Cocaine DependencePhase 1/2NCT01137890
Effect of Zonisamide on Cocaine Reinforcement, Craving, and Relapse
A Phase 1/2 study testing Zonisamide, Cocaine Hydrochloride and Neurocognitive and Performance Battery in people with Cocaine Dependence, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 45 years
- Conditions the study is for
- Cocaine Dependence
- What is being tested?
- Zonisamide, Cocaine Hydrochloride and Neurocognitive and Performance Battery
- Type of treatment
- Pill or oral medicine, Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Aug 2013
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Behavioral Pharmacology Research Unit
Baltimore, Maryland, 21224
About this study
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.
Read the detailed description
This is a residential pilot trial to evaluate the effect of zonisamide (ZNS) on cocaine reinforcement, craving and relapse. Cocaine addiction remains a major social and medical problem that imposes a significant burden on our society, as more than a half million cocaine dependent individuals are seeking treatment every year. Medications that act to antagonize the glutamate system and/or increase the GABA-system are new targets in the search towards effective cocaine treatment. ZNS is part of a new line of antiepileptic agents that act both as glutamate antagonists and to enhance the Gamma-AminoButyric acid (GABA) system. Topiramate, a similar agent, showed a positive signal in a pilot trial for cocaine dependence. ZNS has the advantages of a longer half-life requiring only once a day dosing and, being better tolerated, it requires a shorter induction phase and can be administered at higher doses. We hypothesize that ZNS in moderate to high doses will attenuate the central effect of cocaine and improve the neural perturbations resulting from cocaine use, thus decreasing cocaine craving. Healthy, adult cocaine dependent volunteers will be enrolled on our residential unit for 44 days for this double-blind within subject study. The pharmacodynamic interactions between ZNS and cocaine will be measured in cocaine self-administration procedure offering alternative reinforcers with monetary values. Cocaine reinforcing effect will be evaluated over a range of doses, and subjective and objective outcomes on mood and behavior will be collected. In addition, the effect of ZNS on ad-lib smoking will be studied on the days when no other procedure interferes with smoking behaviors. Neurocognitive and psychomotor effects of ZNS treatment will also be studied with an extensive test battery on the day of the week when no cocaine is administered. This study will explore the potential therapeutic effect of ZNS for the treatment of cocaine dependence while providing necessary safety assessments required for possible future outpatient clinical trials.
- Conditions
- Cocaine Dependence
- Being tested
- Zonisamide, Placebo, Cocaine Hydrochloride, Neurocognitive and Performance Battery, Smoking Assessments
- Keywords
- cocaine, addiction, drug dependence, anticonvulsant, zonisamide, drug self-administration, nicotine withdrawal, neurocognition
- Medical subject headings
- Cocaine-Related Disorders, Behavior, Addictive, Substance-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZonisamideDrug
Also called Zonegran,, CAS 68291-97-4,
Eight capsules administered daily in split doses at 22:00 and 09:00.
PlaceboDrug
capsules administered in split doses at 22:00 and 09:00.
Cocaine HydrochlorideDrug
Also called CAS 50-36-2, methylbenzoylecgonine, benzoylmethylecgonine, C17H21NO4
Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring.
Neurocognitive and Performance BatteryBehavioural
Participants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment.
Smoking AssessmentsBehavioural
Participants answer questions about smoking and smoking behaviors are monitored.
| Study group | Role | What they receive |
|---|---|---|
| Zonisamide | Experimental | Participants administered blind capsules containing either placebo or zonisamide. Receives: Drug: Zonisamide; Drug: Cocaine Hydrochloride; Behavioral: Neurocognitive and Performance Battery; Behavioral: Smoking Assessments |
| Placebo | Placebo comparator | Participants administered only placebo capsules containing lactose. Receives: Drug: Placebo; Drug: Cocaine Hydrochloride; Behavioral: Neurocognitive and Performance Battery; Behavioral: Smoking Assessments |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: Day 1-39
Secondary outcomes (1)
Drug Value Questionnaire
Street Value of Sampled Dose. After co-administration of cocaine-zonisamide, participants were asked to hypothetically estimate the value of the drug they received, if they were to purchase it on the street. The mean value (dollars) across all drug conditions is reported here.
Repeated within-subject measures ANOVA performed to observe the main effects of zonisamide dose (0, 300, and 600mg) and cocaine dose (0, 20, and 40mg), and their interaction. Only participants who received the active zonisamide medication (n=8) were included in this portion of the analysis. Additionally, all 8 subjects who received zonisamide completed both 300mg and 600mg doses.
