Alcohol Self Administration Laboratory

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.

Study Overview

• Status: Completed
• Conditions: Alcoholism
• Intervention / Treatment: Drug: Placebo; Drug: zonisamide

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score Digit Symbol Modalities Test	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.	40 minutes post alcohol ingestion

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: November 13, 2006
• First Submitted That Met QC Criteria: November 13, 2006
• First Posted (Estimate): November 14, 2006

Study Record Updates

• Last Update Posted (Actual): July 14, 2017
• Last Update Submitted That Met QC Criteria: June 17, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Zonisamide
• Other Study ID Numbers: H-25360

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No