Addiction Treatment in Russia: Oral vs. Naltrexone Implant

This study has been completed.
Sponsor:
Collaborators:
Pavlov State Medical University, St. Petersburg, Russia
Leningrad Addiction Treatment & Research Center, Leningrad Region, Russia
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00218426
First received: September 16, 2005
Last updated: July 3, 2012
Last verified: January 2012

September 16, 2005
July 3, 2012
July 2006
July 2009   (final data collection date for primary outcome measure)
Relapse to heroin addiction (measured at Months 1 and 6) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Relapse to heroin addiction
Complete list of historical versions of study NCT00218426 on ClinicalTrials.gov Archive Site
  • Time to dropout for treatment [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • positive opioid urine test [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • use of alcohol and other drugs [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • psychiatric symptoms [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • HIV risk (measured at Months 1, 6, 9, and 12) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
Addiction Treatment in Russia: Oral vs. Naltrexone Implant
Addiction Treatment in Russia: Oral and Depot Naltrexone

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.

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 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, 300 patients will be randomly assigned to a 6-month treatment in one of three groups of 100 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.

An interim analysis was done on the first 190 patients who completed the study and found a significant effect on relapse prevention of the naltrexone implant as compared to oral and placebo naltrexone, with corresponding risk reduction in HIV risk injection practices. There was a slight trend for oral naltrexone vs. placebo for relapse prevention, but unlike our earlier studies, it was not significant. We think that the apparent loss of efficacy for oral naltrexone is because the patients are now older and it is more difficult to enlist their mothers and other close relatives in supervising adherence. These preliminary findings were presented at the 2009 CPDD meeting in Reno, NV.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Heroin Dependence
  • Opioid-Related Disorders
  • Drug: naltrexone implant
    The implant is 1000 mg naltrexone
  • Drug: Oral naltrexone
    oral naltrexone 50 mg/day
  • Drug: placebo oral and placebo implant
    placebos resemble active medications
  • Active Comparator: ON
    Oral naltrexone
    Intervention: Drug: Oral naltrexone
  • Experimental: DNI
    naltrexone implant
    Intervention: Drug: naltrexone implant
  • Placebo Comparator: ONP
    daily placebo oral naltrexone and placebo implant every 8 weeks
    Intervention: Drug: placebo oral and placebo implant
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
306
October 2009
July 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 50 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Russian Federation
 
NCT00218426
NIDA-17317-1, R01DA017317, R01-17317-1, DPMC
Yes
University of Pennsylvania
University of Pennsylvania
  • National Institute on Drug Abuse (NIDA)
  • Pavlov State Medical University, St. Petersburg, Russia
  • Leningrad Addiction Treatment & Research Center, Leningrad Region, Russia
Principal Investigator: George Woody, MD University of Pennsylvania
University of Pennsylvania
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP