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Effectiveness of Controlled-Release Morphine for Chronic Neuropathic Pain After Spinal Cord Injury

This study has been completed.
Sponsor:
Collaborator:
U.S. Department of Education
Information provided by (Responsible Party):
Thomas N. Bryce, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier:
NCT00488969
First received: June 19, 2007
Last updated: March 18, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Neuropathic Pain
Spinal Cord Injury
Drug: Modified-release morphine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effectiveness of Controlled-Release Morphine for Chronic Neuropathic Pain After Spinal Cord Injury

Resource links provided by NLM:


Further study details as provided by Icahn School of Medicine at Mount Sinai:

Primary Outcome Measures:
  • Pain severity [ Time Frame: Average of daily ratings over 14 days ] [ Designated as safety issue: No ]
    Pain severity rated using a 0-10 Numeric Rating Scale (NRS)


Secondary Outcome Measures:
  • Short McGill Pain Questionnaire (modified) (SF-McGill) [ Time Frame: up to 14 weeks ] [ Designated as safety issue: No ]
  • Opioids cognitive effects scale [ Time Frame: up to 14 weeks ] [ Designated as safety issue: No ]
  • Patient Generated Index for activity (PGI) [ Time Frame: up to 14 weeks ] [ Designated as safety issue: No ]
  • Daily number of attacks of paroxysmal pain [ Time Frame: up to 14 weeks ] [ Designated as safety issue: No ]
  • Quantitative sensory testing [ Time Frame: up to 14 weeks ] [ Designated as safety issue: No ]
    Allodynia, hyperalgesia, and temporal summation (determined using quantitative sensory testing)

  • Subject global impression of change [ Time Frame: up to 14 weeks ] [ Designated as safety issue: No ]
  • Short-Form 36 (SF-36) [ Time Frame: up to 14 weeks ] [ Designated as safety issue: No ]
  • Positive And Negative Affect Schedule (PANAS) [ Time Frame: up to 14 weeks ] [ Designated as safety issue: No ]
  • Brief Patient Health Questionnaire (PHQ-9) [ Time Frame: up to 14 weeks ] [ Designated as safety issue: No ]
  • Multidimensional Pain Inventory Life Interference subscale (MPI-LIS) [ Time Frame: up to 14 weeks ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: July 2007
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Modified-release morphine then Placebo
up to a ceiling dose of 120 mg
Drug: Modified-release morphine
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 Name: Modified-release morphine sulfate
Drug: Placebo
Placebo Comparator: Placebo then modified-release morphine
Matching placebo
Drug: Modified-release morphine
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 Name: Modified-release morphine sulfate
Drug: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 - 65
  • Diagnosis of traumatic spinal cord injury
  • Neuropathic pain (pain related to the nervous system) rated at least 4 on a 11-point numeric rating scale at the time of screening
  • Pain classified as at level radicular pain (ALRP), at level central pain (ALCP) or below level central pain (BLCP).
  • Pain that is present regularly for at least 3 months prior to enrollment, in spite of medication or other pain treatment. This pain can be paroxysmal in nature (attacks of pain).
  • Ability to understand instructions and reliably provide pain assessments
  • Willingness to stop current opioid medications, if any
  • If a female with childbearing potential, using an approved method of birth control (intrauterine device (IUD), barrier protection, a contraceptive implantation system or injection (Norplant® or Depo-Provera®), oral contraceptive pills, or celibacy)

Exclusion Criteria:

  • A known sensitivity to opioids
  • A history of substance or alcohol abuse within the past 2 years
  • A need for elective surgery involving preoperative or postoperative analgesics or anesthetics during the study period
  • Other chronic pain that cannot be differentiated from ALCP, ALRP, or BLCP
  • A history of active cancer, excluding basal carcinoma of the skin, in the past 3 years
  • Serum creatinine levels >= 2.5 mg/dl or hepatic (liver) dysfunction with serum ALT, AST, GGT, or total bilirubin >= 3 times the upper limit of normal
  • Participation in any drug study in the last three months
  • Currently pregnant or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00488969

Locations
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
U.S. Department of Education
Investigators
Principal Investigator: Thomas Bryce, MD Icahn School of Medicine at Mount Sinai
  More Information

Responsible Party: Thomas N. Bryce, MD, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT00488969     History of Changes
Other Study ID Numbers: H133N060027  GCO # 90-135 
Study First Received: June 19, 2007
Last Updated: March 18, 2016
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Icahn School of Medicine at Mount Sinai:
Morphine
Chronic Pain
Spinal Cord Injury
Neuropathic Pain

Additional relevant MeSH terms:
Wounds and Injuries
Neuralgia
Spinal Cord Injuries
Pain
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Trauma, Nervous System
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 30, 2016