Heroin DependencePhase 2/3NCT00218426

Addiction Treatment in Russia: Oral vs. Naltrexone Implant

A Phase 2/3 study testing naltrexone implant and oral naltrexone in people with Heroin Dependence and Opioid-Related Disorders, run by University of Pennsylvania at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 50 years
Conditions the study is for: Heroin Dependence, Opioid-Related Disorders
What is being tested?: naltrexone implant and oral naltrexone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 306 participants
Where: 2 sitesin 2 countries
Study dates: Jul 2006to 4 Nov 2010
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Current opioid dependence
Recently completed opioid detoxification

Who cannot join

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

Trial locations and contacts

2 sites in 2 countries.

Country

City, postcode or hospital

2 sites in 2 countries

United States1 site

University of Pennsylvania
Philadelphia, Pennsylvania, 19104 6178

Other trials in United States

Russia1 site

Pavlov Medical University
Saint Petersburg, 197022

Other trials in Russia

About this study

Official title: 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.

Read the 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
Being tested: naltrexone implant, oral naltrexone, oral placebo naltrexone, placebo implant
Medical subject headings: Heroin Dependence, Opioid-Related Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

naltrexone implantDrug
Also called DNI
naltrexone implant is 1000 mg naltrexone
oral naltrexoneDrug
Also called ON
oral naltrexone 50 mg/day
oral placebo naltrexoneDrug
Also called ONP
oral placebo naltrexone resembles active medication
placebo implantDrug
Also called DNIP
placebo implant resembles active medication

Study groups in NCT00218426
Study group	Role	What they receive
ONP + DNI	Active comparator	Oral naltrexone placebo (ONP) + Depot Naltrexone Implant (DNI) 1000 mg Receives: Drug: naltrexone implant; Drug: oral placebo naltrexone
ON + DNIP	Active comparator	Oral naltrexone (ON) 50 mg + Depot Naltrexone placebo Implant (DNIP) Receives: Drug: oral naltrexone; Drug: placebo implant
ONP + DNIP	Placebo comparator	Oral placebo naltrexone + placebo naltrexone implant Receives: Drug: oral placebo naltrexone; Drug: placebo implant

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 6 months

Secondary outcomes (10)

Number of Subjects Who Dropped Out of Treatment
Kaplan-Meier survival curves for the event of subjects who dropped out of treatment
Measured: 6 months
Positive Opioid Urine Test
missed urine tests were imputed to be positive for opiates
Measured: 6 months
Use of Alcohol
use of alcohol grams per day
Measured: 6 months
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.
Measured: 6 months
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
Measured: baseline
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.
Measured: baseline
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).
Measured: baseline
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).
Measured: baseline
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).
Measured: baseline
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).
Measured: baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 20064 Nov 2010

First posted22 Sep 2005 (estimated)
Study startJul 2006
Primary completionJun 2009
Study completion4 Nov 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Heroin DependenceStudies of the same condition, open and under way.
More trials run by University of PennsylvaniaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 306 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00218426
Sponsor's protocol ID: NIDA-17317-1
Other IDs: R01DA017317, R01-17317-1, DPMC
Status last verified: Feb 2019
First submitted: 16 Sep 2005
Last updated: 18 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 40342086
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.
PubMed 27436632

Study at a glance

From the registry record, last updated by the sponsor on 18 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Addiction Treatment in Russia: Oral and Depot Naltrexone
ClinicalTrials.gov ID: NCT00218426
Acronym / sponsor ID: NIDA-17317-1
Conditions: Heroin Dependence, Opioid-Related Disorders
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 306 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA), St. Petersburg State Pavlov Medical University
Study start: Jul 2006 (actual)
Primary completion: Jun 2009 (actual)
Study completion: 4 Nov 2010 (actual)
First posted: 22 Sep 2005 (estimated)
Results: Posted 27 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
ONP + DNI	Active comparator	Drug: naltrexone implant, Drug: oral placebo naltrexoneOral naltrexone placebo (ONP) + Depot Naltrexone Implant (DNI) 1000 mg
ON + DNIP	Active comparator	Drug: oral naltrexone, Drug: placebo implantOral naltrexone (ON) 50 mg + Depot Naltrexone placebo Implant (DNIP)
ONP + DNIP	Placebo comparator	Drug: oral placebo naltrexone, Drug: placebo implantOral placebo naltrexone + placebo naltrexone implant

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (2 listed)

Current opioid dependence
Recently completed opioid detoxification

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
naltrexone implantAlso: DNInaltrexone implant is 1000 mg naltrexone	Drug	ONP + DNI
oral naltrexoneAlso: ONoral naltrexone 50 mg/day	Drug	ON + DNIP
oral placebo naltrexoneAlso: ONPoral placebo naltrexone resembles active medication	Drug	ONP + DNI, ONP + DNIP
placebo implantAlso: DNIPplacebo implant resembles active medication	Drug	ON + DNIP, ONP + DNIP

Primary outcome

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.

10 secondary outcomes

Number of Subjects Who Dropped Out of Treatment
Time frame: 6 months
Positive Opioid Urine Test
Time frame: 6 months
Use of Alcohol
Time frame: 6 months
Composite Score of Psychiatric Problems
Time frame: 6 months
HIV Risk (Baseline)
Time frame: baseline
Global Assessment Form (GAF)
Time frame: baseline
Amphetamine Drug Use
Time frame: baseline
Cocaine Drug Use
Time frame: baseline
Marijuana Drug Use
Time frame: baseline
Benzodiazepine Drug Use
Time frame: baseline

Results and safety

Results posted to the registry on 27 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	102	54
DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	102	16
ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant	102	11

Primary outcome: Retention Without Relapse to Heroin Addiction (Measured at Month 6)

Time frame: 6 months. Count of participants. Unit: Participants

Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n = 102	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n = 102	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n = 102
Value	54	16	11

Population analysed: Subjects who remained in treatment without relapse. remaining in treatment = 6 months manualized clinical counseling, plus medication.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: 3 Years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	0 of 102 (0%)	6 of 102 (5.9%)	0 of 102
DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	0 of 102 (0%)	17 of 102 (16.7%)	0 of 102
ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant	1 of 102 (1%)	3 of 102 (2.9%)	0 of 102

Limitations and caveats (from the sponsor): Limitations include limited amount of data on patients who did not remain in treatment, thus making it difficult to obtain more accurate information on the proportions with relapse at 9- and 12- month follow-ups and other secondary outcomes.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40342086Kornor 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.
Derived from this study: PubMed 27436632Krupitsky 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

George Woody, MD principal investigator

University of Pennsylvania

2 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing naltrexone implant and oral naltrexone in people with Heroin Dependence and Opioid-Related Disorders, run by University of Pennsylvania at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Retention Without Relapse to Heroin Addiction (Measured at Month 6) (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00218426, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2019.