Within-subject repeated interval during self-administration sessions. Cocaine not administered (only Zon) during Weeks 2 \& 4, thus no measures taken at these times
Measured: Weeks 1-5; mean of weeks 1, 3 and 5 reported
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2010 (estimated)
- Study startJun 2010
- Primary completionMar 2012
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cocaine DependenceStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Annie Umbricht, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01137890
- Sponsor's protocol ID
- R01DA027065
- Other IDs
- R01DA027065
- Status last verified
- Sep 2017
- First submitted
- 3 Jun 2010
- Last updated
- 5 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Zonisamide on Cocaine Reinforcement, Craving, and Relapse
- ClinicalTrials.gov ID
- NCT01137890
- Acronym / sponsor ID
- R01DA027065
- Conditions
- Cocaine Dependence
- Keywords
- cocaine, addiction, drug dependence, anticonvulsant, zonisamide, drug self-administration, nicotine withdrawal, neurocognition
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Jun 2010
- Primary completion
- Mar 2012 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 7 Jun 2010 (estimated)
- Results
- Posted 5 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a residential pilot trial to evaluate the effect of zonisamide (ZNS) on cocaine reinforcement, craving and relapse. Cocaine addiction remains a major social and medical problem that imposes a significant burden on our society, as more than a half million cocaine dependent individuals are seeking treatment every year. Medications that act to antagonize the glutamate system and/or increase the GABA-system are new targets in the search towards effective cocaine treatment. ZNS is part of a new line of antiepileptic agents that act both as glutamate antagonists and to enhance the Gamma-AminoButyric acid (GABA) system. Topiramate, a similar agent, showed a positive signal in a pilot trial for cocaine dependence. ZNS has the advantages of a longer half-life requiring only once a day dosing and, being better tolerated, it requires a shorter induction phase and can be administered at higher doses. We hypothesize that ZNS in moderate to high doses will attenuate the central effect of cocaine and improve the neural perturbations resulting from cocaine use, thus decreasing cocaine craving. Healthy, adult cocaine dependent volunteers will be enrolled on our residential unit for 44 days for this double-blind within subject study. The pharmacodynamic interactions between ZNS and cocaine will be measured in cocaine self-administration procedure offering alternative reinforcers with monetary values. Cocaine reinforcing effect will be evaluated over a range of doses, and subjective and objective outcomes on mood and behavior will be collected. In addition, the effect of ZNS on ad-lib smoking will be studied on the days when no other procedure interferes with smoking behaviors. Neurocognitive and psychomotor effects of ZNS treatment will also be studied with an extensive test battery on the day of the week when no cocaine is administered. This study will explore the potential therapeutic effect of ZNS for the treatment of cocaine dependence while providing necessary safety assessments required for possible future outpatient clinical trials.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zonisamide | Experimental | Drug: Zonisamide, Drug: Cocaine Hydrochloride, Behavioral: Neurocognitive and Performance Battery, Behavioral: Smoking AssessmentsParticipants administered blind capsules containing either placebo or zonisamide. |
| Placebo | Placebo comparator | Drug: Placebo, Drug: Cocaine Hydrochloride, Behavioral: Neurocognitive and Performance Battery, Behavioral: Smoking AssessmentsParticipants administered only placebo capsules containing lactose. |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (13 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZonisamideAlso: Zonegran,, CAS 68291-97-4,Eight capsules administered daily in split doses at 22:00 and 09:00. | Drug | Zonisamide |
| Placebocapsules administered in split doses at 22:00 and 09:00. | Drug | Placebo |
| Cocaine HydrochlorideAlso: CAS 50-36-2, methylbenzoylecgonine, benzoylmethylecgonine, C17H21NO4Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring. | Drug | Placebo, Zonisamide |
| Neurocognitive and Performance BatteryParticipants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment. | Behavioural | Placebo, Zonisamide |
| Smoking AssessmentsParticipants answer questions about smoking and smoking behaviors are monitored. | Behavioural | Placebo, Zonisamide |
Primary outcome
Change in Visual Analog Questionnaire (VAQ) Score
Time frame: Weeks 1-5; mean of weeks 1, 3 and 5 reported
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
Behavioral Choice Measures
Time frame: Weeks 1-5, mean of weeks 1, 3 and 5 reported
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
Cocaine Craving
Time frame: Day 1-39
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.
1 secondary outcome
Drug Value Questionnaire
Time frame: Weeks 1-5; mean of weeks 1, 3 and 5 reported
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Cocaine Dependence
Recruiting
rTMS and Cognitive-behavioral Therapy for Cocaine Use Disorder
Cocaine Use, Cocaine Dependence
Not yet recruiting
QAIAx - SGI/SI Smart Health Cities: Microcity Enclave Program (Quantum SI/AGI Agency a/k/a AI City Hall Project - UPSTO App Nos. 64/074,526, 64/063,557, 64/105,164, 63/903,181, 63/729,428, 64/125,360; USPTO EO 9424 Assignment ID: 2101042 / ARN: REEL/FRAME: 76481/0026 - OUSD-R&E, Department of War)
Asperger's Disorder, Asperger Disorder
Recruiting
Transcranial Direct Current Stimulation (tDCS) for Treatment of Substance Use Disorder
Cocaine Use Disorder, Cocaine Dependence
RecruitingPhase 1
Safety Study of a Disrupted Adenovirus (Ad) Serotype Cocaine Vaccine for Cocaine-dependent Individuals
Cocaine Dependence
Active, not recruitingPhase 1
AAV8-hCocH for Cocaine Use Disorder
Cocaine Dependence, in Remission
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annie Umbricht, M.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Zonisamide, Cocaine Hydrochloride and Neurocognitive and Performance Battery in people with Cocaine Dependence, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Visual Analog Questionnaire (VAQ) Score (time frame: Weeks 1-5; mean of weeks 1, 3 and 5 reported). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2017; AzTrials last refreshed its copy on 8 Nov 2026.