Addiction Treatment in Russia: Oral vs. Naltrexone Implant

Opioid-Related Disorders Clinical Trial

Official title:

Addiction Treatment in Russia: Oral and Depot Naltrexone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00218426
• Other study ID #: NIDA-17317-1
• Secondary ID: R01DA017317R01-1
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 2006
• Est. completion date: November 4, 2010

Study information

• Verified date: February 2019
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 306
• Est. completion date: November 4, 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Heroin Dependence
• Opioid-Related Disorders

Intervention

Drug:
• naltrexone implant
naltrexone implant is 1000 mg naltrexone
• oral naltrexone
oral naltrexone 50 mg/day
• oral placebo naltrexone
oral placebo naltrexone resembles active medication
• placebo implant
placebo implant resembles active medication

Locations

Country	Name	City	State
Russian Federation	Pavlov Medical University	St. Petersburg
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
University of Pennsylvania	National Institute on Drug Abuse (NIDA), St. Petersburg State Pavlov Medical University

Countries where clinical trial is conducted

United States,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Retention Without Relapse to Heroin Addiction (Measured at Month 6)	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	Number of Subjects Who Dropped Out of Treatment	Kaplan-Meier survival curves for the event of subjects who dropped out of treatment	6 months
Secondary	Positive Opioid Urine Test	missed urine tests were imputed to be positive for opiates	6 months
Secondary	Use of Alcohol	use of alcohol grams per day	6 months
Secondary	Composite Score of Psychiatric Problems	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
Secondary	HIV Risk (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
Secondary	Global Assessment Form (GAF)	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
Secondary	Amphetamine Drug Use	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
Secondary	Cocaine Drug Use	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
Secondary	Marijuana Drug Use	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
Secondary	Benzodiazepine Drug Use	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

External Links

•   A.T. McLellan, 1986. Addiction Severity Composite Scores Rating Manual