1	0/57 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory symptoms	2/60 (3.3%)	2	3/57 (5.3%)	3
Skin and subcutaneous tissue disorders
Itching	0/60 (0%)	0	2/57 (3.5%)	2
Rash on knees	0/60 (0%)	0	1/57 (1.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.