Opioid Dependence
Conditions
Keywords
opioid dependence, naltrexone, vivitrol, dronabinol, marinol
Brief summary
The goal of this two-year study is to test the efficacy of dronabinol as an adjunct to maintenance treatment with naltrexone in opioid-dependent individuals. We hypothesize that administering dronabinol during detoxification and during the first few weeks of naltrexone treatment will lead to improved naltrexone tolerability, resulting in better naltrexone compliance and treatment retention, and ultimately a reduction in opioid use and relapse rates.
Detailed description
The goal of this two-year study is to test the efficacy of dronabinol as an adjunct to maintenance treatment with naltrexone in opioid-dependent individuals. We are proposing a randomized, double-blind, placebo controlled, parallel-groups, 8 week study of relapse prevention in opioid-dependent individuals. Participants will be randomized into one of two conditions (1) Naltrexone and Placebo (N=20) and (2) Naltrexone and dronabinol 15 mg bid (N=40). Treatment will be delivered in an outpatient setting except for the initial phase of inpatient detoxification, lasting 8 days. A long-acting, injectable form of naltrexone 380 mg (Vivitrol) will be administered once per month (the total of two injections), while dronabinol or placebo will be taken daily. In addition, patients will receive a psychosocial intervention that will include elements of motivational interviewing and cognitive-behavioral relapse prevention therapy. The primary aim is to test the efficacy of dronabinol in improving tolerability of naltrexone induction and reducing attrition during detoxification and the first two months of naltrexone treatment. The primary outcome will be the severity of opiate withdrawal and craving. The secondary outcome will be will be retention in treatment at study's end.
Interventions
DRUGinjectable naltrexone and dronabinol
Injectable form of naltrexone 380 mg (Vivitrol) will be administered once per month plus dronabinol 15 mg bid for the first 5 weeks of treatment.
DRUGNaltrexone and placebo
Injectable form of naltrexone 380 mg (Vivitrol) will be administered once per month plus placebo bid for 5 weeks.
Sponsors
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Adult, aged 18-60. * 2\. Meets Diagnostic and Statistical Manual -IV criteria for current opiate dependence disorder of at least six months duration, supported by a positive urine for opiates and a positive naloxone challenge test if the diagnosis is unclear. * 3\. Have a history of marijuana use (more than 30 occasions lifetime) * 4\. Voluntarily seeking treatment for opioid dependence * 5\. In otherwise good health based on complete medical history, physical examination, vital signs measurement, ECG, and laboratory tests (hematology, blood chemistry, urinalysis) within normal ranges. * 6\. Able to give informed consent.
Exclusion criteria
* 1\. Physiologically dependent on alcohol or sedative-hypnotics with impending withdrawal. * 2\. Patients meeting current criteria for cannabis abuse or dependence, and those who used cannabis in the week prior to study entry as documented by the positive toxicology * 3\. Current Diagnostic and Statistical Manual -IV criteria of other substance use disorders. Exceptions include cannabis abuse or dependence, nicotine dependence, cocaine abuse or dependence, alcohol abuse or alcohol dependence without physiological dependence as long as opioid dependence is a primary disorder. Alcohol dependence with physiological dependence is exclusionary. * 4\. Significant current suicidal risk or 1 or more suicide attempts within the past year * 5\. History of accidental drug overdose in the last three years defined as an episode of opioid-induced unconsciousness or incapacitation, whether or not medical treatment was sought or received. * 6\. Positive serum pregnancy test, lactation, or unwillingness to use a satisfactory method of birth control * 7\. Active psychiatric disorder which might interfere with participation or make participation hazardous, including Diagnostic and Statistical Manual -IV organic mental disorder, psychotic disorder, or bipolar disorder with mania * 8\. History of allergic reaction, adverse reaction, or sensitivity to any study medication. * 