Efficacy of Levetiracetam in Cocaine-Abusing Methadone Maintained Patients (Keppra-DB)

January 12, 2018 updated by: Yale University

Levetiracetam (Keppra) Treatment for Cocaine Dependence in Methadone-Maintained Patients

Concurrent dependence on cocaine occurs in up to 50% of the over one million opiate dependent patients in spite of methadone maintenance treatment being highly effective for opiate dependence and having excellent treatment retention. Cocaine dependence has remained largely unresponsive to medications both in and outside of these methadone programs. We have initial data from our open-label study with levetiracetam showing that this medication is well tolerated and may reduce cocaine use in this cocaine-abusing methadone treated population.

The specific aim of this study is to evaluate the efficacy of levetiracetam 3 grams/day in modifying cocaine-using behavior, reducing cocaine craving and attenuating cocaine's reinforcing effect among methadone-maintained patients. The primary outcomes will be reduction in cocaine use as assessed by self-report and thrice-weekly urinalyses. Secondary outcomes will include weeks in treatment (retention) and change in measures of cocaine craving, anxiety symptoms and opiate withdrawal symptoms.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This 17-week double-blind, placebo controlled randomized pilot clinical trial will provide treatment for 40 cocaine-dependent opioid dependent patients. Participants, aged 18-65 years, will be randomized to receive levetiracetam 3000 mg/day or placebo while concurrently receiving treatment with methadone. Baseline cocaine use will be determined during the first week of treatment participation. (Gossop et al., 1997) The study design will have three overlapping phases that are summarized below: 1) A one week methadone fixed induction (week 1) and flexible methadone stabilization phase (weeks 2-13); 2) an 12-week "treatment" phase (weeks 2-13), consisting of slow titration and stabilization on study medication; and 3) a four week "taper, detoxification or transfer" phase (weeks 13-17).

During the first week of induction onto methadone, participants will be administered increasing doses of methadone starting at 30 mg daily and increased up to 60 mg daily by the end of the first week. This methadone dose will be adjusted for stabilization of opiate withdrawal symptoms using a flexible dosing from 40 mg up to 150 mg between weeks 2 to 12. This range has been found to be adequate for the vast majority of patients receiving methadone in our program and is designed to accommodate participants who may not be able to tolerate the higher maintenance doses or may still experience withdrawal symptoms, respectively. We may increase or decrease this amount on a case-by-case basis based on physician assessment of self-reported and observed symptoms.

Starting on week 2 subjects will start study medication in one of two randomly assigned experimental groups: levetiracetam 3000 mg /day (active medication) or placebo (inactive medication). Concurrent with the stabilization on methadone, levetiracetam will be increased from 500mg/day on week 2 and this dose will be slowly titrated to a total of 3000mg/day or maximum tolerated dose (MTD). Subjects will remain on their full dosage through week 13.

At the end of week 13, participants will undergo detoxification from methadone over a 4-week period (weeks 13-17) and discontinuation from levetiracetam over a concurrent 2-week period.

All participants will receive weekly 1-hour of individual psychotherapy (Cognitive Behavioral Treatment) with experienced clinicians specifically trained to deliver the therapy and who will receive ongoing supervision. The primary outcomes will be reduction in cocaine use, as assessed by self-report and thrice-weekly urinalyses. Secondary outcomes will include weeks in treatment (retention), reported medication side effects (medication tolerability), and change in measures of: cocaine craving, anxiety symptoms and opiate withdrawal symptoms. This study will occur at the Outpatient Treatment Research Program in Building 36 at the VA CT Healthcare System.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
28

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • West Haven, Connecticut, United States, 06516
        • VA CT Healthcare System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Between the ages of 18-65 years.
  • Participants must demonstrate current opioid dependence as determined by study physician or APRN, self-reported history of opioid dependence for one year and a positive urine of opiates. Participants may be transferred from other methadone maintenance programs, including the WHVA methadone program.
  • Participants also must be current users of cocaine with self-reported use of cocaine > 1 time/week in at least one month preceding study entry, cocaine-positive urine screen and score over 3 as assessed with the Severity Dependence Scale.
  • Women of childbearing age are eligible to be included in the study if they have a negative pregnancy test at screening, agree to adequate contraception to prevent pregnancy, to have monthly pregnancy tests, and they understand the risk of fetal toxicity due to medication and cocaine.

Exclusion Criteria:

  • Current diagnosis of other drug or alcohol dependence (other than opiates, cocaine or tobacco).
  • Patients with serious medical illness (e.g., major cardiovascular, renal, endocrine, hepatic, and serious neurological disorders including any history of seizures).
  • Patients with current serious psychiatric illness or history of psychosis, schizophrenia, bipolar type I disorder and subjects with suicidal or homicidal thoughts or taking psychotropic medications.
  • Women who are pregnant, nursing or refuse to use a reliable form of birth control or refuse monthly testing.
  • Screening liver function tests (SGOT or SGPT) greater than 3 times normal and renal function test (creatinine) greater than 1.5 mg/dl.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 1
Levetiracetam tablets
Drug: levetiracetam
The participants will start receiving Levetiracetam 500mg in the mornings of the first day on week 2. The dose will be titrated every third day, until the target dose of 3000mg/day is achieved by week 4. The study medication must be titrated to 3000 mg/day or to the subject's maximum tolerated dose (MTD). The physician overseeing this titration as well as all study staff will be blind to the subject's medication administration. The medication will be discontinued over a two-week period.
Placebo Comparator: 2
matching placebo
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
Time Frame: Weekly from baseline to week 12
The primary outcome variable was the change from baseline to week 13 of the thrice weekly cocaine-free urine scores. In this repeated ordinal variable, 0 represented all 3 urine samples submitted by the subject as positives, 1 represented some urine samples submitted by the subject were negative, and 2 represented all 3 urine samples submitted by the subjects were negative for cocaine. Balancing the distribution between these categories improved the models for the analysis of repeated ordinal data. Data is summarized as number of participant that were cocaine free urine (score 2) per week by group.
Weekly from baseline to week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
Time Frame: Weekly from baseline to week 12
The secondary outcome variable was the change from baseline to week 13 of the thrice weekly opioid-free urine scores. In this repeated ordinal variable, 0 represented all 3 urines samples submitted by the subject as positives, 1 represented some urine samples submitted by the subject were negative, and 2 represented all 3 urines samples submitted by the subjects were negative for opioids excluding methadone. Balancing the distribution between these categories improved the models for the analysis of repeated ordinal data. Data summarized by number of participants who were had opioid free urine samples (score 2) per week by group.
Weekly from baseline to week 12
Treatment Retention
Time Frame: Week 13
Weekly from week 1 to 13
Week 13
Cocaine Craving
Time Frame: Weekly from baseline to week 12
Weekly cocaine craving was measure at intake and weekly after with the Visual Analog Scale (VAS) of the Cocaine Selective Severity Assessment. The VAS measures the intensity of cocaine craving with a scale from 0 (No desire at all) to 7 (Unable to resist), and frequency of cocaine craving in the previous 24 hours with a scale from 0 ( never) to 7 ( all the time). The scale is totaled for a maximum number of 14, the minimum is 0. (Kampman et al., 1998; Mulvaney et al., 1999).
Weekly from baseline to week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gerardo Gonzalez, MD, Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2008

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 17, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 19, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 17, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0707002832
  • 5R01DA017782-04 (U.S. NIH Grant/Contract)
  • NIDA-5R01DA017782-04
  • Yale-0508000534
  • VA-gg0006

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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