Cocaine Dependence
Conditions
Keywords
Treatment for addiction, Methadone given for opioid dependence, Cocaine, Opiates
Brief summary
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.
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.
Interventions
DRUGModafinil
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.
DRUGSugar Pill
placebo, sugar pill will mirror active drug
BEHAVIORALContingency 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.
DRUGMethadone
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.
BEHAVIORALcognitive 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.
BEHAVIORALVoucher 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.
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Positive Urine Tests | up to 12 weeks. | thrice weekly urine tests |
| Average Maximum Days Abstinent | up to 84 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Average Number of Days Using a Substance Within Treatment | up to 90 days |
Countries
United States
Participant flow
Recruitment details
Adult male and female participants were recruited from the Greater New Haven area from May 2008 to March 2014 by word-of-mouth, flyers and from referrals from treatment centers in the local area. The study was conducted in an outpatient clinic of the West Haven VA Hospital.
Pre-assignment details
After eligibility was determined, participants were randomized to placebo, 200mg up to 400mg of modafinil.The study consisted of three phases that involve: 1) a one or two week induction phase, 2) an eleven-week treatment phase; and 3) a four week taper, detoxification or transfer phase.
Participants by arm
| Arm | Count |
|---|---|
| Modafinil Plus CM Modafinil from 200mg up to 400mg
Modafinil: Modafinil will be phase in from 200mg to 400mg | 26 |
| Modafinil Plus Voucher Control Modafinil from 200mg up to 400mg
Modafinil: Modafinil will be phase in from 200mg to 400mg | 19 |
| Sugar Pill Plus CM Placebo: sugar pill
Sugar Pill: placebo, sugar pill will mirror active drug | 19 |
| Sugar Pill Plus Voucher Control Placebo: sugar pill
Sugar Pill: placebo, sugar pill will mirror active drug | 27 |
| Total | 91 |
Baseline characteristics
| Characteristic | Modafinil Plus CM | Modafinil Plus Voucher Control | Sugar Pill Plus CM | Sugar Pill Plus Voucher Control | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 19 Participants | 19 Participants | 27 Participants | 91 Participants |
| Age, Continuous | 38.9 years STANDARD_DEVIATION 10.8 | 41.5 years STANDARD_DEVIATION 9.7 | 34.5 years STANDARD_DEVIATION 10.2 | 38.2 years STANDARD_DEVIATION 11.4 | 38.3 years STANDARD_DEVIATION 10.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 4 Participants | 3 Participants | 4 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 5 Participants | 2 Participants | 8 Participants | 16 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 10 Participants | 14 Participants | 15 Participants | 59 Participants |
| Region of Enrollment United States | 26 participants | 19 participants | 19 participants | 27 participants | 91 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 6 Participants | 11 Participants | 33 Participants |
| Sex: Female, Male Male | 19 Participants | 10 Participants | 13 Participants | 16 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 19 | 0 / 19 | 0 / 27 |
| other Total, other adverse events | 11 / 26 | 8 / 19 | 5 / 19 | 6 / 27 |
| serious Total, serious adverse events | 0 / 26 | 0 / 19 | 0 / 19 | 0 / 27 |
Outcome results
Primary
Average Maximum Days Abstinent
Time frame: up to 84 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Modafinil Plus Contingency Magagement | Average Maximum Days Abstinent | Any opiate | 31.7 days | Standard Deviation 28 |
| Modafinil Plus Contingency Magagement | Average Maximum Days Abstinent | Cocaine | 30.9 days | Standard Deviation 28.2 |
| Modafinil Plus Contingency Magagement | Average Maximum Days Abstinent | Alcohol | 69 days | Standard Deviation 21 |
| Modafinil Plus Contingency Magagement | Average Maximum Days Abstinent | Heroine | 40.7 days | Standard Deviation 30.3 |
| Sugar Pill Plus Contingency Management | Average Maximum Days Abstinent | Cocaine | 32.7 days | Standard Deviation 24.2 |
| Sugar Pill Plus Contingency Management | Average Maximum Days Abstinent | Heroine | 46.2 days | Standard Deviation 31.1 |
| Sugar Pill Plus Contingency Management | Average Maximum Days Abstinent | Alcohol | 58.3 days | Standard Deviation 26.4 |
| Sugar Pill Plus Contingency Management | Average Maximum Days Abstinent | Any opiate | 37.4 days | Standard Deviation 27.8 |
| Modafinil Plus Voucher Control | Average Maximum Days Abstinent | Alcohol | 67.2 days | Standard Deviation 21.9 |
| Modafinil Plus Voucher Control | Average Maximum Days Abstinent | Cocaine | 24.4 days | Standard Deviation 23.3 |
| Modafinil Plus Voucher Control | Average Maximum Days Abstinent | Heroine | 47.6 days | Standard Deviation 33.4 |
| Modafinil Plus Voucher Control | Average Maximum Days Abstinent | Any opiate | 43.5 days | Standard Deviation 31.3 |
| Sugar Pill Plus Voucher Control | Average Maximum Days Abstinent | Cocaine | 34.7 days | Standard Deviation 32.1 |
