Clinical trial NCT00218426: Addiction Treatment in Russia: Oral vs. Naltrexone Implant
Official title: Addiction Treatment in Russia: Oral and Depot Naltrexone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Heroin Dependence
Opioid-Related Disorders
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: St. Petersburg State Pavlov Medical University
First posted: 2005-09-22
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Retention Without Relapse to Heroin Addiction (Measured at Month 6)
timeFrame: 6 months
Secondary outcomes:
measure: Number of Subjects Who Dropped Out of Treatment
timeFrame: 6 months
measure: Positive Opioid Urine Test
timeFrame: 6 months
measure: Use of Alcohol
timeFrame: 6 months
measure: Composite Score of Psychiatric Problems
timeFrame: 6 months
measure: HIV Risk (Baseline)
timeFrame: baseline
measure: Global Assessment Form (GAF)
timeFrame: baseline
measure: Amphetamine Drug Use
timeFrame: baseline
measure: Cocaine Drug Use
timeFrame: baseline
measure: Marijuana Drug Use
timeFrame: baseline
measure: Benzodiazepine Drug Use
timeFrame: baseline
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: St. Petersburg
country: Russian Federation
facility: Pavlov Medical University
Study officials:
affiliation: University of Pennsylvania
name: George Woody, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.