Addiction Treatment in Russia: Oral vs. Naltrexone Implant

February 28, 2019 updated by: University of Pennsylvania

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

306

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • St. Petersburg, Russian Federation, 197022
        • Pavlov Medical University
  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104 6178
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: ONP + DNI
Oral naltrexone placebo (ONP) + Depot Naltrexone Implant (DNI) 1000 mg
Drug: naltrexone implant
naltrexone implant is 1000 mg naltrexone
Other Names:
  • DNI
Drug: oral placebo naltrexone
oral placebo naltrexone resembles active medication
Other Names:
  • ONP
Active Comparator: ON + DNIP
Oral naltrexone (ON) 50 mg + Depot Naltrexone placebo Implant (DNIP)
Drug: oral naltrexone
oral naltrexone 50 mg/day
Other Names:
  • ON
Drug: placebo implant
placebo implant resembles active medication
Other Names:
  • DNIP
Placebo Comparator: ONP + DNIP
Oral placebo naltrexone + placebo naltrexone implant
Drug: oral placebo naltrexone
oral placebo naltrexone resembles active medication
Other Names:
  • ONP
Drug: placebo implant
placebo implant resembles active medication
Other Names:
  • DNIP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Retention Without Relapse to Heroin Addiction (Measured at Month 6)
Time Frame: 6 months
Survival analysis (Kaplan-Meier survival functions with log-rank Cox-Mantel criteria for group comparison was used to determine the primary outcome of retention, defined as not missing 2 consecutive counseling sessions and not having a relapse. Because this outcome combined patients who failed to keep appointments with those who kept appointments but relapsed, the proportion of non-survivors attributable to proven relapse.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects Who Dropped Out of Treatment
Time Frame: 6 months
Kaplan-Meier survival curves for the event of subjects who dropped out of treatment
6 months
Positive Opioid Urine Test
Time Frame: 6 months
missed urine tests were imputed to be positive for opiates
6 months
Use of Alcohol
Time Frame: 6 months
use of alcohol grams per day
6 months
Composite Score of Psychiatric Problems
Time Frame: 6 months
composite score is a decimal score; with 0 = no problems, 1 = the most problems based on the Addiction Severity Index composite score of 11 indexed questions.
6 months
HIV Risk (Baseline)
Time Frame: baseline
The Risk Assessment Behavior (RAB), is an HIV risk Scale. The Total Score is scored by adding the values that correspond to the responses selected by the subject for the items asked. This highest total score is 40 (highest risk), and the lowest score = 0 (no risk). This assessment has 2 Subsections: 1) Drug Risk = 8 questions (lowest Drug Risk score = 0 (no risk), and highest drug risk score = 22 =(greatest risk), 2) 10 Sex Risk questions: scores are 0 = no risk, and 18 = highest risk). Total RAB Score = Drug Risk Total + Sex Risk Total (0 = no risk, 40 = highest). See: Risk Assessment Battery (RAB) Scoring System, https://www.med.upenn.edu/hiv/assets/user-content/.../RABScoringv2.112.21.95.doc
baseline
Global Assessment Form (GAF)
Time Frame: baseline
Assessment of overall psychiatric function comprises Axis V in the DSM-IV (DSM-IV, 1994). GAF scores range from 0 to 100. A reasonably well-functioning person will score above 70; serious impairment is below 50.
baseline
Amphetamine Drug Use
Time Frame: baseline
Number of subjects who used Amphetamine in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).
baseline
Cocaine Drug Use
Time Frame: baseline
Number of subjects with cocaine drug use in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).
baseline
Marijuana Drug Use
Time Frame: baseline
Number of subjects with Marijuana use in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).
baseline
Benzodiazepine Drug Use
Time Frame: baseline
Number of subjects with benzodiazepine drug use in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).
baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

National Institute on Drug Abuse (NIDA)
St. Petersburg State Pavlov Medical University

Investigators

  • Principal Investigator: George Woody, MD, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2006

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

November 4, 2010

Study Registration Dates

First Submitted

September 16, 2005

First Submitted That Met QC Criteria

September 16, 2005

First Posted (Estimate)

September 22, 2005

Study Record Updates

Last Update Posted (Actual)

March 18, 2019

Last Update Submitted That Met QC Criteria

February 28, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIDA-17317-1
  • DPMC (Other Identifier: NIDA)
  • R01DA017317 (U.S. NIH Grant/Contract)
  • R01-17317-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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