Effectiveness of Gabapentin When Used With Naltrexone to Treat Alcohol Dependence Compared to Placebo and Naltrexone Alone

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT00183196
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 150
• Location: 1
• Arms: 3
• Duration (Months): 77
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether, after a period of abstinence, adding 6 weeks of gabapentin (a medication approved to treat seizures) to a standard 16-week naltrexone (an opiate blocking agent approved for the treatment of alcohol dependence) treatment protocol is helpful in decreasing relapse to drinking compared to naltrexone alone or placebo. All participants will receive alcohol counseling.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Dependence	Drug: Naltrexone; Drug: Naltrexone plus Gabapentin; Other: Inactive Placebo	Phase 3

Detailed Description

Subjects will enter the trial after maintaining 4 days of abstinence. During this period multiple assessments will be collected. After entering the double blind treatment portion of the study, they will be evaluated weekly for the first month, then bi-weekly until week 12 and again at week 16. There will be two follow-up visits at weeks 28 and 40. Urinary riboflavin and pill counts will be utilized to determine compliance with the medication regime.

Comparison(s): Naltrexone (50 mg/day) alone for 16-weeks; naltrexone (50 mg/day) for 16-weeks plus gabapentin (up to 1200 mg/day in divided doses) for the first 6 weeks, or inactive placebos. All subjects will receive up to 20 sessions of individual alcohol counseling.

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Gabapentin as an Adjunct to Naltrexone for Alcoholism
• Study Start Date: Jan 1, 2003
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Naltrexone plus placebo	Drug: Naltrexone; Naltrexone (50 mg/day) plus gabapentin placebo in divided doses for the first 6weeks. Naltrexone (50 mg/day) for rest of 16-weeks
Active Comparator: 2 naltrexone + gabapentin	Drug: Naltrexone plus Gabapentin; naltrexone (50 mg/day) for 16-weeks plus gabapentin (up to 1200 mg/day in divided doses) for the first 6 weeks
Sham Comparator: 3 Placebo plus placebo	Other: Inactive Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Time to Relapse to Drinking [16 weeks]

   Time to relapse drinking which is 5 standard drinks perday for males and 4 standard drinks per day for females. Subjects had a minimum of 4 days of abstinence prior to being entered into the protocol.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meet criteria for primary alcohol dependence including loss of control of drinking

• No more than one previous inpatient medical detoxification

• Consumes on average 5 standard drinks for men and 4 standard drinks for women

• Able to maintain sobriety for 4 days (with or without detox medications).

• Able to read and understand questionnaires and Informed Consent

• Lives within 50 miles of the study site

Exclusion Criteria:

• Currently meets DSM-IV criteria for any other psychoactive substance dependency disorder except nicotine dependence

• Ever abused opiates

• Any psychoactive substance abuse, except marijuana and nicotine within the last 30 days as evidenced by subject report, collateral report, or urine drug screen.

• Meets DSM-IV criteria for current Axis I disorder of major depression, panic disorder, obsessive-compulsive disorder, post-traumatic stress syndrome, bipolar affective disorder, dissociative disorder or eating disorder, schizophrenia, or any other psychotic disorder or organic mental disorder.

• Has current suicidal or homicidal ideation

• Need for maintenance or acute treatment with any psychoactive medication including antiseizure medications.

• Current use of disulfiram.

• Clinically significant medical problems, such as cardiovascular, renal, GI or endocrine problem that would impair participation or limit medication ingestion.

• Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at least 3.0 times normal at screening and/or after 5 days of abstinence.

• Sexually active females of child bearing potential who are pregnant (by urine HCG), nursing or who are not using a reliable form of birth control.

• Has current charges pending for a violent crime (not including DUI related offenses).

• Does not have a stable living situation and a reliable source of collateral reporting.

• Has taken an opiate antagonist drug in the last month.

• Has taken gabapentin in the last month or has experienced adverse effects from it at any time in the past.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina, Center for Drug and Alcohol Programs	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Raymond F. Anton, MD, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Raymond F. Anton, Distinguished University Professor, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00183196
• Other Study ID Numbers: NIAAAANT09568-2005a; 5R01AA009568-14; NIH RO1 AA09568
• First Posted: Sep 16, 2005
• Last Update Posted: Jun 7, 2018
• Last Verified: May 1, 2018

• Keywords provided by Raymond F. Anton, Distinguished University Professor, Medical University of South Carolina: Alcohol dependence; Alcoholism; Heavy drinking
• Additional relevant MeSH terms: Alcoholism; Naltrexone; Gabapentin

