Effectiveness of Controlled-Release Morphine for Chronic Neuropathic Pain After Spinal Cord Injury
Condition: Neuropathic Pain; Spinal Cord Injury
MeSH terms: Spinal Cord Injuries; Neuralgia; Wounds and Injuries
Study type: Interventional
Phase: Phase 2

Summary: 
      We would like to learn if a medicine called "modified-release morphine sulfate" (Avinza)
      helps reduce Spinal Cord Injury (SCI)-related pain that has lasted a long time.
      "Modified-release" means that the medicine in the capsules is slowly released to the body,
      instead of being released all at once. Avinza is approved by the Food and Drug Administration
      for the treatment of pain, but we do not know how effective Avinza is in reducing SCI-related
      pain.
    

Detailed description: 
      Neuropathic pain occurs as a result of damage to neural tissue either in the peripheral or in
      the central nervous system. Three types of neuropathic pain after SCI are especially
      difficult to treat: at level central pain (ALCP), at level radicular pain (ALRP), and below
      level central pain (BLCP). Various analgesic medications with distinct mechanisms and sites
      of action are currently used in clinical practice for treatment of neuropathic pain after
      SCI, including antidepressants, anticonvulsants, nonsteroidal anti-inflammatory drugs
      (NSAIDs), and opioids. These analgesic medications, when evaluated in animal models of SCI
      pain and in the treatment of other neuropathic pain states, have been shown to have only
      modest pain reducing effect. This modest effect is seen clinically as the majority of persons
      with SCI receiving these drugs continue to experience pain, which is severe and disabling in
      one third of cases.

      This study proposes to examine the efficacy of oral modified release morphine in reducing
      pain in persons with neuropathic pain after SCI who have not adequately responded to other
      oral pharmacologic, psychologic, or physical interventions. Only subjects who have failed
      prior pain treatment regimes will be enrolled. Failure of pain regimen is defined as the
      presence of pain in spite of medication(s) or other pain treatment, such as biofeedback or
      other psychological or physical therapy interventions prescribed by a physician.

      The following hypothesis will be tested: morphine, when added to non-opioid medications, is
      more effective than placebo in reducing pain and increasing activity and subjective
      well-being, in persons with ALCP, ALRP and BLCP. In order to test this hypothesis, a
      randomized, double blind, placebo-controlled, two period cross-over trial is proposed, during
      which subjects with ALCP, ALRP, and BLCP will receive daily placebo or modified release
      morphine while being closely monitored and assessed for: (1) adverse effects, (2) quality and
      intensity of pain, (3) intensity of allodynia and hyperalgesia, and (4) activity levels and
      well-being.

      All subjects whether assigned to the placebo or active drug will be able to continue any
      previously prescribed or non-prescribed (over-the-counter) non-opioid medication that has
      been taken on a regular basis, without dose change, for at least three weeks prior to study
      entry. These medications may include but are not limited to the analgesics: acetaminophen and
      any non-steroidal anti-inflammatory drugs; local anesthetics- topical patches such as the
      lidocaine patch or otherwise; and adjuvant pain medications of the anti-depressant or
      anticonvulsant classes. Subjects will not be allowed to take any opioid medication, including
      non-opioid-opioid combination analgesics, other than the study drug for the duration of the
      study.
    

Intervention name(s): Modified-release morphine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): During the first three weeks of each treatment (drug or placebo), the dose will be escalated toward a maximally tolerated dose or a dose sufficient to eliminate pain (up to a ceiling dose of 120 mg), whichever is reached first. During the entire fourth and fifth week of each period, subjects will receive their maximally tolerated dose of study medication. During the sixth and seventh weeks, they will undergo a seven-day dose tapering and a seven-day complete washout of the study drug.
Other intervention name(s): Modified-release morphine sulfate
Intervention MeSH terms: Morphine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Morphine; Chronic Pain; Spinal Cord Injury; Neuropathic Pain