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
  Purpose

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.


Condition Intervention Phase
Heroin Dependence
Opioid-Related Disorders
Drug: naltrexone implant
Drug: Oral naltrexone
Drug: placebo oral and placebo implant
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Addiction Treatment in Russia: Oral and Depot Naltrexone

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Relapse to heroin addiction (measured at Months 1 and 6) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 306
Study Start Date: July 2006
Study Completion Date: October 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ON
Oral naltrexone
Drug: Oral naltrexone
oral naltrexone 50 mg/day
Experimental: DNI
naltrexone implant
Drug: naltrexone implant
The implant is 1000 mg naltrexone
Placebo Comparator: ONP
daily placebo oral naltrexone and placebo implant every 8 weeks
Drug: placebo oral and placebo implant
placebos resemble active medications

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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00218426

Locations
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104 6178
Russian Federation
Pavlov Medical University
St. Petersburg, Russian Federation, 197022
Sponsors and Collaborators
University of Pennsylvania
Pavlov State Medical University, St. Petersburg, Russia
Leningrad Addiction Treatment & Research Center, Leningrad Region, Russia
Investigators
Principal Investigator: George Woody, MD University of Pennsylvania
  More Information

No publications provided

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00218426     History of Changes
Other Study ID Numbers: NIDA-17317-1, R01DA017317, R01-17317-1, DPMC
Study First Received: September 16, 2005
Last Updated: July 3, 2012
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Opioid-Related Disorders
Heroin Dependence
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Naltrexone
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014