A Strategy to Improve Success of Treatment Discontinuation in Buprenorphine Responders
Condition: Opioid-use Disorder
MeSH terms: Opioid-Related Disorders
Intervention: Vivitrol; Buprenorphine
Intervention description: Oral naltrexone induction procedure followed by Vivitrol; 5-week buprenorphine taper
Intervention MeSH terms: Buprenorphine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: buprenorphine; naltrexone; Vivitrol; opioid dependence

Summary:

      This study is an open--label randomized outpatient trial to evaluate feasibility and efficacy
      of rapid buprenorphine (BUP) discontinuation followed by brief course of treatment with
      long--acting naltrexone (XR--NTX) and to compare it to the standard method of gradual BUP
      taper.Individuals with opioid use disorder (OUD) (N=60) who have successfully completed at
      least 6 months of buprenorphine treatment and do not wish to remain in a long--term
      buprenorphine maintenance program will be recruited. The first phase includes a 4--week
      period of stabilization on buprenorphine 4--8 mg at the research clinic to assure that
      patients are stable, compliant, and free from illicit opioids. Participants that meet the
      above criteria will be randomized 1:1 to: 1) buprenorphine discontinuation and outpatient
      transition to XR--NTX with 3 monthly injections, or 2) buprenorphine discontinuation using a
      gradual 5-week long taper. In both groups participants will receive weekly relapse prevention
      therapy and will be monitored for the duration of the trial, which is 25 weeks post
      randomization.
    

Eligibility criteria:

        Inclusion Criteria:

          1. A documented history of treatment with buprenorphine or buprenorphine/naloxone for at
             least 6 months with sustained abstinence from illicit opioids for at least 3 months.
             Participants must be maintained on daily dose of buprenorphine in the 4--8 mg
             range.(MINI interview by therapist, Clinical interview by psychiatrist, consultation
             with previous prescriber or the verification patients's self-report with the
             prescribing records (PMP) with patient's permission).

          2. Aged 18 to 60 years (Clinical interview).

          3. In otherwise good health based on complete medical history, physical examination,
             vital signs measurement, ECG, and laboratory tests (hematology, blood chemistry,
             urinalysis) within normal ranges (Medical history and physical examination by
             psychiatrist or NP, laboratory tests (serum Chem-20 and CBC, urinalysis), ECG).

          4. Seeking buprenorphine discontinuation and willing to accept randomization to either
             taper from buprenorphine or injection naltrexone (clinical interview).

        Exclusion Criteria:

          1. Lifetime history of DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or
             bipolar disorder (MINI interview by therapist, Clinical interview by psychiatrist).

          2. Current DSM-5 criteria for any other psychiatric disorder that in the investigator's
             judgment is unstable, would be disrupted by the study medication, or is likely to
             require pharmacotherapy or psychotherapy during the study period. Concurrent treatment
             with other psychotropic medication is exclusionary. ( MINI interview by therapist,
             Clinical interview and mental status exam by psychiatrist, contact with collateral
             information as needed and available).

          3. Individuals who meet DSM-5 criteria for any substance use disorders - severe, other
             than opioid and nicotine use disorder. Physiological dependence on alcohol or
             sedative-hypnotics is exclusionary. (MINI interview by therapist, Clinical interview
             by psychiatrist).

          4. A recent history of binge-use of alcohol or sedative-hypnotics (using large amounts in
             a short time to severe intoxication or blackouts). (Clinical interview by
             psychiatrist).

          5. Pregnancy, lactation, or failure to use adequate contraceptive method in female
             patients who are currently engaging in sexual activity with men. ( Clinical interview
             by psychiatrist, physical examination and medical history by psychiatrist or NP, urine
             pregnancy test, serum HCG).

          6. Unstable medical conditions, such as AIDS, cancer, uncontrolled hypertension (blood
             pressure > 140/90), uncontrolled diabetes, pulmonary hypertension or heart disease.
             (Medical history and physical examination by psychiatrist or NP, laboratory tests
             (serum Chem-20 and CBC, urinalysis), ECG).

          7. Legally mandated to participate in a substance use disorder treatment program (
             Participant self-report, Clinical interview by psychiatrist).

          8. Current or recent history of significant violent or suicidal behavior, risk for
             suicide or homicide (MINI interview by therapist, Clinical interview by psychiatrist).

          9. History of accidental opioid overdose in the last three years or any other significant
             history of overdose following detoxification within past 10 years defined as an
             episode of opioid-induced unconsciousness, whether or not medical treatment was sought
             or received. ( MINI interview by therapist, Clinical interview by psychiatrist).

         10. Elevated liver function tests (AST and ALT > 3 times the upper limit of normal) (
             Laboratory tests -serum Chem-20).

         11. Known history of allergy, intolerance, or hypersensitivity to naltrexone or any other
             study medications( Participant self-report, Clinical interview by psychiatrist).