Neurocognitive Effects of Opiate Agonist Treatment
Condition: Opioid-Related Disorders; HIV; HIV Infections
MeSH terms: Opioid-Related Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to (1) compare the effects of buprenorphine and methadone, two
      types of opioid addiction treatment, on the ability to think and reason among people addicted
      to opiates, and who are either HIV negative or HIV positive; and (2) investigate whether HIV
      infection changes the way opioid treatment affects the ability to think and reason. The
      investigators hypothesize that there will be (1) significant improvement in thinking and
      reasoning ability after starting buprenorphine treatment compared to methadone treatment,
      among participants with and without HIV at 2 and 4 months compared to baseline; and (2) HIV
      positive participants will demonstrate significant improvement in thinking and reasoning
      ability at 2 and 4 months compared to baseline, but that their thinking and reasoning ability
      will still be lower than HIV negative participants.
    

Detailed description: 
      After randomization, each medication will be prescribed and administered by one of these
      experienced clinicians, according to well- established national protocols. Participants will
      be randomized in a 1:1 ratio in variable size blocks of 4-8 via central, computer-generated
      randomization. Given the relatively small sample size, we will randomize in blocks to ensure
      comparison groups of approximately equal size. Because medication type will not be blinded,
      we will vary block size to prevent anticipation of treatment arm assignment. We will also
      stratify randomization by HIV status to ensure equal numbers of HIV-infected persons in each
      arm.

      INTERVENTION DOSE. Doses of buprenorphine and methadone will be adjusted within pre-specified
      ranges to ensure that comparisons between the two treatments are based on individually
      optimized doses.

      Buprenorphine (we will use the buprenorphine/naloxone combination exclusively) will be
      administered at a dose of 8 to 32 mg per day, though we expect most subjects not to exceed 24
      mg per day. These doses approximate methadone doses of 60 to 100 mg daily, which are in the
      upper range of doses generally used in clinical practice, but are well-known to be most
      efficacious and are also most prevalent in DoSA. Since study clinicians will be experienced
      substance abuse treatment providers, some flexibility will be allowed within these
      parameters. Both buprenorphine and methadone will be administered daily as oral medications.

      The study will have two phases: induction/stabilization (weeks 1 - 3) and maintenance (weeks
      4 - 24).

      During dose induction/stabilization, subjects will attend daily visits (Sx/week) with a study
      clinician and receive gradually increasing doses of medication (see below). The first week of
      induction/stabilization will be considered a run-in period; at the conclusion of this week
      participants will complete enrollment in the trial and also complete their first NP research
      visit. The purpose of the run-in period is to ensure that we enroll persons who are able to
      comply with all trial requirements.

      MAINTENANCE PHASE. The maintenance stage of opioid pharmacotherapy begins when a patient is
      responding optimally to medication treatment and routine dosage adjustments are no longer
      needed. Patients at this stage have stopped abusing opioids and many remain on the same
      dosage of treatment medication for many months, whereas others require frequent or occasional
      adjustments. During maintenance (starting on day 22, week 4),subjects in both arms will
      attend the clinic three times per week, on Monday, Wednesday, and Friday, and will receive
      bottles of medication to take home for the other four days of the week. Subjects will receive
      increases in their doses starting in week 4 if they meet pre-established criteria, up to 100
      mg of methadone, and up to 32 mg of buprenorphine.

      Our proposed research plan includes two follow-up visits, three and six months after the
      baseline visit. We anticipate that subjects will still be in the maintenance phase at the
      time of both these visits.
    

Intervention name(s): Buprenorphine; Methadone
Intervention type(s): Drug; Drug
Intervention description(s): Study participants will be randomly assigned 1:1 to buprenorphine (experimental/intervention) or methadone (active comparator). We will stratify by HIV status to ensure an equal number of HIV-infected participants in each group.; Study participants will be randomly assigned 1:1 to buprenorphine (experimental/intervention) or methadone (active comparator). We will stratify by HIV status to ensure an equal number of HIV-infected participants in each group.
Other intervention name(s): Buprenorphine HCl; Methadone Hydrochloride
Intervention MeSH terms: Buprenorphine; Methadone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Buprenorphine; Methadone; Cognition