Early Phase II Trials for Cocaine Medication Development - 1

Early Phase II Trials for Cocaine Medication Development

The purpose of this study is to develop models for early Phase II testing of potential medications for cocaine dependence: amoxapine, risperidone and other agents.

The study was a controlled pilot trial of risperidone in opiate-dependent patients on methadone maintenance. The study explored whether risperidone reduced cocaine use, cocaine craving, and cocaine subjective effects in patients on methadone maintenance who abused cocaine and whether it had an acceptable side effect profile. This

Study Overview

• Status: Completed
• Conditions: Substance-Related Disorders; Cocaine-Related Disorders
• Intervention / Treatment: Drug: Placebo; Behavioral: Relapse prevention counseling; Drug: Risperidone

Detailed Description

This was an 18-week prospective, randomized, placebo-controlled crossover design with placebo lead-in phase and terminal placebo phase. After two weeks of single-blind placebo, patients were randomly assigned to one of two schedules of medication:

2 Week Baseline Weeks 1-6 Weeks 7-12 Weeks 13-18 Group 1 placebo risperidone placebo placebo Group 2 placebo placebo risperidone placebo

The first 6-week phase provided an initial double-blind medication-placebo comparison. In the second six-week phase (weeks 7-12), patients crossed over to the opposite treatment. During weeks 13-18, Group 1 patients remained on placebo while Group 2 patients were tapered from risperidone to placebo. For six weeks after the end of the trial, patients were offered routine clinical treatment with counseling and psychiatrist visits as needed. Medication dosage was titrated upwards on a fixed-flexible schedule to a maximum dose of 4 mg per day. Medication began at ½ mg risperidone for 3 days, then 1 mg for four days, 2 mg per day during week 2, 3 mg per day during week 3, and 4 mg per day during weeks 4-6. The titration schedule for risperidone in weeks 7-12 was the same as for weeks 1-6. In addition to treatment as usual, patients received a modified manual-guided relapse prevention counseling program in weekly meetings lasting approximately 20 minutes; these sessions provided cognitive and behavioral skills that were found to be helpful to patients in reducing cocaine use.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • NYS Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion:

1. good standing at methadone maintenance program
2. DSM-IV criteria for cocaine dependence or abuse
3. used cocaine at least 4 times in last month
4. able to give informed consent

Exclusion criteria

1. currently meets DSM-IV criteria for Major depression or dysthymia
2. meets DSM-IV criteria for attention deficit hyperactivity disorder, bipolar disorder, schizophrenia or any psychotic disorder
3. history of seizures
4. history of allergic reaction to risperidone
5. chronic organic mental disorder
6. significant current suicidal risk
7. pregnancy, lactation or failure to use adequate birth control (for females)
8. unstable physical disorders that may make participation hazardous
9. coronary vascular disease
10. cardiac conduction system disease as indicated by QRS duration >/= 0.11
11. current use of other prescribed psychotropic medications
12. history of failure to respond to a previous adequate trial of risperidone
13. history of neuroleptic malignant syndrome, tardive dyskinesia, or severe extrapyramidal reactions to neuroleptic medications
14. current DSM-IV criteria for another substance dependence other than nicotine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: PLacebo; Placebo plus relapse prevention counseling	Drug: Placebo; Placebo; Behavioral: Relapse prevention counseling; Modified manual guided relapse prevention counseling. Weekly 20 minute sessions consisting of cognitive behavioral skills. Both arms will receive this intervention.; Other Names: RPT-CBT
Experimental: Risperidone; Risperidone (4mg/day) plus relapse prevention counseling	Behavioral: Relapse prevention counseling; Modified manual guided relapse prevention counseling. Weekly 20 minute sessions consisting of cognitive behavioral skills. Both arms will receive this intervention.; Other Names: RPT-CBT; Drug: Risperidone; Risperidone (4mg/day); Other Names: Risperidal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects	Using the Modified Systemic Assessment for Treatment Emergent Effects the psychiatrist assessed side effects	1x/week for 18 weeks
Craving	subjective cravings were recorded on the Cocaine craving scale	3x/week during 18 weeks of trial
Drug use	urine drug testing and self reported use on the Substance Use Weekly Inventory	3x/week during 18 weeks of trial
Retention	duration of individuals in the study.	18 weeks or length of study participation

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute on Drug Abuse (NIDA); Research Foundation for Mental Hygiene, Inc.
• Investigators: Principal Investigator: Edward Nunes, M.D., NYS Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 1996
• Primary Completion (Actual): July 1, 1999
• Study Completion (Actual): July 1, 1999

Study Registration Dates

• First Submitted: September 20, 1999
• First Submitted That Met QC Criteria: September 20, 1999
• First Posted (Estimate): September 21, 1999

Study Record Updates

• Last Update Posted (Actual): June 26, 2017
• Last Update Submitted That Met QC Criteria: June 22, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Cocaine; METHADONE PATIENTS; RISPERIDONE
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Cocaine-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: #3124; R01DA009582 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

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