9\. Acute hepatitis with serum glutamic-oxaloacetic transaminase or serum glutamic-pyruvic transaminase \> 3 times the upper end of the laboratory normal range (chronic hepatitis is acceptable as we have found naltrexone treatment well tolerate and safe among patients with chronic hepatitis) * 10\. Currently prescribed or regularly taking opiates for chronic pain or medical illness. * 11\. Current participation in a methadone maintenance treatment program and/or regular use of illicit methadone (\>30 mg per week). * 12\. Current participation in another intensive psychotherapy or substance abuse treatment program or participation in another treatment study. * 13\. Concurrent treatment with psychotropic medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Opiate Withdrawal Measured by the Subjective Opiate Withdrawal Scale (SOWS) . | 3x/week during 8 weeks of the trial or study participation | The Subjective Opiate Withdrawal Scale is a self-administered 16 scale containing 16 symptoms ranging in severity from 0 (not at all) to 4 (extremely). The SOWS total score is the sum of 16 items, ranging from 0 (no opiate withdrawal ) to 64 ( severe opiate withdrawal). Values from multiple assessments during the 8-week outpatient phase were averaged. |
| Retention | retention over 8 weeks. | Of those participants randomized to the naltrexone and dronabinol arm, the number that completed all 8 weeks of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Naltrexone and Placebo A long-acting, injectable form of naltrexone 380 mg (Vivitrol) will be administered once per month while placebo will be taken daily for the first 5 weeks of treatment.
Naltrexone and placebo: Injectable form of naltrexone 380 mg (Vivitrol) will be administered once per month plus placebo bid for 5 weeks. | 20 |
| Naltrexone and Dronabinol A long-acting, injectable form of naltrexone 380 mg (Vivitrol) will be administered once per month (the total of two injections, once at the end of hospitalization, and once at end of first month of outpatient treatment), while dronabinol (15 mg bid) will be taken daily for the first 5 weeks of treatment.
Injectable naltrexone and dronabinol: Injectable form of naltrexone 380 mg (Vivitrol) will be administered once per month plus dronabinol 15 mg bid for the first 5 weeks of treatment. | 40 |
| Total | 60 |
Baseline characteristics
| Characteristic | Naltrexone and Placebo | Naltrexone and Dronabinol | Total |
|---|---|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 11.1 | 38.5 years STANDARD_DEVIATION 11.6 | 38.1 years STANDARD_DEVIATION 11.3 |
| Race/Ethnicity, Customized Black | 2 participants | 3 participants | 5 participants |
| Race/Ethnicity, Customized Hispanic | 5 participants | 13 participants | 18 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized White | 12 participants | 23 participants | 35 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 16 Participants | 34 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 20 | 28 / 40 |
| serious Total, serious adverse events | 2 / 20 | 1 / 40 |
Outcome results
Primary
Opiate Withdrawal Measured by the Subjective Opiate Withdrawal Scale (SOWS) .
The Subjective Opiate Withdrawal Scale is a self-administered 16 scale containing 16 symptoms ranging in severity from 0 (not at all) to 4 (extremely). The SOWS total score is the sum of 16 items, ranging from 0 (no opiate withdrawal ) to 64 ( severe opiate withdrawal). Values from multiple assessments during the 8-week outpatient phase were averaged.
Time frame: 3x/week during 8 weeks of the trial or study participation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Placebo | Opiate Withdrawal Measured by the Subjective Opiate Withdrawal Scale (SOWS) . | 11.16 units on a scale | Standard Deviation 6.13 |
| Naltrexone and Dronabinol | Opiate Withdrawal Measured by the Subjective Opiate Withdrawal Scale (SOWS) . | 13.36 units on a scale | Standard Deviation 10.55 |
Primary
Retention
Of those participants randomized to the naltrexone and dronabinol arm, the number that completed all 8 weeks of treatment.
Time frame: retention over 8 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Naltrexone and Placebo | Retention | 7 participants |
| Naltrexone and Dronabinol | Retention | 14 participants |