Alcohol Self Administration Laboratory

• Sponsor: Boston University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00398918
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a pilot study in which our intent is to establish an alcohol administration laboratory in which we will be able to test the effect of the anticonvulsant medication zonisamide as compared to placebo on alcohol self administration and on cognitive functioning in non treatment seeking heavy users of alcohol. Our first goal is to establish the safety of zonisamide when used together with alcohol. Our second goal is to test the effect of an acute dose of zonisamide on alcohol consumption and show that it may reduce the consumption of alcohol. To achieve this goal we seek subjects with a history of heavy drinking to be tested on the self-administration procedures described below in two sessions with either zonisamide or placebo. These procedures will involve first, the administration of a challenge dose of ethanol to evaluate the effect of alcohol on performance on neuropsychological tests. This initial challenge will be followed by a period of alcohol self-administration in which the research subject can choose to select either ethanol or another reinforcer, money.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism	Drug: zonisamide; Drug: Placebo	N/A

Detailed Description

In preclinical studies three novel anticonvulsants have been studied. The administration of tiagabine did not decrease ethanol consumption in rodents (Schmitt et al., 2002; Rimondini et al., 2002). In a study with alcohol preferring mice topiramate reduced alcohol consumption in a two bottle choice prolonged access model of drinking (Gabriel and Cunningham, 2005). In a study done at our laboratory both topiramate and zonisamide were found to have similar effects on reducing the consumption of ethanol in Wistar rat (Knapp et al., 2004). More recently we found that zonisamide administration decreased alcohol consumption in a limited access model in the C57BL/B6 mouse. These results suggest that zonisamide might be useful as a medication for the treatment of alcohol dependence.

Topiramate and zonisamide have some structural similarities with a sulfamate or methane-sulfonamide containing chain respectively attached to cyclic structure. These structural similarities may explain some of their pharmacological similarities including blockade of voltage sensitive sodium channels and low potency inhibition of carbonic anhydrase (Taverna et al., 1999; Dodgson et al., 2000; Schaf et al., 1987; Masudaet al., 1993). Both topiramate and zonisamide promote weight loss (McElroy et al., 2003; McElroy et al., 2004; Gadde et al., 2003). This effect may be a result of neuromodulation of the regulation of alcohol and food shared by these drugs.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Alcohol Self Administration Laboratory
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Oct 1, 2007
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zonisamide	Drug: zonisamide; zonisamide (100 mg)one time; Other Names: zonegran
Placebo Comparator: Placebo	Drug: Placebo; Placebo Comparator

Outcome Measures

Primary Outcome Measures

1. Grams Ethanol Consumed During Second Hour of the Alcohol Self-Administration Sessions [1 day]

   Grams Ethanol Consumed During Second Hour of the Alcohol Self-Administration Sessions for Zonisamide and Placebo Conditions

Secondary Outcome Measures

1. Score Digit Symbol Modalities Test [40 minutes post alcohol ingestion]

   Difference score between zonisamide and placebo treatment conditions for the Digit Symbol Modalities Test scores obtained 40 minutes after ingestion of a priming dose of ethanol.This test involves transcribing from a key in which numbers appear below a series of symbols to boxes below symbols matched to those in the key. This task must be completed in 90 nseconds. This test measures visuomotor speed and aspects of attention. Scoring is the total number of correctly transcribed numbers. The maximum score on this test 110 points.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Non treatment seeking subjects ages 21-55 must indicate no treatment for alcohol dependence in the preceding 6 months.

2. Male subjects must drink no more than 40 standard drinks; female subjects no more than 35 standard drinks a week as determined by the TLFB

3. Subjects must be able to provide IC

4. BAC must be 0.000 at the time of consent

5. Female subjects of a child bearing potential must use an acceptable method of contraception which includes a barrier and spermicide, levonorgestrel implant, medroxyprogesterone, intrauterine progesterone contraceptive system or complete abstinence or surgical sterilization. Women who are using oral contraceptives must agree to an additional barrier method.

Exclusion Criteria:

1. Subject meeting DSM-IV-TR criteria for axis I diagnosis that require pharmacological treatment.

2. Subject meeting substance dependence criteria for any substance other than alcohol or nicotine .

3. Positive urine toxicology screen for opioids, cocaine, amphetamines, PCP, THC (may repeat THC if positive).

4. History of severe alcohol withdrawals.

5. Any medical or psychological condition that in the opinion of the investigator will preclude safe participation in the trial. These include a history of kidney stones in the past 10 years, significant liver disease with AST and ALT more than 3 times the normal range.