Study Results

Participant Flow

Arm/Group Title	Naltrexone Plus Gabapentin and CBI	Naltrexone Plus Placebo and CBI	Placebo Plus Placebo Plus CBI
Arm/Group Description	Naltrexone plus gabapentin and CBI individual counseling for 6 weeks then naltrexone and CBI for 10 additional weeks.	Naltrexone plus placebo and CBI individual counseling for 6 weeks then naltrexone and CBI counseling for 10 weeks.	Placebo plus placebo for 6 weeks and CBI individual counseling then placebo and CBI counseling for 10 additional weeks.
Period Title: Overall Study
STARTED	50	50	50
COMPLETED	30	35	32
NOT COMPLETED	20	15	18

Baseline Characteristics

Arm/Group Title	Naltrexone Plus Gabapentin and CBI	Naltrexone Plus Placebo and CBI	Placebo Plus Placebo Plus CBI	Total
Arm/Group Description	Naltrexone plus gabapentin and CBI individual counseling for 6 weeks then naltrexone and CBI for 10 additional weeks.	Naltrexone plus placebo and CBI individual counseling for 6 weeks then naltrexone and CBI counseling for 10 weeks.	Placebo plus placebo for 6 weeks and CBI individual counseling then placebo and CBI counseling for 10 additional weeks.	Total of all reporting groups
Overall Participants	50	50	50	150
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	50 100%	49 98%	49 98%	148 98.7%
>=65 years	0 0%	1 2%	1 2%	2 1.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43 (9.8)	44.4 (10.1)	46.6 (9.0)	44.6 (9.7)
Sex: Female, Male (Count of Participants)
Female	10 20%	11 22%	10 20%	31 20.7%
Male	40 80%	39 78%	40 80%	119 79.3%
Region of Enrollment (participants) [Number]
United States	50 100%	50 100%	50 100%	150 100%

Outcome Measures

1. Primary Outcome

Title	Time to Relapse to Drinking
Description	Time to relapse drinking which is 5 standard drinks perday for males and 4 standard drinks per day for females. Subjects had a minimum of 4 days of abstinence prior to being entered into the protocol.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Subjects who entered the analysis were all people with any drinking data post randomization. There was 2 people in naltrexone plus gabapentin, 1 person in naltrexone alone and 1 person in placebo group that had no post-randomization drinking data and were therefore not included in the intent to treat analysis presented.

Arm/Group Title	Naltrexone Plus Gabapentin and CBI	Naltrexone Plus Placebo and CBI	Placebo Plus Placebo Plus CBI
Arm/Group Description	Naltrexone plus gabapentin and CBI individual counseling for 6 weeks then naltrexone and CBI for 10 additional weeks.	Naltrexone plus placebo and CBI individual counseling for 6 weeks then naltrexone and CBI counseling for 10 weeks.	Placebo plus placebo for 6 weeks and CBI individual counseling then placebo and CBI counseling for 10 additional weeks.
Measure Participants	48	49	49
Mean (Standard Error) [days]	69.9 (6.5)	59.6 (7.6)	57.3 (6.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naltrexone Plus Gabapentin and CBI, Naltrexone Plus Placebo and CBI, Placebo Plus Placebo Plus CBI
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.529
	Confidence Interval	(2-Sided) 95%; .281 to .997
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.0
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Naltrexone Plus Gabapentin and CBI, Naltrexone Plus Placebo and CBI, Placebo Plus Placebo Plus CBI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Regression, Cox
	Comments	percent heavy drinking days at baseline was used as a covariate in the analysis as it was a predictor of overall survival independent of group.

Adverse Events

Arm/Group Title	Naltrexone Plus Gabapentin and CBI		Naltrexone Plus Placebo and CBI		Placebo Plus Placebo Plus CBI
Arm/Group Description	Naltrexone plus gabapentin and CBI individual counseling for 6 weeks then naltrexone and CBI for 10 additional weeks.		Naltrexone plus placebo and CBI individual counseling for 6 weeks then naltrexone and CBI counseling for 10 weeks.		Placebo plus placebo for 6 weeks and CBI individual counseling then placebo and CBI counseling for 10 additional weeks.
All Cause Mortality
	Naltrexone Plus Gabapentin and CBI		Naltrexone Plus Placebo and CBI		Placebo Plus Placebo Plus CBI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Naltrexone Plus Gabapentin and CBI		Naltrexone Plus Placebo and CBI		Placebo Plus Placebo Plus CBI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Naltrexone Plus Gabapentin and CBI		Naltrexone Plus Placebo and CBI		Placebo Plus Placebo Plus CBI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/50 (78%)		29/50 (58%)		31/50 (62%)
Eye disorders
Blurred vision	16/50 (32%)	41	13/50 (26%)	18	7/50 (14%)	25
General disorders
somnolence	39/50 (78%)	106	29/50 (58%)	81	31/50 (62%)	90
Nervous system disorders
Dizziness	20/50 (40%)	33	11/50 (22%)	14	11/50 (22%)	21
Renal and urinary disorders
Premature ejaculation	11/39 (28.2%)	16	4/40 (10%)	4	8/40 (20%)	17

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.