Study of the Treatment of Experimental Pain in Opioid Dependent Persons on Methadone or Buprenorphine Maintenance
Condition: Opioid Dependence; Pain; Addiction
MeSH terms: Opioid-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      Pain is very common in persons with a history of addiction, but few studies have examined the
      best treatment of pain in this population. This is a study to determine the pain relief
      provided by intravenous hydromorphone (Dilaudid) or buprenorphine given to persons maintained
      on stable doses of methadone or buprenorphine. Experimental sessions will require overnight
      stays on a residential research unit. In these sessions, persons will be exposed to standard
      experimental pain techniques at baseline and then rate the relief (if any) provided by the
      study medication when exposed to the same techniques. Persons will be asked to participate in
      2 or 3 sessions, each separated by at least 7 days.
    

Detailed description: 
      This research is being done to learn how to better treat pain in people maintained on opioid
      medications, like methadone and buprenorphine (Suboxone ®, Subutex ®). People who take opioid
      medications for long periods of time are known to experience pain differently; and, regular
      amounts of medications may not be enough to treat the pain of these individuals.
      Additionally, many people with a history of addiction are afraid of taking opioid pain
      relievers, like morphine or hydromorphone (Dilaudid ®), for fear of relapse.

      This study will help guide the medical community on better pain treatment for people
      prescribed buprenorphine or methadone. Investigators also want to determine the risk for
      relapse in people who receive opioid pain relievers for the treatment of acute pain.

      Healthy people aged 18-55 who are maintained on buprenorphine or methadone for the treatment
      of opioid dependence may take part in this study. Participants must be free of illicit drug
      use and be on a stable dose of methadone or buprenorphine. Initial screening will occur over
      the phone and then select participants will be scheduled for an in-person screening at the
      BPRU.

      If a participant meets all criteria and agrees to participate, he or she will be enrolled
      into the study. Enrolled participants will have 2 or 3 sessions involving overnight stays on
      the Behavioral Pharmacology Research Unit (BPRU) residential unit.

        -  If participants are on methadone, they will have 2 sessions

        -  If participants are on buprenorphine, they will have 3 sessions.

      Sessions will each last for about 40 hours and involve identical procedures. That means
      participants will stay 2 nights on the BPRU residential unit for each session, and these
      sessions will be at least a week a part. Most people will complete all sessions within 1
      month.

      During sessions participants will experience the following:

      Day 1 - Admission to the BPRU residential unit

        -  Participants will take an alcohol breath test and provide a urine sample to check for
           drug use (and pregnancy if female). These tests must be negative to be admitted.

        -  Vital signs will be measured.

        -  Participants will receive their normal dose of methadone or buprenorphine.

      Day 2 - Experimental pain testing

        -  On each session day, a nurse will insert an IV catheter on the arm or hand not involved
           with pain testing.

        -  Investigational drug or placebo will be given in random order. During each pain testing
           session, participants will receive 4 doses of the same investigational drug or placebo.
           If participants are on methadone, they will not receive buprenorphine injections as
           these could cause opioid withdrawal symptoms. Participants will not be told which drug
           or placebo they are getting and the research staff will not know the assignment either.

        -  Participants will have 7 rounds of experimental pain testing, each lasting about 45
           minutes and consisting of the same pain procedures. A trained technician will show
           participants each of the pain testing procedures and practice with them until
           participants learn what is involved and how to respond. Participants will be asked to
           complete 4 different types of standard pain tests during each session. Participants may
           stop these procedures at any point by telling the technician that they wish to stop.

             1. One type of test will produce pain by a device that will be pressed against the
                skin on the shoulder and arm. This produces pressure, similar to pressing a finger
                against the skin. Participants will be asked to indicate when the pain from the
                pressure reaches certain levels of intensity.

             2. Another type of test will produce pain by a small device that gives off heat. An
                investigator will put this device on a participant's forearm and it will increase
                in temperature. Some of these temperatures will cause participants to experience
                pain, and they will be asked to rate the pain produced by different intensities of
                heat.

             3. The third type of pain test will involve placing a hand in very cold water and
                leaving it there for as long as possible, or until reaching a time limit.
                Participants will be asked to rate the pain that they feel from the cold water and
                they may remove their hand from the water at any time.

             4. In addition to pain tests, investigators will also test the ability to detect
                touch, warmth, and cold sensations. To test for touch sensitivity, a series of very
                fine threads or thread-like objects will be applied to the forearm and
                investigators will ask participants to communicate when first noticing any
                sensation. To test for warmth and cold sensitivity, the same device used to test
                heat pain sensitivity will be placed on the arm. Participants will be asked to let
                the investigator know when they first notice the sensation of warmth or cold.

      At times, participants will experience more than one type of pain at the same time.

        -  Participants will answer questions about their experiences, including questions about
           how the study drug or placebo makes them feel and about any problems with the study drug
           or placebo.

        -  Staff will take a participant's vital signs and take a picture of the eye repeatedly
           over each session.

        -  Unless participants experience symptoms of opioid withdrawal (for example - nausea,
           vomiting, diarrhea or loose stools, body aches, and goosebumps), they will not be given
           the daily dose of methadone or buprenorphine on pain testing day (Day 2).

      Day 3 - Discharge

        -  Vital signs will be measured and a picture of the eye will be taken.

        -  Participants will answer questions about their experiences from Day 2, including
           questions about any lasting drug effects and about any problems with the study drug or
           placebo.

        -  Participants will receive their normal dose of methadone or buprenorphine and be
           discharged from the residential unit.
    

Intervention name(s): Placebo; Hydromorphone; Buprenorphine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Intravenous injection of approximately 5 mL administered via slow push over 5 minutes. Given 4 injections during the session with each injection separated by 1.5 hours.; Intravenous injection of approximately 5 mL administered via slow push over 5 minutes. Given 4 injections during the session with each injection separated by 1.5 hours.; Intravenous injection of approximately 5 mL administered via slow push over 5 minutes. Given 4 injections during the session with each injection separated by 1.5 hours.
Other intervention name(s): Normal Saline; Dilaudid; Suboxone; Subutex
Intervention MeSH terms: Buprenorphine; Hydromorphone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Quantitative sensory testing; Cold pressor test; Opioid dependence; Methadone maintenance; Buprenorphine maintenance; Abuse liability; Diffuse Noxious Inhibitory Controls (DNIC); Temporal Summation