The Effects of Minocycline in Opioid-maintained Patients
Condition: Opioid Dependence; Pain
MeSH terms: Opioid-Related Disorders
Study type: Interventional

Summary: 
      Opioids are the most commonly utilized pharmacological treatment for moderate to severe pain.
      However, their clinical value is hindered by the development of opioid-induced hyperalgesia
      (OIH). OIH manifests as heightened pain sensitivity, and is an increasingly challenging
      drawback to the efficacy of opioid treatment. Although the mechanism of action modulating OIH
      is not completely understood, previous animal studies suggest that this phenomenon is a
      result of proinflammatory responses. Thus, administering an adjunct anti-inflammatory agent
      may attenuate OIH. Minocycline is one such agent; it is a tetracycline derivative antibiotic
      that inhibits microglia activation, nitric oxide (NO) production, and the release of
      pro-inflammatory cytokines and chemokines. In fact, recent evidence suggests that minocycline
      may attenuate the neuroinflammatory effects of opioids while enhancing their antinociceptive
      effects. Therefore, the investigators will determine if minocycline will mitigate OIH in
      methadone-maintained patients.
    

Detailed description: 
      Sixty completers will be recruited through the VA methadone clinic, as well as through the
      APT Foundation Methadone Maintenance Program. After the initial phone screening, potential
      subjects will undergo a comprehensive evaluation which will include medical, psychiatric, and
      drug use histories as well as physical, psychiatric, and laboratory examinations. Laboratory
      examination will include CBC, liver and thyroid function tests, serum electrolytes, BUN,
      creatinine, PT, PTT, urine analysis (including urine pregnancy for women) and urine
      toxicology screening.

      Participants will be terminated from the study following opioid relapse, or use of any other
      psychotropic medications. If participants are noncompliant (no-show, positive urine
      screening, noncompliance with medication protocol/missing more than one dose of
      minocycline/placebo), participation will be terminated.

      This double-blind, randomized clinical trial will randomize male and female veterans and
      non-veterans currently undergoing methadone maintenance treatment for opioid dependence to
      either minocycline (200mg/day) or placebo for 15 days. Upon inclusion, participants will be
      subjected to a pain assessment to evaluate baseline pain thresholds and tolerance: the Cold
      Pressor Test. An experimental treatment of either minocycline or placebo will then be
      initiated and maintained for 15 days. Additionally, at the beginning of Week 2 of treatment,
      participants will be given a Personal Digital Assistant (PDA) an HP iPAQ Pocket PC 2003 Pro
      that will administer Ecological Momentary Assessments (EMA). Using EMA, we can assess change
      in pain sensitivity, withdrawal symptoms and cognitive performance in the participants'
      natural environment, which increases the ecological validity of the study. Participants will
      be asked to return to the laboratory several times a week for the 15 consecutive days that
      they are taking minocycline in order to receive the study medication and to assess changes in
      pain thresholds and tolerance (i.e. to assess the presence, or lack thereof of hyperalgesia).
      Upon completion of experimental treatment, participants will be asked to return a final time
      to undergo pain measurement once more, to assess any changes in pain sensitivity after
      completion of minocycline.
    

Intervention name(s): Minocycline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Minocycline will be compared with placebo; Placebo will be compared with minocycline
Other intervention name(s): tetracycline; sugar pill
Intervention MeSH terms: Minocycline; Tetracycline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Analgesia; pain analgesia; methadone; opiates