Addiction Treatment in Russia: Oral vs. Naltrexone Implant
Condition: Heroin Dependence; Opioid-Related Disorders
MeSH terms: Opioid-Related Disorders; Heroin Dependence
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      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.
    

Detailed 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.
    

Intervention name(s): naltrexone implant; oral naltrexone; oral placebo naltrexone; placebo implant
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): naltrexone implant is 1000 mg naltrexone; oral naltrexone 50 mg/day; oral placebo naltrexone resembles active medication; placebo implant resembles active medication
Other intervention name(s): DNI; ON; ONP; DNIP
Intervention MeSH terms: Naltrexone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment