TOP2: Topiramate for Alcohol and Cocaine Dependence

• Sponsor: Kyle Kampman (Other)
• Overall Status: Completed
• CT.gov ID: NCT00167245
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 170
• Location: 1
• Arms: 2
• Duration (Months): 69
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

The primary purpose of this study is to test the effectiveness of topiramate for the treatment of combined alcohol and cocaine dependence. Topiramate 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: Topiramate; Drug: placebo	Phase 2

Detailed Description

The purpose of this study is to evaluate the efficacy of 300 mg/day of topiramate for the treatment of 200 treatment-seeking alcohol dependent outpatients with comorbid cocaine dependence in a double-blind, placebo-controlled 14-week trial, with a 6-month follow-up (3 months after completing medications).

Study Design

• Study Type: Interventional
• Actual Enrollment: 170 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Double-blind, Placebo-Controlled, Pilot Trial of Topiramate for Alcohol and Comorbid Cocaine Dependence
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Topiramate topiramate capsules dose titrated up to 300 mg daily	Drug: Topiramate; 300mg/day for 13 weeks; Other Names: topamax
Placebo Comparator: Placebo placebo capsules identical in appearance to the topiramate capsules	Drug: placebo; placebo pills

Outcome Measures

Primary Outcome Measures

1. Percent of Participants Abstinent From Cocaine During Last 3 Weeks of 13 Week Trial [Last 3 weeks of 13 week trial]

   Samples were analyzed for benzoylecgonine by fluorescent polarization assay. Samples containing equal to or greater than 300 ng/ml of benzoylecgonine were considered to be positive for cocaine.

2. Number of Heavy Drinking Days [13 weeks]

   Heavy drinking days, defined as more than 4 standard drinks for men and 3 standard drinks for women

Secondary Outcome Measures

1. Cocaine Withdrawal Symptoms Measured by Cocaine Selective Severity Assessment. [13 weeks]

   Total cssa score at the end of the medication phase of the trial. The CSSA is a measure of cocaine withdrawal severity. The minimum score is 0 the maximum score is 119. Higher score means more severe cocaine withdrawal symptoms

2. The Penn Alcohol Craving Scale [13 weeks]

   This Scale measures alcohol craving. The maximum score is 30, the minimum score is 0. Higher scores are indicative of more severe alcohol craving.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male and females, 18 years or older.

• Meets DSM(Diagnostic and Statistical Manual)-IV criteria for current diagnoses of cocaine and alcohol dependence, determined by the SCID (Structured Clinical Interview for the DSM)-IV.

• In the past 30 days, used no less than $200-worth of cocaine and meets the following drinking criteria as measured by the Timeline Followback (TLFB) (Sobell and Sobell,

1. 1. drank within 30 days of intake day, b. reports a minimum of 48 standard alcoholic drinks (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 5 or more drinks per day in males and 4 or more drinks per day in females) in this same pre-treatment period.

• Two consecutive days of abstinence from cocaine and alcohol, determined by self-reports and confirmed by negative urine toxicology screens, a negative breathalyzer tests, and collateral report, a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR) (Sullivan et al., 1989) score below eight,. Subjects will be encouraged to achieve 3 consecutive days of abstinence, however, subjects who have achieved 2 consecutive days of abstinence will be included with the approval of the principal investigator. We anticipate that these subjects will comprise less than 5% of total enrolled subjects. Subjects will be given 2 additional weeks beyond the screening week to attain the appropriate period of cocaine and alcohol abstinence prior to randomization.

• Lives a commutable distance from the Treatment Research Center (TRC) and agrees to attend all research visits including follow-up visits.

• Speaks, understands, and prints in English.

Exclusion Criteria:

• Abstinent from cocaine or alcohol for 30 consecutive days prior to signing consent form.

• 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 Benadryl used sparingly, if necessary, for sleep).

• Current use of phenytoin or any drug of similar class.

• Meets 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.

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

• Severe physical or medical illnesses such as AIDS, active hepatitis, significant hepatocellular injury as evidenced by elevated bilirubin levels (>1.3), or elevated levels (over 3.5x normal) of aspartate aminotransferase (AST), and serum glutamic-pyruvic transaminase (SGPT) after the required 3 days of abstinence, or severe renal disease, severe respiratory diseases or severe diarrhea with resulting metabolic acidosis, serum bicarbonate (< 20 milliequivalent (mEq)/L)

• History of epilepsy or seizure disorder.

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

• History of nephrolithiasis (kidney stones).

• History of hypersensitivity to topiramate.

• 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, intrauterine progesterone contraceptive system, levonorgestrel implant, and medroxyprogesterone acetate contraceptive injection).

• Current use of a carbonic anhydrase inhibitor.

