Long Acting Naltrexone for Opioid Addiction: Focus on Sustained Abstinence and Recovery
Condition: Opioid-use Disorder
MeSH terms: Opioid-Related Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      This study is designed as an open-label evaluation of how treatment with XR-NTX may influence
      the quality and speed of recovery of opioid dependent individuals - in a context of a
      naturalistic clinical treatment of opioid dependence. The study will assess recovery outcomes
      and compare these with the clinical effectiveness of XR-NTX (use of illicit substances and
      safety). Further, the study will assess the recovery outcomes in matched controls receiving
      treatment with buprenorphine or buprenorphine-naloxone and enrolled in the national OMT
      program, and compare this with participants receiving XR-NTX.
    

Detailed description: 
      This is a multicenter, open-label, treatment study of how treatment with extended-release
      naltrexone hydrochloride injectable suspension (Vivitrol®) (later referred to as XR-NTX) 380
      mg/4 weeks will influence or promote the psycho-social recovery and somatic and psychiatric
      health in opioid dependent individuals. Further the study will investigate the effectiveness
      and safety of XR-NTX treatment given in a naturalistic setting as an alternative to OMT. The
      study period is 24 weeks, a subsequent 28 week follow up study and a 1 year post-treatment
      study. The study is composed of four"Work Packages" (WP). From the same participating sites,
      a control group of 150 subjects matched on age and gender and currently enrolled in the OMT
      program receiving daily treatment with either oral buprenorphine or buprenorphine-naloxone
      will be recruited. Controls will be compared with study participants on psycho-social aspects
      of recovery and mental and somatic health.

      WP1 will use XR-NTX in a clinical naturalistic setting to describe change or improvement in
      recovery and in illicit drug use for this novel treatment of opioid dependent subjects. A
      total of n=150 participants will be recruited from five urban hospitals and community health
      services in Norway to receive treatment with XR-NTX. From the same hospitals and community
      health services we will also recruit a control group of 150 subjects matched on age and
      gender already enrolled in the OMT and receiving flexible dose of buprenorphine or
      buprenorphine-naloxone. The control group will be used for outcomes related to psycho-social
      recovery and health issues only. There will not be any comparison of use of illicit
      substances between the XR-NTX and control group. After inclusion in the study and a baseline
      assessment, the XR-NTX subjects will be followed-up on a monthly basis by the Principal
      investigator or delegated site personnel. At each visit an injection of XR-NTX will be
      administered and through an interview, data will be obtained on the use of heroin and other
      illicit substances, physical and mental health, housing and family situation, income and
      other social aspects. A urine or saliva sample will be obtained at every visit and screened
      for opioids and other illicit substances. Fertile women will in addition be screened for
      pregnancy. All participants will be followed up at 6 and 12 months post-treatment.

      The comparison group will be assessed at baseline, after 24 weeks and after 52 weeks only.
      Study personnel will not administer any medication to subjects in the comparison group.

      From XR-NTX participants, a saliva sample will be obtained at baseline (or at a later visit)
      for genetic analyses to identify possible genetic biomarkers that may predict the outcome of
      treatment with XR-NTX and possible markers of low catecholaminergic expression
      (ADHD-spectrum) Community health services from each catchment area that facilitate the
      recovery process involving community- and specialized health services, will be invited to
      participate in the study to assess the XR-NTX participants' recovery process every 4 weeks.

      Controls will be assessed by the same community health services on their longer term recovery
      process at week 24 and at week 52.

      Assessment of the descriptive elements in the participant's recovery process will be
      performed using brief structured interviews with the involved health-and social workers.
      Interviews can be done by telephone or on the net such as teleconference, if feasible.

      WP 2 will use qualitative interviews to investigate the subjects' perspective on enablers and
      barriers to agreeing to and remaining in treatment with, a long-acting opioid receptor
      antagonist (XR-NTX), including possible emotional reactions and psycho-social implications of
      treatment. Data will be collected through a) individual semi-structured interviews with
      approximately 40 of the 150 XR-NTX participants: 20 subjects who stay in treatment for more
      than 12 weeks and 20 subjects who receive at least one injection XR-NTX but drop out before
      12 weeks. In addition, individual interviews and focus group interviews, each with 6-8 close
      relatives of study subjects will be performed in order to investigate their conceptions
      regarding the recovery process of their opioid addicted family member; possible changes in
      familial cohesion and social relationships, and their own need for support and follow-up.

      WP 3 is a health-economic study on the cost of XR-NTX treatment in study participants
      compared to treatment with buprenorphine or buprenorphine-naloxone (OMT) in the controls.
      Since the cost of medication is only one part of the total health cost of opioid dependence,
      we will try to estimate the total cost of health- and social services for this group of
      participants based on national registry data, hospital records and records from GPs and
      social workers. Registry-based information will be collected based on participants' personal
      identity number (PIN).

      WP4 is designed to increase the knowledge on how opioid receptor antagonism with XR-NTX
      affects stress, pain and reward responses in patients. WP4 will use specifically measurements
      of physiological and behavioural responses to stimuli known to be modulated by the brain's
      opioid system such as social stressors, physical pain and rewards. In addition, data on
      personality and history of adverse events during childhood that may also be important
      predictors for adherence to treatment will be collected.
    

Intervention name(s): Extended release naltrexone
Intervention type(s): Drug
Intervention description(s): 380mg injectable extended release naltrexone every four weeks
Other intervention name(s): Vivitrol
Intervention MeSH terms: Naltrexone
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: A multicenter, open-label treatment study. Extended-release naltrexone hydrochloride injectable suspension (Vivitrol®) (later referred to as XR-NTX) 380 mg/4 weeks One control group enrolled in the national ART program receives "treatment as usual"; flexible dose of daily oral buprenorphine or buprenorphine-naloxone in line with the clinical guidelines in Norway
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Extended release naltrexone; Opioid dependence; Recovery; Health economics