Addiction Treatment in Russia: Oral vs. Naltrexone Implant

NCT ID: NCT00218426

Last Updated: 2019-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 306 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2010-11-04

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 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.

Conditions

Heroin Dependence; Opioid-Related Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ONP + DNI

Oral naltrexone placebo (ONP) + Depot Naltrexone Implant (DNI) 1000 mg

Group Type: ACTIVE_COMPARATOR

naltrexone implant

Intervention Type: DRUG

naltrexone implant is 1000 mg naltrexone

oral placebo naltrexone

Intervention Type: DRUG

oral placebo naltrexone resembles active medication

ON + DNIP

Oral naltrexone (ON) 50 mg + Depot Naltrexone placebo Implant (DNIP)

Group Type: ACTIVE_COMPARATOR

oral naltrexone

Intervention Type: DRUG

oral naltrexone 50 mg/day

placebo implant

Intervention Type: DRUG

placebo implant resembles active medication

ONP + DNIP

Oral placebo naltrexone + placebo naltrexone implant

Group Type: PLACEBO_COMPARATOR

oral placebo naltrexone

Intervention Type: DRUG

oral placebo naltrexone resembles active medication

placebo implant

Intervention Type: DRUG

placebo implant resembles active medication

Interventions

naltrexone implant

naltrexone implant is 1000 mg naltrexone

Intervention Type: DRUG

oral naltrexone

oral naltrexone 50 mg/day

Intervention Type: DRUG

oral placebo naltrexone

oral placebo naltrexone resembles active medication

Intervention Type: DRUG

placebo implant

placebo implant resembles active medication

Intervention Type: DRUG

Other Intervention Names

DNI; ON; ONP; DNIP

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

St. Petersburg State Pavlov Medical University

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George Woody, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Pavlov Medical University

Saint Petersburg, , Russia

Countries

United States; Russia

References

Kornor H, Lobmaier PPK, Kunoe N. Sustained-release naltrexone for opioid dependence. Cochrane Database Syst Rev. 2025 May 9;5(5):CD006140. doi: 10.1002/14651858.CD006140.pub3.

Reference Type: DERIVED

PMID: 40342086 (View on PubMed)

Krupitsky E, Zvartau E, Blokhina E, Verbitskaya E, Wahlgren V, Tsoy-Podosenin M, Bushara N, Burakov A, Masalov D, Romanova T, Tyurina A, Palatkin V, Yaroslavtseva T, Pecoraro A, Woody G. Anhedonia, depression, anxiety, and craving in opiate dependent patients stabilized on oral naltrexone or an extended release naltrexone implant. Am J Drug Alcohol Abuse. 2016 Sep;42(5):614-620. doi: 10.1080/00952990.2016.1197231. Epub 2016 Jul 19.

Reference Type: DERIVED

PMID: 27436632 (View on PubMed)

Other Identifiers

R01DA017317

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01-17317-1

Identifier Type: -

Identifier Source: secondary_id

DPMC

Identifier Type: -

Identifier Source: secondary_id

NIDA-17317-1

Identifier Type: -

Identifier Source: org_study_id