A Phase 2/3 interventional study of naltrexone implant and oral naltrexone in Heroin Dependence and Opioid-Related Disorders, sponsored by University of Pennsylvania. Completed at 2 sites in 2 countries. Open to participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2019-03-18.
Sponsored by University of Pennsylvania · Phase 2/3, Interventional, and Treatment
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.
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.
90 studies on the registry are indexed under Heroin Dependence; 1 is open to participants now.
This study's enrollment of 306 is above the median of 87 across 57 interventional studies indexed under Heroin Dependence.
Browse Heroin Dependence studies →University of Pennsylvania is the lead sponsor of 1,668 studies on the registry; 235 are open to participants now.
Of its 158 completed or terminated interventional studies of FDA-regulated products, 109 (69%) have results posted.
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Oral naltrexone placebo (ONP) + Depot Naltrexone Implant (DNI) 1000 mg
Drug: naltrexone implant · Drug: oral placebo naltrexone
Oral naltrexone (ON) 50 mg + Depot Naltrexone placebo Implant (DNIP)
Drug: oral naltrexone · Drug: placebo implant
Oral placebo naltrexone + placebo naltrexone implant
Drug: oral placebo naltrexone · Drug: placebo implant
naltrexone implant is 1000 mg naltrexone
Also known as: DNI
oral naltrexone 50 mg/day
Also known as: ON
oral placebo naltrexone resembles active medication
Also known as: ONP
placebo implant resembles active medication
Also known as: DNIP
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.
Time frame: 6 months
Number of Subjects Who Dropped Out of Treatment
Kaplan-Meier survival curves for the event of subjects who dropped out of treatment
Time frame: 6 months
Positive Opioid Urine Test
missed urine tests were imputed to be positive for opiates
Time frame: 6 months
Use of Alcohol
use of alcohol grams per day
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: baseline
Subjects (SS) are from Leningrad Regional Alcoholism and Substance Abuse Treatment Center, Leningrad Region; and St. Petersburg City Alcoholism and Substance Abuse Treatment Center, screened for detoxification and if met study criteria and interested were referred to study on day of discharge. First SS admitted on 7/31/06, last visit was 1/4/09.
| Milestone | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| Started | 102 | 102 | 102 |
| Completed | 54 | 16 | 11 |
| Not completed | 48 | 86 | 91 |
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.
| Participants | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| Retention Without Relapse to Heroin Addiction (Measured at Month 6) | 54 | 16 | 11 |
Kaplan-Meier survival curves for the event of subjects who dropped out of treatment
| participants | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| Number of Subjects Who Dropped Out of Treatment | 54 | 16 | 11 |
missed urine tests were imputed to be positive for opiates
| urine tests | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| Positive Opioid Urine Test | .427 (0.40 to 0.45) | .636 (0.60 to 0.66) | .341 (0.32 to 0.37) |
use of alcohol grams per day
| grams per day | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| Use of Alcohol | 10.2 ± 1.7 | 9.0 ± 1.7 | 9.6 ± 1.6 |
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.
| composite score | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| Composite Score of Psychiatric Problems | 0.19 ± 0.02 | 0.15 ± 0.02 | 0.18 ± 0.02 |
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
| score on a scale | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| HIV Risk (Baseline) | 8.1 ± 0.44 | 8.0 ± 0.47 | 8.7 ± 0.49 |
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.
| score on a scale | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| Global Assessment Form (GAF) | 62.8 ± 0.7 | 64.7 ± 0.8 | 62.5 ± 0.9 |
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).
| Participants | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| Amphetamine Drug Use | 6 | 12 | 18 |
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).
| Participants | ONP + DNI | ON + DNIP | ONP + DNIP |
|---|---|---|---|
| Cocaine Drug Use | 0 | 0 | 0 |
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).
| Participants | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| Marijuana Drug Use | 22 | 35 | 25 |
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).
| Participants | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| Benzodiazepine Drug Use | 10 | 15 | 9 |
Collected over 3 Years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | 0/102 (0%) | 0/102 (0%) | 6/102 (5.9%) |
| DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | 0/102 (0%) | 0/102 (0%) | 17/102 (16.7%) |
| ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant | 0/102 (0%) | 1/102 (1%) | 3/102 (2.9%) |
| Event | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| cholecystectomyEndocrine disorders | 0/102 | 0/102 | 1/102 |
| Event | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant |
|---|---|---|---|
| local site reactionSurgical and medical procedures | 2/102 | 9/102 | 1/102 |
| nauseaGastrointestinal disorders | 1/102 | 4/102 | 2/102 |
| drowsinessNervous system disorders | 0/102 | 2/102 | 0/102 |
| increased liver enzymeHepatobiliary disorders | 0/102 | 2/102 | 0/102 |
| bronchitisRespiratory, thoracic and mediastinal disorders | 2/102 | 0/102 | 0/102 |
| headacheNervous system disorders | 1/102 | 0/102 | 0/102 |
| high blood pressureCardiac disorders | 0/102 | 0/102 | 0/102 |
| Age, Categorical(Participants) | ONP + DNI | ON + DNIP | ONP + DNIP | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 102 | 102 | 102 | 306 |
| >=65 years | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | ONP + DNI | ON + DNIP | ONP + DNIP | Total |
|---|---|---|---|---|
| Mean | 28.0 (18 to 40) | 27.9 (18 to 40) | 28.7 (18 to 40) | 28.2 (18 to 40) |
| Sex: Female, Male(Participants) | ONP + DNI | ON + DNIP | ONP + DNIP | Total |
|---|---|---|---|---|
| Female | 28 | 28 | 28 | 84 |
| Male | 74 | 74 | 74 | 222 |
| Ethnicity (NIH/OMB)(Participants) | ONP + DNI | ON + DNIP | ONP + DNIP | Total |
|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 102 | 102 | 102 | 306 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | ONP + DNI | ON + DNIP | ONP + DNIP | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 |
| White | 102 | 102 | 102 | 306 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | ONP + DNI | ON + DNIP | ONP + DNIP | Total |
|---|---|---|---|---|
| Russia | 102 | 102 | 102 | 360 |
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Studies of the drug tested here: Naltrexone