6. Concomitant medications that will alter the pharmacodynamic/pharmacokinetic properties of the study medication. Participant who are taking the following medications: Amprenavir; Atazanavir; Clarithromycin; Delavirdine; Diclofenac; Fosamprenavir; Imatinib; Indinavir; Isoniazid; Itraconazole; Ketoconazole; Miconazole; Nefazodone; Nelfinavir; NiCARdipine; Propofol; Quinidine; Ritonavir; Telithromycin; Phenytoin; carbamazepine and phenobarbital

7. Subjects on psychoactive medications must be on a stable dose more than 3 months

8. Female subjects who are pregnant or nursing.

9. Subject is facing future imprisonment.

10. A known allergy to zonisamide or sulfa.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston University Medical Campus	Boston	Massachusetts	United States	02118

Sponsors and Collaborators

• Boston University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Boston University
• ClinicalTrials.gov Identifier: NCT00398918
• Other Study ID Numbers: H-25360
• First Posted: Nov 14, 2006
• Last Update Posted: Jul 14, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Alcoholism; Zonisamide

Study Results

Participant Flow

Arm/Group Title	Zonisamide-Placebo Sessions
Arm/Group Description	In this within subjects study, subjects received zonisamide in one session and placebo in a second
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Zonisamide-Placebo Sessions
Arm/Group Description	In this within subjects study, subjects received zonisamide in one session and placebo in a second
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	7 70%
Male	3 30%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Grams Ethanol Consumed During Second Hour of the Alcohol Self-Administration Sessions
Description	Grams Ethanol Consumed During Second Hour of the Alcohol Self-Administration Sessions for Zonisamide and Placebo Conditions
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

This was a laboratory based study. An ITT analysis was used.

Arm/Group Title	Zonisamide-Placebo Sessions
Arm/Group Description	In this within subjects study, subjects received zonisamide in one session and placebo in a second
Measure Participants	10
Zonisamide	9.0 (3.7)
Placebo	18.2 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zonisamide-Placebo Sessions
	Comments	The analysis involved a within subjects comparison. The null hypothesis was that there would be no difference in the amount of ethanol consumed in either the first or second hour of self-administration sessions. Results presented here are for the second hour of the self-administration sessions.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Mixed Models Analysis
	Comments	Results presented are for post-hoc comparisons of least squares means with Tukey-Kramer adjucted p values.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.2
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.4
	Estimation Comments	The estimated value is for the difference between the means obtained for the second hour of the self-administration sessions for the placebo and zonisamide conditions.

2. Secondary Outcome

Title	Score Digit Symbol Modalities Test
Description	Difference score between zonisamide and placebo treatment conditions for the Digit Symbol Modalities Test scores obtained 40 minutes after ingestion of a priming dose of ethanol.This test involves transcribing from a key in which numbers appear below a series of symbols to boxes below symbols matched to those in the key. This task must be completed in 90 nseconds. This test measures visuomotor speed and aspects of attention. Scoring is the total number of correctly transcribed numbers. The maximum score on this test 110 points.
Time Frame	40 minutes post alcohol ingestion

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Zonisamide-Placebo Sessions
Arm/Group Description	In this within subjects study, subjects received zonisamide in one session and placebo in a second
Measure Participants	10
Mean (Standard Error) [Numeric Score]	2.2 (5.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zonisamide-Placebo Sessions
	Comments	Null hypothesis: No difference in DSMT scores for zonisamide and placebo treatments 40 minutes after ingestion of ethanol.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments	P value shown is for a post-hoc comparison of least squares means generated by the mixed model used.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.2
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.7
	Estimation Comments	Analysis for difference between DSMT scores at 40 minutes post alcohol ingestion for zonisamide and placebo involved post-hoc comparisons of least squares means.

Adverse Events

Arm/Group Title	Zonisamide-Placebo Sessions
Arm/Group Description	In this within subjects study, subjects received zonisamide in one session and placebo in a second
All Cause Mortality
	Zonisamide-Placebo Sessions
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Zonisamide-Placebo Sessions
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Zonisamide-Placebo Sessions
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

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.