The Effects of Topiramate on Alcohol Use in Alcohol Dependent Subjects

• Sponsor: Boston University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00329407
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 57
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This investigation will assess the effectiveness of topiramate in reducing ethanol consumption by alcohol dependent subjects. It also will seek to establish whether topiramate can be safely used in this population including whether it might be subject to abuse by alcohol dependent individuals.

A secondary goal of this study is to assess the effects of topiramate on verbal fluency during treatment for alcohol dependence.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism	Drug: Topiramate (Topamax)	Phase 4

Detailed Description

Alcoholism is a disorder that produces extensive morbidity and mortality. Substantial progress has been made in the development of medications that can help to promote abstinence in alcohol dependent individuals. However, investigations of the most promising drugs, particularly naltrexone and acamprosate, suggest that these agents have at best moderate efficacy and there is a great need for additional medications for the treatment of alcoholism.

The results of a recent study suggest that the administration of the anticonvulsant agent ,topiramate helps alcoholic individuals to maintain abstinence (Johnson et al., 2003). The objectives of this study is to determine whether topiramate will reduce the consumption of alcohol in subjects dependent on this substance, as has been previously reported.Other study objectives are to assess the abuse liability properties of topiramate in alcohol dependent subjects and to examine the effects of chronic topiramate administration on cognitive functioning.

This will be a thirteen week long open label clinical trial of the effects of topiramate administration on ethanol consumption by alcohol dependent subjects.

Subjects will be asked to provide informed consent and then will be screened on the same day to determine if they meet study eligibility criteria. Subjects will be asked to return to provide two urines over the following week.

Baseline measures of mood, craving, withdrawal, cognitive functioning and physical health will be obtained. In the afternoon they will receive their first dose of medication. Their responses to this medication challenge will be assessed over a 3-hour period.

During the drug treatment phase subjects will be asked to come to the clinic weekly for assessment and manual guided therapy during weeks 1-4 and biweekly during weeks 6-8. On day 85 subjects will be seen at the clinic for a termination visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: Sep 1, 2003
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Active Comparator: Topiramate Treatment In this open label non-placebo controlled trial all subjects received topiramate, the active medication. Medication Dosing Schedule: Days 1-3 50 mg q PM Days 4-7 50 mg BID Days 8-11 50 mg q AM & 100 mg q PM Days 12-15 100mg BID Days 16-19 100 mg q AM & 150 mg q PM Days 20-23 150 mg BID Days 24-27 150 mg qAM & 200 mg q PM Days 28-70 200 mg BID Days 71-77 150 mg BID Days 78-84 100mg BID Days 85-87 50 mg BID Days 88-91 50 mg qPM

Drug: Topiramate (Topamax); Medication Dosing Schedule: Days 1-3 50 mg q PM Days 4-7 50 mg BID Days 8-11 50 mg q AM & 100 mg q PM Days 12-15 100mg BID Days 16-19 100 mg q AM & 150 mg q PM Days 20-23 150 mg BID Days 24-27 150 mg qAM & 200 mg q PM Days 28-70 200 mg BID Days 71-77 150 mg BID Days 78-84 100mg BID Days 85-87 50 mg BID Days 88-91 50 mg qPM

Outcome Measures

Primary Outcome Measures

1. The Primary Outcome Measure Will be Subjects Ethanol Consumption Over the Course of the Drug Treatment Period as Assessed by the Timeline Followback Method [70 days]

   The primary outcome was the mean daily consumption of standard alcoholic drinks (14 g per ethanol) during the baseline week compared to week 10, the final week subjects were one maintenance dose of topirmate.

Secondary Outcome Measures

1. Phonetic Portion of the Controlled Word Association Test (COWAT) [Baseline compared to Week 10]

   Phonetic COWAT is a measure of verbal fluency. Results are in terms of number of words produced starting with a set of particular letters.This involves a comparison of baseline and Week 10 COWAT scores

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. DSM-IV Diagnosis of Alcohol Dependence; Minimal drinking level of 14 drinks per week for women and 20 drinks per week for men over a consecutive 30 day period during the last 90 days

2. Intent to stop drinking

3. Male or female age 18-65

4. Able to maintain sobriety for 3 consecutive days without the use of detoxification medications

5. Able to provide informed consent and to comprehend study procedures.

6. If a woman, then is willing to use an effective means of birth control during throughout the study period. These include: a. barrier (diaphragm or condom) with spermicide b.intrauterine progesterone contraceptive system c. levonorgestrel implant

1. medroxyprogesterone acetate contraceptive injection e. complete abstinence

Exclusion Criteria:

1. Dependent on or extensive abuse of drugs or substances other than ethanol, nicotine, or caffeine as assessed by urine toxicology (2 out of 3 Dependent on or extensive abuse of drugs or substances other than positive consecutive urines)

2. DSM IV Axis I diagnoses other than ethanol, caffeine, or nicotine dependence severe enough to require treatment with medication or to prevent compliance with the protocol.

