Addiction Treatment in Russia: Oral vs. Naltrexone Implant

University of Pennsylvania

Status and phase: Completed; Phase 3; Phase 2

Conditions: Heroin Dependence; Opioid-Related Disorders

Treatments: Drug: placebo implant; Drug: oral naltrexone; Drug: naltrexone implant; Drug: oral placebo naltrexone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00218426

NIDA-17317-1

R01DA017317 (U.S. NIH Grant/Contract)

R01-17317-1

DPMC

Details and patient eligibility

About

Heroin addiction is a growing problem in Russia; individuals who enter heroin addiction treatment often relapse. Therefore, effective heroin addiction treatments are necessary to prevent relapse. The purpose of this study is to compare oral naltrexone with a naltrexone implant that provides opioid blockade for two months in preventing relapse to heroin addiction in St. Petersburg, Russia.

Full description

The usual treatment of heroin addiction in Russia involves detoxification and 2-4 weeks of rehabilitation with referral to outpatient follow-up. Though most patients complete inpatient treatment, few keep follow-up appointments and relapse rates are high. More effective therapies are needed, especially in view of the epidemic of heroin addiction that has resulted in the spread of HIV and other infectious diseases. A recently-completed study of 52 patients randomized to oral naltrexone (ON) or oral naltrexone placebo (ONP) has shown efficacy in preventing relapse and reducing HIV risk but dropout was a problem with only 44% of ON patients proven to have not relapsed by 6 months (as compared to 16% of ONP patients). A larger study of 280 patients randomized to ON or ONP replicated these results and found some indication that adding an selective serotonin reuptake inhibitor (SSRI) to naltrexone may improve its efficacy in women, probably because they tend to have higher levels of psychiatric symptoms than men.

We think that retention and outcome can be improved by using a longer acting naltrexone preparation, and in this study we propose to compare ON with a depot naltrexone implant (DNI) that is manufactured and approved for use in Russia, and provides opioid blockade for 8-10 weeks. We will use a placebo-controlled, double-blind/double-dummy design since a placebo-controlled trial is required by the Russian equivalent of our FDA as a condition for testing a pharmacotherapy. Participants will be male and female heroin addicts who have been detoxified in addiction treatment hospitals or outpatient settings in St. Petersburg and have a family member willing and able to supervise medication adherence and facilitate follow-up. After giving informed consent and confirming the absence of physiologic dependence, 306 patients will be randomly assigned to a 6-month treatment in one of three groups of 102 each: oral naltrexone (ON) + depot naltrexone implant placebo (DNIP); oral naltrexone placebo (ONP) + depot naltrexone implant (DNI); or ONP + DNIP. All patients will receive biweekly clinical management/adherence enhancement counseling. Assessments will be done at baseline, at each biweekly appointment during the 6-months of medication treatment, and at 3 and 6 months following the end of study medication. Primary outcome will be the relapse free proportion at months 1-6; secondary outcomes will be time to dropout, opioid positive urines, HIV risk, use of alcohol and other drugs, psychiatric symptoms, and other measures of overall adjustment. We hypothesize that outcomes will be better with DNI than ON, and that each will be more effective than placebo.

Enrollment: 306 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Current opioid dependence
• Recently completed opioid detoxification

Exclusion criteria

• Serious medical or psychiatric condition requiring immediate hospitalization or that would make participation in the study hazardous
• Planning to leave the study area within the 12 months following study entry
• Imminent incarceration
• Pregnancy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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306 participants in 3 patient groups, including a placebo group

ONP + DNI

Active Comparator group

Description:

Oral naltrexone placebo (ONP) + Depot Naltrexone Implant (DNI) 1000 mg

Treatment:

Drug: oral placebo naltrexone

Drug: naltrexone implant

ON + DNIP

Active Comparator group

Description:

Oral naltrexone (ON) 50 mg + Depot Naltrexone placebo Implant (DNIP)

Treatment:

Drug: oral naltrexone

Drug: placebo implant

ONP + DNIP

Placebo Comparator group

Description:

Oral placebo naltrexone + placebo naltrexone implant

Treatment:

Drug: oral placebo naltrexone

Drug: placebo implant