- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00488969
Effectiveness of Controlled-Release Morphine for Chronic Neuropathic Pain After Spinal Cord Injury
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New York
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New York, New York, United States, 10029
- Mount Sinai School of Medicine
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Modified-release morphine then Placebo
up to a ceiling dose of 120 mg
|
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 Names:
|
Placebo Comparator: Placebo then modified-release morphine
Matching placebo
|
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pain severity
Time Frame: Average of daily ratings over 14 days
|
Pain severity rated using a 0-10 Numeric Rating Scale (NRS)
|
Average of daily ratings over 14 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Short McGill Pain Questionnaire (modified) (SF-McGill)
Time Frame: up to 14 weeks
|
up to 14 weeks
|
|
Opioids cognitive effects scale
Time Frame: up to 14 weeks
|
up to 14 weeks
|
|
Patient Generated Index for activity (PGI)
Time Frame: up to 14 weeks
|
up to 14 weeks
|
|
Daily number of attacks of paroxysmal pain
Time Frame: up to 14 weeks
|
up to 14 weeks
|
|
Quantitative sensory testing
Time Frame: up to 14 weeks
|
Allodynia, hyperalgesia, and temporal summation (determined using quantitative sensory testing)
|
up to 14 weeks
|
Subject global impression of change
Time Frame: up to 14 weeks
|
up to 14 weeks
|
|
Short-Form 36 (SF-36)
Time Frame: up to 14 weeks
|
up to 14 weeks
|
|
Positive And Negative Affect Schedule (PANAS)
Time Frame: up to 14 weeks
|
up to 14 weeks
|
|
Brief Patient Health Questionnaire (PHQ-9)
Time Frame: up to 14 weeks
|
up to 14 weeks
|
|
Multidimensional Pain Inventory Life Interference subscale (MPI-LIS)
Time Frame: up to 14 weeks
|
up to 14 weeks
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Central Nervous System Diseases
- Nervous System Diseases
- Pain
- Neurologic Manifestations
- Neuromuscular Diseases
- Peripheral Nervous System Diseases
- Trauma, Nervous System
- Spinal Cord Diseases
- Neuralgia
- Wounds and Injuries
- Spinal Cord Injuries
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Opioid
- Narcotics
- Morphine
Other Study ID Numbers
- H133N060027
- GCO # 90-135
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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