• A history of glaucoma

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

• Kyle Kampman
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Kyle M Kampman, MD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kyle Kampman, Sponsor-Investigator, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00167245
• Other Study ID Numbers: 801385; R01AA014657
• First Posted: Sep 14, 2005
• Last Update Posted: Jul 7, 2020
• Last Verified: Jul 1, 2019

• Keywords provided by Kyle Kampman, Sponsor-Investigator, University of Pennsylvania: Topiramate; alcoholism; cocaine dependence
• Additional relevant MeSH terms: Alcoholism; Cocaine-Related Disorders; Topiramate

Study Results

Participant Flow

Recruitment Details	Recruitment for this study began on 11/1/2004 and ended five years later in November 2009. Participants were treatment-seeking cocaine and alcohol users recruited at the UPenn Treatment Research Center.

Arm/Group Title	Topiramate	Placebo
Arm/Group Description	topiramate Topiramate : 300mg/day for 13 weeks	placebo : placebo pills
Period Title: Overall Study
STARTED	83	87
COMPLETED	54	46
NOT COMPLETED	29	41

Baseline Characteristics

Arm/Group Title	Group 1	Group 2	Total
Arm/Group Description	topiramate Topiramate : 300mg/day for 13 weeks	placebo : placebo pills	Total of all reporting groups
Overall Participants	83	87	170
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	83 100%	87 100%	170 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45 (7.0)	43 (8.0)	44 (7.0)
Sex: Female, Male (Count of Participants)
Female	18 21.7%	18 20.7%	36 21.2%
Male	65 78.3%	69 79.3%	134 78.8%
Region of Enrollment (participants) [Number]
United States	83 100%	87 100%	170 100%

Outcome Measures

1. Primary Outcome

Title	Percent of Participants Abstinent From Cocaine During Last 3 Weeks of 13 Week Trial
Description	Samples were analyzed for benzoylecgonine by fluorescent polarization assay. Samples containing equal to or greater than 300 ng/ml of benzoylecgonine were considered to be positive for cocaine.
Time Frame	Last 3 weeks of 13 week trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topirmate	Placebo
Arm/Group Description	topiramate Topiramate : 300mg/day for 13 weeks	placebo : placebo pills
Measure Participants	83	87
Number [Percent of participants]	17 20.5%	6 6.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topirmate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Chi-squared
	Comments

2. Primary Outcome

Title	Number of Heavy Drinking Days
Description	Heavy drinking days, defined as more than 4 standard drinks for men and 3 standard drinks for women
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topiramate	Placebo
Arm/Group Description	topiramate Topiramate : 300mg/day for 13 weeks	placebo : placebo pills
Measure Participants	54	46
Mean (Standard Error) [number of heavy drinking days]	5.21 (.58)	6.10 (.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topirmate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	Generalized Estimating Equations
	Comments

3. Secondary Outcome

Title	Cocaine Withdrawal Symptoms Measured by Cocaine Selective Severity Assessment.
Description	Total cssa score at the end of the medication phase of the trial. The CSSA is a measure of cocaine withdrawal severity. The minimum score is 0 the maximum score is 119. Higher score means more severe cocaine withdrawal symptoms
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

Subjects present during the last week of the trial

Arm/Group Title	Group 1	Group 2
Arm/Group Description	topiramate Topiramate: 300mg/day for 13 weeks	placebo: placebo pills
Measure Participants	52	47
Mean (Standard Deviation) [score on a scale]	9.9 (9.5)	8.4 (8.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topirmate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -2.1 to 5.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	The Penn Alcohol Craving Scale
Description	This Scale measures alcohol craving. The maximum score is 30, the minimum score is 0. Higher scores are indicative of more severe alcohol craving.
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2
Arm/Group Description	topiramate Topiramate: 300mg/day for 13 weeks	placebo: placebo pills
Measure Participants	83	87
Mean (Standard Deviation) [score on a scale]	7.90 (6.86)	9.29 (6.48)

Adverse Events

Time Frame	13 weeks
Adverse Event Reporting Description	adverse events queried at each visit
Arm/Group Title	Topiramate		Placebo
Arm/Group Description	topiramate Topiramate : 300mg/day for 13 weeks		placebo : placebo pills
All Cause Mortality
	Topiramate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/83 (0%)		0/87 (0%)
Serious Adverse Events
	Topiramate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/83 (0%)		0/87 (0%)
Other (Not Including Serious) Adverse Events
	Topiramate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/83 (55.4%)		24/87 (27.6%)
General disorders
Sedation	17/83 (20.5%)		15/87 (17.2%)
Headache	6/83 (7.2%)		3/87 (3.4%)
Dry Mouth	6/83 (7.2%)		3/87 (3.4%)
Skin and subcutaneous tissue disorders
Paresthesias	17/83 (20.5%)		3/87 (3.4%)

Limitations/Caveats

The total number of subjects was relatively small and thus the results should be considered preliminary. The study drop-out rate was formidable, though it was comparable with most trials involving cocaine-dependent patients.

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.