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

NCT ID: NCT00488969

Last Updated: 2016-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2013-07-31

Brief 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.

Conditions

Neuropathic Pain; Spinal Cord Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Modified-release morphine then Placebo

up to a ceiling dose of 120 mg

Group Type: ACTIVE_COMPARATOR

Modified-release morphine

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

Placebo then modified-release morphine

Matching placebo

Group Type: PLACEBO_COMPARATOR

Modified-release morphine

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

Interventions

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.

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Modified-release morphine sulfate

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

U.S. Department of Education

FED

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Thomas N. Bryce

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas Bryce, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai School of Medicine

New York, New York, United States

Countries

United States

Other Identifiers

GCO # 90-135

Identifier Type: -

Identifier Source: secondary_id

H133N060027

Identifier Type: -

Identifier Source: org_study_id