3. Currently being treated with disulfiram (Antabuse), naltrexone (ReVia), or acamprosate

4. Currently being treated with any other psychoactive or other CNS medications or a carbonic anhydrase inhibitor (e.g. acetazolamide)

5. In need of medical detoxification from alcohol.

6. Prior history of kidney stones.

7. History of liver disease. ALT or AST 3 times higher than upper range of normal values.

8. BUN or serum creatinine outside the normal range

9. Major neurological disorder including seizures

10. Other major diseases including severe hypertension, renal disease, or cardiac disease.

11. Prior participation within 60 days in another clinical study.

12. If female, a positive serum HCG or breast feeding.

13. If female using oral contraceptives as a means of birth control.

14. History of allergic sensitivity to topiramate

15. Pending imprisonment

16. Cardiac pacemaker or metal surgical implant.

17. History of angle closure glaucoma.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston University Dept of Psychiatry Clinical Studies Unit	Boston	Massachusetts	United States	02118

Sponsors and Collaborators

• Boston University
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Ofra Sarid-Segal, MD, Boston University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00329407
• Other Study ID Numbers: H-22296
• First Posted: May 24, 2006
• Last Update Posted: Sep 8, 2010
• Last Verified: Aug 1, 2010

• Keywords provided by , ,: Alcoholism; Heavy Drinking; Alcohol Dependence
• Additional relevant MeSH terms: Alcoholism; Topiramate

Study Results

Participant Flow

Arm/Group Title	Topiramate Treatment
Arm/Group Description	In this open label non-placebo controlled trial all subjects received topiramate, the active medication.
Period Title: Overall Study
STARTED	10
COMPLETED	9
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Topiramate Treatment
Arm/Group Description	In this open label non-placebo controlled trial all subjects received topiramate, the active medication.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.7 (8.9)
Sex: Female, Male (Count of Participants)
Female	3 30%
Male	7 70%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	The Primary Outcome Measure Will be Subjects Ethanol Consumption Over the Course of the Drug Treatment Period as Assessed by the Timeline Followback Method
Description	The primary outcome was the mean daily consumption of standard alcoholic drinks (14 g per ethanol) during the baseline week compared to week 10, the final week subjects were one maintenance dose of topirmate.
Time Frame	70 days

Outcome Measure Data

Analysis Population Description

An ITT approach was used in the analysis. Least squares value for the baseline and 10 week of treatment were compared using a t test with Dunnett-Hsu adjustment. Differences between these means are presented as the result.

Arm/Group Title	Topiramate Treatment
Arm/Group Description	In this open label non-placebo controlled trial all subjects received topiramate, the active medication.
Measure Participants	10
Mean (Standard Error) [Standard Drink (14 g alcohol)]	-4.9 (0.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topiramate Treatment
	Comments	This was a within subject analysis. The null hypothesis was that there would be no significant difference in least squares means values obtained for the baseline and week 10 assessment weeks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	The Dunnett-Hsu adjustment was used to correct for multiple comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.7
	Confidence Interval	(2-Sided) 95%; -6.58 to -3.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.8
	Estimation Comments

2. Secondary Outcome

Title	Phonetic Portion of the Controlled Word Association Test (COWAT)
Description	Phonetic COWAT is a measure of verbal fluency. Results are in terms of number of words produced starting with a set of particular letters.This involves a comparison of baseline and Week 10 COWAT scores
Time Frame	Baseline compared to Week 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topiramate Treatment
Arm/Group Description	In this open label non-placebo controlled trial all subjects received topiramate, the active medication.
Measure Participants	10
Mean (Standard Error) [Number of words]	-11 (2.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topiramate Treatment
	Comments	This is a within subject comparison of COWAT scores botained for the baseline session and the Week 10 session. The null hypothesis is that there would be no difference between these scores.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	There would a significant reduction in COWAT scores between baseline and Week 10.
	Method	Mixed Models Analysis
	Comments	The Dunnett-Hsu adjustment was used to correct for multiple comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-11
	Confidence Interval	(1-Sided) 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.7
	Estimation Comments

Adverse Events

Arm/Group Title	Topiramate Treatment
Arm/Group Description	In this open label non-placebo controlled trial all subjects received topiramate, the active medication.
All Cause Mortality
	Topiramate Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Topiramate Treatment
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Topiramate Treatment
	Affected / at Risk (%)	# Events
Total	2/10 (20%)
Nervous system disorders
Agitation and Impaired Concentration	2/10 (20%)	2

Limitations/Caveats

Limitation of this trial include the small number of subjects included and lack of blinding, and inculsion of a placebo control group. An other limitation was the testing the active medication topiramate at om=nly one dose level (i.e. 400 mg daily).

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.