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| ID | Type | Description | Link |
|---|---|---|---|
| R01DA017317 | U.S. NIH Grant/Contract | View source | |
| R01-17317-1 | |||
| DPMC |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
| St. Petersburg State Pavlov Medical University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ONP + DNI | Active Comparator | Oral naltrexone placebo (ONP) + Depot Naltrexone Implant (DNI) 1000 mg |
|
| ON + DNIP | Active Comparator | Oral naltrexone (ON) 50 mg + Depot Naltrexone placebo Implant (DNIP) |
|
| ONP + DNIP | Placebo Comparator | Oral placebo naltrexone + placebo naltrexone implant |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| naltrexone implant | Drug | naltrexone implant is 1000 mg naltrexone |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Who Dropped Out of Treatment | Kaplan-Meier survival curves for the event of subjects who dropped out of treatment | 6 months |
| Positive Opioid Urine Test | missed urine tests were imputed to be positive for opiates |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| George Woody, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 6178 | United States | ||
| Pavlov Medical University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40342086 | Derived | 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. | |
| 27436632 | Derived | 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. |
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SS were opioid dependent with physiological features for at least 1 year, negative urine for opioids, had ability to give informed consent, not on psychotropic medication, if female, not pregnant, could provide at least 1 relative contact, no significant lab abnormality, and not major psych disorder.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant |
| FG001 | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet |
| FG002 | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant | ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ONP + DNI | Oral naltrexone placebo + Depot Naltrexone Implant 1000 mg naltrexone implant: depot implant is 1000 mg naltrexone placebo oral tablet: placebo oral tablet resembles active medication |
| BG001 | ON + DNIP |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Subjects who remained in treatment without relapse. remaining in treatment = 6 months manualized clinical counseling, plus medication. | Posted | Count of Participants | Participants | 6 months |
|
3 Years
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product. The event need not have a causal relationship to the treatment. Normal withdrawal is not considered an adverse event.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant | Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| cholecystectomy | Endocrine disorders | MedDRA 12.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| headache | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. George E Woody | University of Pennsylvania | 215-746-7702 | woodg@pennmedicine.upenn.edu |
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| ID | Term |
|---|---|
| D006556 | Heroin Dependence |
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D009271 | Naltrexone |
| ID | Term |
|---|---|
| D009270 | Naloxone |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 |
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| oral naltrexone | Drug | oral naltrexone 50 mg/day |
|
|
| oral placebo naltrexone | Drug | oral placebo naltrexone resembles active medication |
|
|
| placebo implant | Drug | placebo implant resembles active medication |
|
|
| 6 months |
| Use of Alcohol | use of alcohol grams per day | 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. | 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 | 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. | 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). | 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). | 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). | 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). | baseline |
| Saint Petersburg |
| 197022 |
| Russia |
Oral naltrexone 50 mg + Depot Naltrexone placebo Implant
oral naltrexone: oral naltrexone 50 mg/day
depot placebo implant: placebo implant resembles active medication
| BG002 | ONP + DNIP | Oral placebo naltrexone + placebo naltrexone implant placebo oral tablet: placebo oral tablet resembles active medication depot placebo implant: placebo implant resembles active medication |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet |
| OG002 | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant | ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant |
|
|
| Secondary | Number of Subjects Who Dropped Out of Treatment | Kaplan-Meier survival curves for the event of subjects who dropped out of treatment | Posted | Number | participants | 6 months |
|
|
|
| Secondary | Positive Opioid Urine Test | missed urine tests were imputed to be positive for opiates | missing = positive; results negative for opioids | Posted | Number | 95% Confidence Interval | urine tests | 6 months | urine tests | urine tests |
|
|
|
| Secondary | Use of Alcohol | use of alcohol grams per day | Posted | Mean | Standard Deviation | 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. | mean of composite score | Posted | Mean | Standard Deviation | composite score | 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 | Posted | Mean | Standard Deviation | score on a scale | 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. | Posted | Mean | Standard Deviation | score on a scale | 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). | Posted | Count of Participants | Participants | 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). | Posted | Count of Participants | Participants | 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). | Posted | Count of Participants | Participants | 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). | Posted | Count of Participants | Participants | baseline |
|
|
|
| 0 |
| 102 |
| 0 |
| 102 |
| 6 |
| 102 |
| EG001 | DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo | naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet | 0 | 102 | 0 | 102 | 17 | 102 |
| EG002 | ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant | ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant | 0 | 102 | 1 | 102 | 3 | 102 |
| drowsiness | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| high blood pressure | Cardiac disorders | MedDRA 12.0 | Systematic Assessment |
|
| increased liver enzyme | Hepatobiliary disorders | MedDRA 12.0 | Systematic Assessment |
|
| bronchitis | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| local site reaction | Surgical and medical procedures | MedDRA 12.0 | Systematic Assessment |
|
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| Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |