Effect of Zonisamide on Cocaine Reinforcement, Craving, and Relapse

NCT01137890 | Completed Phase 1 Results

• 1 other identifier: R01DA027065
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This is a residential pilot trial to evaluate the pharmacodynamic interaction between zonisamide and cocaine, with the goal of evaluating zonisamide's potential for the treatment of cocaine dependence.

Conditions

Cocaine Dependence

Keywords

cocaine; addiction; drug dependence; anticonvulsant; zonisamide; drug self-administration; nicotine withdrawal; neurocognition

Outcome Measures

Primary Outcomes (3)

• Change in Visual Analog Questionnaire (VAQ) Score

  VAQ measures the change in effect after dose administration. Participants rate 6 items ("Any Drug Effect", "Rush", "Good Effects", "Bad Effects", "Liking", \& "Desire for Cocaine") by pointing an arrow along a 100-point line anchored at either end with "none" (0) \& "extremely" (100). Each participant's score is equal to the sum of all 6 ratings, \& the mean of all participant's scores is reported across each condition. The VAQ is only administered to subjects in the zonisamide (Zon) condition (n=8). Repeated within-subject measures ANOVA performed to observe the main effects of Zon dose (0, 300, \& 600mg) \& cocaine dose (1, 20, \& 40mg), \& their interaction. All 8 subjects who received Zon completed both 300mg \& 600mg doses. Assessments obtained on Week 1 (0mg Zon), Week 3 (300mg Zon), \& Week 5 (600mg Zon), in which all 3 cocaine were co-administered at these times. Cocaine not administered (only Zon) during Weeks 2 \& 4, thus no measures taken at these times

  Weeks 1-5; mean of weeks 1, 3 and 5 reported

• Behavioral Choice Measures

  In each condition of cocaine-zonisamide dose, participants were asked to choose whether they would rather have a repeated cocaine dose (same dose as most recent administration) or cash of varying monetary value. The mean number of cocaine choices across each drug condition are reported. This measure only included participants in the zonisamide (Zon) condition (n=8), with each arm representing variation in co-administration of cocaine-Zon. Repeated within-subject measures ANOVA performed to observe the main effects of zonisamide dose (0, 300, and 600mg) and cocaine dose (1, 20, and 40mg), and their interaction. Only participants who received the active zonisamide medication (n=8) were included in this portion of the analysis. During self-administration sessions are every 15 min over 1hr45min period. Assessment on Weeks 1 (0mg Zon), 3 (300mg Zon), 5 (600mg Zon), in which varying cocaine doses co-administered. Cocaine not administered (only Zon) during Weeks 2 \& 4

  Weeks 1-5, mean of weeks 1, 3 and 5 reported

• Cocaine Craving

  Cocaine craving measured by Cocaine Selectivity Severity Assessment (CSSA). The CSSA is a reliable and valid tool to measure cocaine withdrawal severity within a 24 hr period, and has been shown to predict treatment response in a treatment setting. Participants are asked to rate 18-items on a Likert scale 0-7, with composite scores ranging 0-126 and higher numbers indicative of more severe withdrawal. Mean scores on CSSA across 39-day time period are reported.

  Day 1-39

Secondary Outcomes (1)

• Drug Value Questionnaire

  Weeks 1-5; mean of weeks 1, 3 and 5 reported

Study Arms (2)

Zonisamide

EXPERIMENTAL

Participants administered blind capsules containing either placebo or zonisamide.

Drug: Zonisamide; Drug: Cocaine Hydrochloride; Behavioral: Neurocognitive and Performance Battery; Behavioral: Smoking Assessments

Placebo

PLACEBO COMPARATOR

Participants administered only placebo capsules containing lactose.

Drug: Placebo; Drug: Cocaine Hydrochloride; Behavioral: Neurocognitive and Performance Battery; Behavioral: Smoking Assessments

Interventions

Zonisamide DRUG

Eight capsules administered daily in split doses at 22:00 and 09:00.

Also known as: Zonegran,, CAS 68291-97-4,

Zonisamide

Placebo DRUG

capsules administered in split doses at 22:00 and 09:00.

Placebo

Cocaine Hydrochloride DRUG

Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring.

Also known as: CAS 50-36-2, methylbenzoylecgonine, benzoylmethylecgonine, C17H21NO4

Placebo; Zonisamide

Neurocognitive and Performance Battery BEHAVIORAL

Participants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment.

Placebo; Zonisamide

Smoking Assessments BEHAVIORAL

Participants answer questions about smoking and smoking behaviors are monitored.

Placebo; Zonisamide

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age at least 21 years old, not older than 45 years.
• Evidence of cocaine dependence.
• Not seeking treatment for cocaine abuse.
• Able and willing to be restricted to our unit for 6-7 weeks.
• Able to answer frequent questionnaires reliably and consistently.
• Smoker.

You may not qualify if:

• Allergy to Sulfonamide drugs (e.g. topiramate, zonisamide, sulfamethoxazole/trimethoprim).
• Diabetes, respiratory insufficiency, renal tubular acidosis or renal insufficiency, heart failure, liver insufficiency, chronic diarrhea, other chronic diseases predisposing to acidosis.
• Renal insufficiency defined as serum creatine \> 1.30 mg/DL for males or \> 1.03 mg/DL for females.
• History of nephrolithiasis, unexplained hematuria on screening urinalysis.
• History of head injury (with loss of consciousness longer than a few minutes).
• History of seizure, or use of antiepileptic medications.
• HIV positive individuals who meet AIDS by Centers for Disease Control (CDC) criteria or are on antiretroviral medications.
• BMI \< 19 or BMI \> 34.
• Total cholesterol \> 240mg%.
• Serous psychiatric illness with psychosis, dementia.
• Glaucoma, family history of glaucoma, one-sided blindness.
• For female participants: being pregnant, lactating or not using an effective method of contraception.
• Physical dependence on any drug other than cocaine, nicotine, or caffeine.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Behavioral Pharmacology Research Unit

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders; Behavior, Addictive; Substance-Related Disorders

Interventions

Zonisamide; Cocaine

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders; Compulsive Behavior; Impulsive Behavior; Behavior

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Dr. Annie Umbricht
• Organization: Johns Hopkins University

annieumbricht@jhu.edu

410-550-1917

Study Officials

• Annie Umbricht, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2010
• First Posted: June 7, 2010
• Study Start: June 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: August 1, 2013
• Last Updated: September 5, 2017
• Results First Posted: September 5, 2017

Record last verified: 2017-09

Locations

US (1)