Pharmacotherapy & CM for Opioid and Cocaine Dependence

The purpose of this study is to compare the efficacy of the combined treatment modafinil + Contingency Management (CM) to either treatment condition alone or to yoked-controls on cocaine abstinence.

To investigate the role of modafinil-related improvements in memory, impulse control, and attention in mediating cocaine abstinence.

Study Overview

• Status: Completed
• Conditions: Cocaine Dependence
• Intervention / Treatment: Drug: Modafinil; Behavioral: Contingency Management; Drug: Methadone; Behavioral: cognitive behavioral treatment; Drug: Sugar Pill; Behavioral: Voucher Control

Detailed Description

We hypothesize that the treatment group receiving the combination of modafinil + Contingency Management will have significantly lower cocaine use than the other treatment conditions. We also hypothesize that improvements in memory, impulse control, and attention will be a significant contributor to the treatment improvements investigated in Specific Aim #1.

Opioid and cocaine dependence are major problems among veteran and non-veterans and no effective pharmacotherapy exists for cocaine dependence. Methadone has not shown robust effectiveness in reducing cocaine abuse. Thus, new treatments are needed for the individuals who have developed cocaine dependence. This study is designed to test a new pharmacotherapy for cocaine dependence and is a placebo-controlled trial.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Department of Veterans Affairs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female opioid-dependent patients between the ages of 18-65 will be entered into the study. Females must not be pregnant as determined by pregnancy screening, nor breast feeding, and must be using acceptable birth control methods during study participation.
• Current opioid dependence as evidenced by documentation of prior treatment for opioid dependence or signs of withdrawal, self-reported history of opioid dependence for consecutive 12 month period and a positive urine for opiates.
• Subjects must fulfill DSM-IV criteria for opioid and cocaine dependence.
• Subjects must have a history of cocaine use, with a reported street cocaine use of a minimum of 1/2 gram during the preceding 30 days. Additionally, laboratory confirmation of recent cocaine use (positive urine for cocaine) within 2 weeks prior to admission to the study is required.
• Subjects must be treatment-seekers for opioid and cocaine use.

Exclusion criteria:

• Current DSM-IV diagnosis of other drug or alcohol dependence (other than opiates, cocaine, or tobacco)
• History of heart disease, left ventricular hypertrophy, ischemic ECG changes, chest pain, arrhythmia, hypertension.
• History of severe renal, endocrine or hepatic diseases.
• History of psychosis, schizophrenia, or bipolar type I.
• History of seizure disorder.
• Current use of over-the-counter or prescription psychoactive drugs (antidepressant, anxiolytics, antipsychotics, mood stabilizers, psychostimulants).
• Liver function tests (SGOT,SGPT) greater than 3 times normal.
• Current use of modafinil
• Current suicidality
• Pregnancy or breast-feeding;
• Medical contraindication to treatment with study medication (e.g. for modafinil, history of heart disease, ischemic ECG changes, arrhythmia, hypertension).
• Women of child-bearing potential must agree to use other means of birth control and to have a pregnancy test repeated at least once monthly.
• Known allergy to modafinil or methadone.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Modafinil Plus Contingency Magagement; Modafinil from 200mg up to 400mg plus Contingency Management	Drug: Modafinil; Modafinil is started at 200mg on the first day of week 1 (treatment phase) and increased to 400mg by the end of that week. Subjects will continue to receive 400mg/day for the remainder of the study.; Behavioral: Contingency Management; Subjects in the CM conditions will earn vouchers for providing cocaine-free urine specimens. Subjects will be informed of the urine test results when available and, for subjects in the CM condition, receive a voucher at that time if the sample is negative. Subjects in the CM condition earn a minimum of $3 for each urine sample they submit that is negative for cocaine. Voucher amounts will escalate by $1 per consecutive clean urine sample submitted up to a maximum of $15 per clean sample.; Drug: Methadone; Subjects will be started on 30 mg of methadone and the dose will be increased as tolerated to reach 60 mg at the end of the first 1-2 weeks of the induction phase. Methadone dosing will bestabilized. During methadone maintenance (weeks 1-11 of treatment phase), subjects continue to receive their maintenance doses of methadone plus modafinil or placebo.; Behavioral: cognitive behavioral treatment; All subjects will receive a manual-guided CBT treatment over the course of their 16-week participation. This manual-guided therapy promotes abstinence through a functional analysis of high-risk situations and coping skills training.
PLACEBO_COMPARATOR: Sugar Pill Plus Contingency Management; Placebo: sugar pill	Behavioral: Contingency Management; Subjects in the CM conditions will earn vouchers for providing cocaine-free urine specimens. Subjects will be informed of the urine test results when available and, for subjects in the CM condition, receive a voucher at that time if the sample is negative. Subjects in the CM condition earn a minimum of $3 for each urine sample they submit that is negative for cocaine. Voucher amounts will escalate by $1 per consecutive clean urine sample submitted up to a maximum of $15 per clean sample.; Drug: Methadone; Subjects will be started on 30 mg of methadone and the dose will be increased as tolerated to reach 60 mg at the end of the first 1-2 weeks of the induction phase. Methadone dosing will bestabilized. During methadone maintenance (weeks 1-11 of treatment phase), subjects continue to receive their maintenance doses of methadone plus modafinil or placebo.; Behavioral: cognitive behavioral treatment; All subjects will receive a manual-guided CBT treatment over the course of their 16-week participation. This manual-guided therapy promotes abstinence through a functional analysis of high-risk situations and coping skills training.; Drug: Sugar Pill; placebo, sugar pill will mirror active drug; Other Names: Placebo
ACTIVE_COMPARATOR: Modafinil Plus Voucher Control	Drug: Modafinil; Modafinil is started at 200mg on the first day of week 1 (treatment phase) and increased to 400mg by the end of that week. Subjects will continue to receive 400mg/day for the remainder of the study.; Drug: Methadone; Subjects will be started on 30 mg of methadone and the dose will be increased as tolerated to reach 60 mg at the end of the first 1-2 weeks of the induction phase. Methadone dosing will bestabilized. During methadone maintenance (weeks 1-11 of treatment phase), subjects continue to receive their maintenance doses of methadone plus modafinil or placebo.; Behavioral: cognitive behavioral treatment; All subjects will receive a manual-guided CBT treatment over the course of their 16-week participation. This manual-guided therapy promotes abstinence through a functional analysis of high-risk situations and coping skills training.; Behavioral: Voucher Control; Subjects in the Yoked-Control condition (YC) will be paired with a CM subject. Subjects in the YC condition will be informed that they will receive vouchers according to an unpredictable schedule, and that they cannot control when they will receive these vouchers or how much they will be worth.
PLACEBO_COMPARATOR: Sugar Pill Plus Voucher Control	Drug: Methadone; Subjects will be started on 30 mg of methadone and the dose will be increased as tolerated to reach 60 mg at the end of the first 1-2 weeks of the induction phase. Methadone dosing will bestabilized. During methadone maintenance (weeks 1-11 of treatment phase), subjects continue to receive their maintenance doses of methadone plus modafinil or placebo.; Behavioral: cognitive behavioral treatment; All subjects will receive a manual-guided CBT treatment over the course of their 16-week participation. This manual-guided therapy promotes abstinence through a functional analysis of high-risk situations and coping skills training.; Drug: Sugar Pill; placebo, sugar pill will mirror active drug; Other Names: Placebo; Behavioral: Voucher Control; Subjects in the Yoked-Control condition (YC) will be paired with a CM subject. Subjects in the YC condition will be informed that they will receive vouchers according to an unpredictable schedule, and that they cannot control when they will receive these vouchers or how much they will be worth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Number of Positive Urine Tests	thrice weekly urine tests	up to 12 weeks.
Average Maximum Days Abstinent		up to 84 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Average Number of Days Using a Substance Within Treatment	up to 90 days

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): March 1, 2014

Study Registration Dates

• First Submitted: February 6, 2009
• First Submitted That Met QC Criteria: February 6, 2009
• First Posted (ESTIMATE): February 9, 2009

Study Record Updates

• Last Update Posted (ACTUAL): December 3, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Cocaine; Opiates; Treatment for addiction; Methadone given for opioid dependence
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Antitussive Agents; Wakefulness-Promoting Agents; Methadone; Modafinil
• Other Study ID Numbers: 0705002636; DPMC (Other Identifier: NIDA); R01DA021264 (NIH)

Plan for Individual participant data (IPD)

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