Addiction Treatment in Russia: Oral vs. Naltrexone Implant

ID: NCT00218426
Status: Active, not recruiting
Phase: Phase 2/Phase 3
Start Date: July 01, 2006
First Submitted: September 16, 2005
Last Updated: February 23, 2018
Results: N/A
Sponsors & Collaborators: University of Pennsylvania, National Institute on Drug Abuse (NIDA), St. Petersburg State Pavlov Medical University and 3 more..
Location: Russian Federation, United States
Conditions: Heroin Dependence, Opioid-Related Disorders
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Study Description

Brief 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 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.
Condition or disease Intervention/treatment Phase

Heroin Dependence

Opioid-Related Disorders

Drug: naltrexone implant
Other Names
Drug: Oral naltrexone
Other Names
Drug: placebo oral and placebo implant
Other Names
Phase 2/Phase 3

Tracking Information

First Submitted DateSeptember 16, 2005
Last Update Posted DateFebruary 23, 2018
Actual Start DateJuly 01, 2006
Anticipated Completion DateOctober 01, 2018
Actual Primary Completion DateJuly 01, 2017
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Relapse to heroin addiction (measured at Months 1 and 6) [Time Frame: 6 months]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Time to dropout for treatment [Time Frame: 6 months]

  • positive opioid urine test [Time Frame: 6 months]

  • use of alcohol and other drugs [Time Frame: 6 months]

  • psychiatric symptoms [Time Frame: 6 months]

  • HIV risk (measured at Months 1, 6, 9, and 12) [Time Frame: 6 months]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleAddiction Treatment in Russia: Oral vs. Naltrexone Implant
Official TitleAddiction Treatment in Russia: Oral and Depot Naltrexone
Brief 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 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.

Study TypeInterventional
Study PhasePhase 2/Phase 3
Estimated Enrollment
306
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
Heroin Dependence
Opioid-Related Disorders
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: naltrexone implant

The implant is 1000 mg naltrexone

Other Names
Drug: Oral naltrexone

oral naltrexone 50 mg/day

Other Names
Drug: placebo oral and placebo implant

placebos resemble active medications

Other Names
Study Groups/Cohorts
ON
Oral naltrexone

DNI
naltrexone implant

ONP
daily placebo oral naltrexone and placebo implant every 8 weeks

Study Arms
Experimental DNI
naltrexone implant
Drug : naltrexone implant
The implant is 1000 mg naltrexone

Active Comparator ON
Oral naltrexone
Drug : Oral naltrexone
oral naltrexone 50 mg/day

Placebo Comparator ONP
daily placebo oral naltrexone and placebo implant every 8 weeks
Drug : placebo oral and placebo implant
placebos resemble active medications

Arm Intervention/Treatment
Experimental DNI
naltrexone implant
Drug : naltrexone implant
Active Comparator ON
Oral naltrexone
Drug : Oral naltrexone
Placebo Comparator ONP
daily placebo oral naltrexone and placebo implant every 8 weeks
Drug : placebo oral and placebo implant

Recruitment Information

Recruitment Status:Active, not recruiting
Enrollment306
Completion DateOctober 01, 2018
Eligibility 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
GenderAll
Age18 Years to 50 Years
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
Russian Federation
United States

Administrative Information

NCT Number:NCT00218426
Other Study ID Numbers
NIDA-17317-1
R01DA017317
R01-17317-1
DPMC
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
University of Pennsylvania
Collaborators
National Institute on Drug Abuse (NIDA)
St. Petersburg State Pavlov Medical University
Leningrad Addiction Treatment & Research Center, Leningrad Region, Russia
Investigators
Principal Investigator
George Woody, MD
University of Pennsylvania