VGB: Vigabatrin for Cocaine and Alcohol Dependence

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01335867
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 32
• Location: 1
• Arms: 2
• Duration (Months): 32
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness of vigabatrin at reducing drug and alcohol use in individuals addicted to cocaine and alcohol. Vigabatrin is approved for the treatment of seizures. It has not been proven to be effective for the treatment of alcohol or cocaine dependence.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism; Cocaine Dependence	Drug: Vigabatrin; Drug: Placebo	Phase 2

Detailed Description

The hypotheses in the proposed study will be tested with a 2-group design to assess the efficacy of vigabatrin compared to placebo. We will follow NIAAA's COMBINE Medical Management (MM) manual in weekly dispensing medications, safety checks and medication adherence. The psychosocial treatment will be Cognitive Behavioral Coping Skills Therapy (CBT). Subjects will be 60 men and women with current DSM-IV diagnoses of both cocaine and alcohol dependence who will be randomized to vigabatrin or placebo (30 subjects per group). All subjects will receive weekly sessions of CBT. The study length for each subject is comprised of a1-3 weeks of screening and baseline evaluations, an 8-week double-blind, placebo-controlled trial with CBT (medication phase), and one follow-up visit 12 weeks after starting study medication.

Study medication will be initiated in Week 2. The research physician will explain the dosing regimen and subjects will be randomly assigned to receive either vigabatrin or identical placebo tablets. Subjects will receive 1 gram of vigabatrin or identical placebo tablets on medication days 1-3 then 1.5 grams or identical placebo tablets on days 4-7. The dose ids increased to 2 grams in week 2, 3 grams in weeks 4-7 and then reduced to 2 grams days 50-53, and to 1 gram on days 54-56

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Double-Blind, Placebo-Controlled, Pilot Trial of Vigabatrin for the Treatment of Cocaine and Alcohol Dependence
• Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vigabatrin Vigabatrin titrated to 3 grams daily for 8 weeks	Drug: Vigabatrin; Vigabatrin escalated to 3 grams daily for 8 weeks; Other Names: Sabril
Placebo Comparator: Placebo Identical placebo daily for three weeks	Drug: Placebo; Placebo pills; Other Names: placebo vigabatrin

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Reduction in Cocaine Use [last 3 weeks of the trial]

   The primary outcome measure for reduction in cocaine use will be the number of benzoylecgonine (BE) negative urine samples. The main outcome is the number of participants in each group who reported all BE negative urine samples in the last three weeks of the trial.

2. Proportion of Heavy Drinking Days [8 weeks]

   The primary outcome measure for reduction in alcohol use will be recorded using the Timeline Followback method.

Secondary Outcome Measures

1. Measures of Cocaine Craving [8 weeks]

   Measures of cocaine craving at the end of the trial will be measured using the Brief Substance Craving Ccale. Craving intensity + Craving frequency + Craving Duration each measured on a 4 point scale. Sum of the three scales was overall craving composite. Higher numbers meaning greater craving. Maximum score 12 minimum 0.

2. Disease Severity and Improvement [8 weeks]

   Number of subjects in each group rated as improved or very much improved at the end of the trial

3. Cocaine Withdrawal Severity [8 weeks]

   Measure of cocaine withdrawal severity will include Cocaine Selective Severity Assessment scores. Minimum score is 0 Maximum score is 119 Higher score is indicative of worse cocaine withdrawal symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male and females, 18 years of age or older.

2. Meets DSM-IV criteria for current diagnoses of cocaine and alcohol dependence, determined by the SCID-IV.

3. Used cocaine in the past 30 days and used no less than $200 of cocaine in a consecutive 30 day period over the 90 day period prior to intake. Meets the following drinking criteria as measured by the Timeline Followback (TLFB) (Sobell 1995) a drank within 30 days of intake day, b. reports a minimum of 48 standard alcoholic (avg. 12 drinks/wk) in a consecutive 30-day period over the 90-day period prior to starting intake (i.e., a minimum of 40% days drinking), and c. has 2 or more days of heavy drinking (defined as greater than 4 drinks per day in males and greater than 3 drinks per day in females) in this same pre-treatment period.

4. Three consecutive days of abstinence from alcohol directly prior to the day of randomization, determined by self-reports and confirmed by negative breathalyzer tests, and a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR) (Sullivan and Sellers 1989) score below eight. Subjects will be given 2 additional weeks beyond the screening week to attain the appropriate period of alcohol abstinence prior to randomization.

5. Have a verifiable address of principal residence, lives a commutable distance from the TRC and agrees to attend all research visits including follow-up visits.

6. Speaks, understands, and prints in English

7. Ability to give informed consent

Exclusion Criteria:

1. Meets DSM IV criteria for dependence on any substance other than cocaine and alcohol (except nicotine and cannabis), determined by the SCID. Needs treatment with any psychoactive medications including any anti-seizure medications (with the exception of diphenhydramine used sparingly, if necessary, for sleep).

2. Meets current or lifetime DSM-IV criteria for schizophrenia or any psychotic disorder or organic mental disorder. Subject meets current DSM-IV diagnosis of any other clinically significant psychiatric disorder that will interfere with study participation as determined by the principal investigator.

3. Has evidence of a history of significant hematological, pulmonary, endocrine, cardiovascular, renal or gastrointestinal disease.

4. Severe physical or medical illnesses such as AIDS, active hepatitis, significant hepatocellular injury as evidenced by elevated total bilirubin levels (>1.3 mg/dl), or elevated levels (over 4.5x normal) of aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT). Patients with Gilberts Syndrome will not be excluded.

5. Use of an investigational medication in the 30 days prior to randomization.

6. History of prior treatment with vigabatrin

7. History of prior treatment with drugs with known retinotoxicity

8. History of visual field defects or predisposing factors, including glaucoma, severe myopia, retinal disorders, cataracts, diabetes, or uncontrolled hypertension.

9. Is female and tests positive on a pregnancy test, is contemplating pregnancy in the next 6 months, is nursing, or is not using an effective contraceptive method (if relevant). Acceptable methods of contraception include barrier methods (diaphragm or condom with spermicide, female condom), intrauterine progesterone contraceptive system, levonorgrestrel implant, and medroxyprogesterone acetate contraceptive injection, copper IUD, vaginal contraceptive film, cervical cap, contraceptive foam, hormonal vaginal contraceptive ring (NuvaRing®) or oral contraceptives.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania, Treatment Research Center	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Kyle M Kampman, M.D., University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Pennsylvania Center for Studies of Addictions

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01335867
• Other Study ID Numbers: 812864; P50DA012756
• First Posted: Apr 14, 2011
• Last Update Posted: Sep 6, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Alcoholism; Cocaine-Related Disorders; Vigabatrin

Study Results

Participant Flow

Arm/Group Title	Vigabatrin	Placebo
Arm/Group Description	Vigabatrin: Vigabatrin escalated to 3 grams daily for 8 weeks	Placebo: Placebo pills
Period Title: Overall Study
STARTED	16	16
COMPLETED	9	12
NOT COMPLETED	7	4

Baseline Characteristics

Arm/Group Title	Vigabatrin	Placebo	Total
Arm/Group Description	Vigabatrin: Vigabatrin escalated to 3 grams daily for 8 weeks	Placebo: Placebo pills	Total of all reporting groups
Overall Participants	16	16	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 100%	16 100%	32 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46 (7.97)	48 (6.81)	47 (7.35)
Sex: Female, Male (Count of Participants)
Female	4 25%	6 37.5%	10 31.3%
Male	12 75%	10 62.5%	22 68.8%
Region of Enrollment (participants) [Number]
United States	16 100%	16 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Reduction in Cocaine Use
Description	The primary outcome measure for reduction in cocaine use will be the number of benzoylecgonine (BE) negative urine samples. The main outcome is the number of participants in each group who reported all BE negative urine samples in the last three weeks of the trial.
Time Frame	last 3 weeks of the trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vigabatrin	Placebo
Arm/Group Description	Vigabatrin: Vigabatrin escalated to 3 grams daily for 12 weeks	Placebo: Placebo pills
Measure Participants	16	16
Number [participants]	0 0%	2 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vigabatrin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.14
	Comments
	Method	Chi-squared
	Comments

2. Primary Outcome

Title	Proportion of Heavy Drinking Days
Description	The primary outcome measure for reduction in alcohol use will be recorded using the Timeline Followback method.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vigabatrin	Placebo
Arm/Group Description	Vigabatrin: Vigabatrin escalated to 3 grams daily for 8 weeks	Placebo: Placebo pills
Measure Participants	16	16
Mean (Standard Deviation) [proportion of heavy drinking days]	.26 (.18)	.20 (.25)

3. Secondary Outcome

Title	Measures of Cocaine Craving
Description	Measures of cocaine craving at the end of the trial will be measured using the Brief Substance Craving Ccale. Craving intensity + Craving frequency + Craving Duration each measured on a 4 point scale. Sum of the three scales was overall craving composite. Higher numbers meaning greater craving. Maximum score 12 minimum 0.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

subjects receiving vigabatrin or placebo who were available at the end of the trial to provide data.

Arm/Group Title	Vigabatrin	Placebo
Arm/Group Description	vigabatrin 3 grams daily for 12 weeks	placebo capsules
Measure Participants	9	8
Mean (Standard Deviation) [score on a scale]	1.44 (2.3)	0.38 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vigabatrin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.24
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Disease Severity and Improvement
Description	Number of subjects in each group rated as improved or very much improved at the end of the trial
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vigabatrin	Placebo
Arm/Group Description	Vigabatrin titrated to 3 grams daily for 12 weeks Vigabatrin: Vigabatrin escalated to 3 grams daily for 8 weeks	Identical placebo daily for 12 weeks Placebo: Placebo pills
Measure Participants	16	16
Count of Participants [Participants]	5 31.3%	2 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vigabatrin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.20
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Cocaine Withdrawal Severity
Description	Measure of cocaine withdrawal severity will include Cocaine Selective Severity Assessment scores. Minimum score is 0 Maximum score is 119 Higher score is indicative of worse cocaine withdrawal symptoms.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

subjects receiving vigabatrin or placebo who were available at the end of the trial to provide data.

Arm/Group Title	Vigabatrin	Placebo
Arm/Group Description	Vigabatrin titrated to 3 grams daily for 8 weeks Vigabatrin: Vigabatrin escalated to 3 grams daily for 8 weeks	Identical placebo daily for three weeks Placebo: Placebo pills
Measure Participants	10	11
Mean (Standard Deviation) [score on a scale]	8.0 (8.1)	6.5 (6.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vigabatrin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.64
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Arm/Group Title	Vigabatrin		Placebo
Arm/Group Description	Vigabatrin: Vigabatrin escalated to 3 grams daily for 8 weeks		Placebo: Placebo pills
All Cause Mortality
	Vigabatrin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vigabatrin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Vigabatrin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/16 (62.5%)		13/16 (81.3%)
Gastrointestinal disorders
Nausea	2/16 (12.5%)		0/16 (0%)
Vomiting	0/16 (0%)		2/16 (12.5%)
General disorders
Headache	2/16 (12.5%)		0/16 (0%)
Dry Mouth	2/16 (12.5%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	2/16 (12.5%)		0/16 (0%)
Sore Knees	0/16 (0%)		2/16 (12.5%)
Respiratory, thoracic and mediastinal disorders
URI Symptoms	2/16 (12.5%)		3/16 (18.8%)
Sinus Congestion	0/16 (0%)		2/16 (12.5%)
Cough	0/16 (0%)		2/16 (12.5%)
Skin and subcutaneous tissue disorders
Nasal Congestion	0/16 (0%)		2/16 (12.5%)

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.