Low Dose Naltrexone-buprenorphine Transfer to Vivitrol Injection in Opioid Dependence (BUP/NXT-VIVI)

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

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.

Study Overview

• Status: Completed
• Conditions: Opiate Dependence
• Intervention / Treatment: Drug: very low dose naltrexone; Drug: extended release naltrexone; Drug: buprenorphine/naloxone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center / Civitan Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Individuals must be capable of giving informed consent and capable of complying with study procedures.
3. 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:

1. Individuals currently prescribed or regularly taking opiates for chronic pain or medical illness.
2. Individuals regularly using licit or illicit methadone or BUP.
3. Individuals meeting DSM-IV criteria for schizophrenia, schizoaffective or psychotic disorders, or psychiatric disorder (other than substance abuse) requiring intervention.
4. Individuals who are medically unstable, or have liver enzyme function tests greater than two times normal.
5. Individuals with current suicidal risk or 1 or more suicide attempts within the past year.
6. 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.
7. 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)
8. Individuals who are dependent on any other drugs (excluding nicotine)
9. Individuals with known sensitivity to BUP, VIVITROL, NTX, naloxone.
10. Individuals who are court-mandated to treatment.
11. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BUP/VLNXT to VIVITROL; 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; 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: extended release naltrexone; 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.; Other Names: Vivitrol; Drug: buprenorphine/naloxone; 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.; Other Names: Suboxone

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Paolo Mannelli
• Collaborators: Alkermes, Inc.
• Investigators: Principal Investigator: Paolo Mannelli, MD, Duke University Health Systems

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: September 19, 2012
• First Submitted That Met QC Criteria: September 19, 2012
• First Posted (Estimate): September 21, 2012

Study Record Updates

• Last Update Posted (Estimate): June 1, 2016
• Last Update Submitted That Met QC Criteria: April 25, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Addiction; Drug Dependence; Opioid Addiction
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Alcohol Deterrents; Buprenorphine; Naltrexone; Naloxone; Buprenorphine, Naloxone Drug Combination
• Other Study ID Numbers: Pro00036909

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No