| Sugar Pill Plus Voucher Control | Average Maximum Days Abstinent | Alcohol | 71.8 days | Standard Deviation 19.6 |
| Sugar Pill Plus Voucher Control | Average Maximum Days Abstinent | Any opiate | 41.4 days | Standard Deviation 32.6 |
| Sugar Pill Plus Voucher Control | Average Maximum Days Abstinent | Heroine | 48.4 days | Standard Deviation 33.2 |
Primary
Average Number of Positive Urine Tests
thrice weekly urine tests
Time frame: up to 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Modafinil Plus Contingency Magagement | Average Number of Positive Urine Tests | Total Tests | 32 urine tests | Standard Deviation 8.4 |
| Modafinil Plus Contingency Magagement | Average Number of Positive Urine Tests | Cocaine | 17.5 urine tests | Standard Deviation 13.6 |
| Modafinil Plus Contingency Magagement | Average Number of Positive Urine Tests | Heroine | 16.9 urine tests | Standard Deviation 13.4 |
| Modafinil Plus Contingency Magagement | Average Number of Positive Urine Tests | Any opiate | 17.7 urine tests | Standard Deviation 13.6 |
| Sugar Pill Plus Contingency Management | Average Number of Positive Urine Tests | Cocaine | 16.1 urine tests | Standard Deviation 11.4 |
| Sugar Pill Plus Contingency Management | Average Number of Positive Urine Tests | Heroine | 11.9 urine tests | Standard Deviation 10.7 |
| Sugar Pill Plus Contingency Management | Average Number of Positive Urine Tests | Any opiate | 12.3 urine tests | Standard Deviation 10.6 |
| Sugar Pill Plus Contingency Management | Average Number of Positive Urine Tests | Total Tests | 30.2 urine tests | Standard Deviation 8.6 |
| Modafinil Plus Voucher Control | Average Number of Positive Urine Tests | Heroine | 12.3 urine tests | Standard Deviation 11.1 |
| Modafinil Plus Voucher Control | Average Number of Positive Urine Tests | Cocaine | 16.9 urine tests | Standard Deviation 10.7 |
| Modafinil Plus Voucher Control | Average Number of Positive Urine Tests | Any opiate | 12.5 urine tests | Standard Deviation 11.1 |
| Modafinil Plus Voucher Control | Average Number of Positive Urine Tests | Total Tests | 28.1 urine tests | Standard Deviation 11.2 |
| Sugar Pill Plus Voucher Control | Average Number of Positive Urine Tests | Any opiate | 14.3 urine tests | Standard Deviation 13.7 |
| Sugar Pill Plus Voucher Control | Average Number of Positive Urine Tests | Cocaine | 15.8 urine tests | Standard Deviation 11.8 |
| Sugar Pill Plus Voucher Control | Average Number of Positive Urine Tests | Total Tests | 31.4 urine tests | Standard Deviation 7.1 |
| Sugar Pill Plus Voucher Control | Average Number of Positive Urine Tests | Heroine | 14 urine tests | Standard Deviation 13.6 |
Secondary
Average Number of Days Using a Substance Within Treatment
Time frame: up to 90 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Modafinil Plus Contingency Magagement | Average Number of Days Using a Substance Within Treatment | Alcohol | 0.32 days | Standard Deviation 0.9 |
| Modafinil Plus Contingency Magagement | Average Number of Days Using a Substance Within Treatment | Cocaine | 19 days | Standard Deviation 19.1 |
| Modafinil Plus Contingency Magagement | Average Number of Days Using a Substance Within Treatment | Heroin | 13.8 days | Standard Deviation 23.4 |
| Modafinil Plus Contingency Magagement | Average Number of Days Using a Substance Within Treatment | Opiate | 21.8 days | Standard Deviation 26 |
| Sugar Pill Plus Contingency Management | Average Number of Days Using a Substance Within Treatment | Cocaine | 15.6 days | Standard Deviation 15.7 |
| Sugar Pill Plus Contingency Management | Average Number of Days Using a Substance Within Treatment | Heroin | 11.4 days | Standard Deviation 17.6 |
| Sugar Pill Plus Contingency Management | Average Number of Days Using a Substance Within Treatment | Opiate | 13.4 days | Standard Deviation 16.8 |
| Sugar Pill Plus Contingency Management | Average Number of Days Using a Substance Within Treatment | Alcohol | 1.8 days | Standard Deviation 5.2 |
| Modafinil Plus Voucher Control | Average Number of Days Using a Substance Within Treatment | Heroin | 10.2 days | Standard Deviation 15.6 |
| Modafinil Plus Voucher Control | Average Number of Days Using a Substance Within Treatment | Cocaine | 18.6 days | Standard Deviation 14.3 |
| Modafinil Plus Voucher Control | Average Number of Days Using a Substance Within Treatment | Opiate | 11.9 days | Standard Deviation 16 |
| Modafinil Plus Voucher Control | Average Number of Days Using a Substance Within Treatment | Alcohol | 0.06 days | Standard Deviation 0.24 |
| Sugar Pill Plus Voucher Control | Average Number of Days Using a Substance Within Treatment | Opiate | 16.4 days | Standard Deviation 23.1 |
| Sugar Pill Plus Voucher Control | Average Number of Days Using a Substance Within Treatment | Cocaine | 20.3 days | Standard Deviation 20.2 |
| Sugar Pill Plus Voucher Control | Average Number of Days Using a Substance Within Treatment | Alcohol | 0.13 days | Standard Deviation 0.34 |
| Sugar Pill Plus Voucher Control | Average Number of Days Using a Substance Within Treatment | Heroin | 11.7 days | Standard Deviation 18.7 |