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

This study has been completed.
Sponsor:
Collaborator:
Alkermes, Inc.
Information provided by (Responsible Party):
Paolo Mannelli, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01690546
First received: September 19, 2012
Last updated: April 25, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Opiate Dependence
Drug: very low dose naltrexone
Drug: extended release naltrexone
Drug: buprenorphine/naloxone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Flexible Dose Study of Very Low Doses of Naltrexone-Buprenorphine Transfer to Extend-Release Naltrexone (VIVITROL®) in Opioid Addiction

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Retention in Treatment [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Withdrawal Intensity as Measured by the Clinical Opiate Withdrawal Scale (COWS) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

    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.


  • Withdrawal Intensity as Measured by the Subjective Opiate Withdrawal Scale (SOWS) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

    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.


  • Craving [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Illicit Drug Use, Measured by Urine Drug Testing [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    number of participants that tested positive for marijuana, cocaine, and opiates.

  • Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire [ Time Frame: Day 9 ] [ Designated as safety issue: No ]

    Questionnaire consisted of 3 questions.

    1. Were you satisfied with the treatment (range 1-5): Completely satisfied (1) to completely dissatisfied (5).
    2. Were you satisfied with withdrawal treatment (range 1-5): Minimal withdrawal (1) to worse than ever (5).
    3. Did the medication help (range 1-5): Helped a lot (1) to No it did not help (5).

    Lower scores represent greater satisfaction.


  • Percentage of Participants Who Adhered to Study Visits. [ Time Frame: baseline to end of study (approximately 40 days) ] [ Designated as safety issue: No ]
  • Percentage of Participants With Adherence to Medication (Naltrexone) [ Time Frame: Day 1 to Day 8 (+/- 2 days) ] [ Designated as safety issue: No ]
    Participant who took Naltrexone as prescribed.

  • Use of Ancillary Medications. [ Time Frame: baseline to week 1 ] [ Designated as safety issue: No ]
    Number of participants that took ancillary medication

  • Number of Participants That Self Reported Illicit Drug Use [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Participants reported on any illicit drug use to include Cocaine marijuana opiates


Enrollment: 38
Study Start Date: September 2012
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Suboxone

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01690546

Locations
United States, North Carolina
Duke University Medical Center / Civitan Building
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Paolo Mannelli
Alkermes, Inc.
Investigators
Principal Investigator: Paolo Mannelli, MD Duke University Health Systems
  More Information

Responsible Party: Paolo Mannelli, Associate Professor of Psychiatry, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01690546     History of Changes
Other Study ID Numbers: Pro00036909 
Study First Received: September 19, 2012
Results First Received: February 22, 2016
Last Updated: April 25, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Duke University:
Opioid Addiction
Addiction
Drug Dependence

Additional relevant MeSH terms:
Opioid-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Analgesics, Opioid
Buprenorphine
Buprenorphine, Naloxone Drug Combination
Naltrexone
Naloxone
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists

ClinicalTrials.gov processed this record on August 28, 2016