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

Spinal Cord Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00488969
• Other study ID #: H133N060027
• Secondary ID: GCO # 90-135
• Status: Recruiting
• Phase: Phase 2
• First received: June 19, 2007
• Last updated: July 24, 2007
• Start date: July 2007

Study information

• Verified date: July 2007
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Anousheh Behnegar, MD
• Phone: 212-659-9379
• Email: Anousheh.Behnegar[@]mountsinai.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain
• Spinal Cord Injuries
• Spinal Cord Injury

Intervention

Drug:
• Modified-release morphine sulfate

Locations

Country	Name	City	State
United States	Mount Sinai School of Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	U.S. Department of Education

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain severity (rated using a 0-10 Numeric Rating Scale [NRS])		Average of daily ratings over 14 days
Secondary	Adverse Events		Daily
Secondary	Short McGill Pain Questionnaire (modified) (SF-McGill)		at randomization and at the midpoint of each 7-week drug or placebo period
Secondary	Opioids cognitive effects scale		at randomization and at the midpoint of each 7-week drug or placebo period
Secondary	Patient Generated Index for activity (PGI)		at randomization and at the midpoint of each 7-week drug or placebo period)
Secondary	Daily number of attacks of paroxysmal pain		Daily
Secondary	Allodynia, hyperalgesia, and temporal summation (determined using quantitative sensory testing)		at randomization and at the midpoint of each 7-week drug or placebo period)
Secondary	Concomitant medication usage		daily
Secondary	Subject global impression of change		two times during the 14 week study period (at the midpoint of each 7-week drug or placebo period
Secondary	Short-Form 36 (SF-36)		at randomization and at the midpoint of each 7-week drug or placebo period
Secondary	Positive And Negative Affect Schedule (PANAS)		at randomization and at the midpoint of each 7-week drug or placebo period
Secondary	Brief Patient Health Questionnaire (PHQ-9)		at randomization and at the midpoint of each 7-week drug or placebo period
Secondary	Multidimensional Pain Inventory Life Interference subscale (MPI-LIS)		at randomization and at the midpoint of each 7-week drug or placebo period
Secondary	Sleep interference assessment		at randomization and at the midpoint of each 7-week drug or placebo period
Secondary	Medication quantity effective for analgesia or maximally tolerated [Time Frame:		two times during the 14 week study period (at the midpoint of each 7-week drug or placebo period)]