Low Dose Naltrexone-buprenorphine Transfer to Vivitrol Injection in Opioid Dependence

Study Overview
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Brief Summary
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The purpose of this study is to evaluate a very low dose naltrexone-buprenorphine treatment to transfer opioid dependent individuals to extended release naltrexone injection (Vivitrol). The hypothesis is that patients will complete the transfer to Vivitrol successfully, finding the treatment acceptable and showing minimal withdrawal discomfort.

Detailed Description
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Thirty-five opioid dependent (OD) volunteers seeking treatment will be enrolled in an open-label, flexible-dosing, outpatient trial at Duke Addictions Program. On days 1-3, participants will receive buprenorphine/naloxone daily at a starting dose of 4mg, progressively decreasing to 2 mg on days 2- 3. Participants will also receive very low dose naltrexone (VLNTX) at a dose of 0.25 mg to 1mg on Days 1-3, 2 to 6 mg on Day 4 and between 10 and 50 mg on Days 5-7. Then a VIVITROL injection, 380 mg, will be administered on Day 8. Evaluations will occur daily for up to 6 hours until 1 day after VIVITROL injection and then weekly for 4 weeks. Patients will receive ancillary medications as needed and weekly psychosocial intervention. At the end of the study, participants will be offered outpatient treatment of OD at the study site, or will be referred to other treatment programs.

Official Title
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An Open Label, Flexible Dose Study of Very Low Doses of Naltrexone-Buprenorphine Transfer to Extend-Release Naltrexone (VIVITROL®) in Opioid Addiction

Conditions
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Opiate Dependence

Intervention / Treatment
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* Drug: very low dose naltrexone
* Drug: extended release naltrexone
* Drug: buprenorphine/naloxone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 18 to 65 years of age who meet DSM-IV criteria for OD of at least six months duration, supported by a positive urine for opiates and a positive naloxone challenge test if the diagnosis is unclear. Individuals must be capable of giving informed consent and capable of complying with study procedures. Participants will be asked to provide locator information including the address and telephone number of a non-drug abusing relative or friend who can reach the participant in emergencies. Exclusion Criteria: Individuals currently prescribed or regularly taking opiates for chronic pain or medical illness. Individuals regularly using licit or illicit methadone or BUP. Individuals meeting DSM-IV criteria for schizophrenia, schizoaffective or psychotic disorders, or psychiatric disorder (other than substance abuse) requiring intervention. Individuals who are medically unstable, or have liver enzyme function tests greater than two times normal. Individuals with current suicidal risk or 1 or more suicide attempts within the past year. History of accidental drug overdose in the last three years or any other significant history of overdose following detoxification, defined as an episode of opioid-induced unconsciousness or incapacitation. Nursing/pregnant women, or failure in a sexually active man or woman to use adequate contraceptive methods (e.g., oral or depot contraceptives, foam, sponges, and/or condoms) Individuals who are dependent on any other drugs (excluding nicotine) Individuals with known sensitivity to BUP, VIVITROL, NTX, naloxone. Individuals who are court-mandated to treatment. Individuals who have a current or pending legal status, or any other condition that would make them unlikely to be available for the duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BUP/VLNXT to VIVITROL<br>On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg. | Drug: very low dose naltrexone<br>* On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.<br>Drug: extended release naltrexone<br>* On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.<br>* Other names: Vivitrol;Drug: buprenorphine/naloxone<br>* On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.<br>* Other names: Suboxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention in Treatment | After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Withdrawal Intensity as Measured by the Clinical Opiate Withdrawal Scale (COWS) | After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment. COWS rates eleven common opiate withdrawal signs or symptoms. The summed scores ranged from 0-48, with 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal. | 4 weeks | 
| Withdrawal Intensity as Measured by the Subjective Opiate Withdrawal Scale (SOWS) | After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment. SOWS contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). Total score range is 0 - 64; the higher the score the more withdrawal symptoms. | 4 weeks | 
| Craving | Craving, assessed with a 100-point Visual Analog Scale (VAS), ranging from 'not at all' (0) to 'more than ever' (100). The higher the score the higher the craving. | 4 weeks | 
| Illicit Drug Use, Measured by Urine Drug Testing | number of participants that tested positive for marijuana, cocaine, and opiates. | 4 weeks | 
| Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire | Questionnaire consisted of 3 questions. Were you satisfied with the treatment (range 1-5): Completely satisfied (1) to completely dissatisfied (5). Were you satisfied with withdrawal treatment (range 1-5): Minimal withdrawal (1) to worse than ever (5). Did the medication help (range 1-5): Helped a lot (1) to No it did not help (5). Lower scores represent greater satisfaction. | Day 9 | 
| Percentage of Participants Who Adhered to Study Visits. |  | baseline to end of study (approximately 40 days) | 
| Percentage of Participants With Adherence to Medication (Naltrexone) | Participant who took Naltrexone as prescribed. | Day 1 to Day 8 (+/- 2 days) | 
| Use of Ancillary Medications. | Number of participants that took ancillary medication | baseline to week 1 | 
| Number of Participants That Self Reported Illicit Drug Use | Participants reported on any illicit drug use to include Cocaine marijuana opiates | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid Addiction, Addiction, Drug Dependence