Methadone in Neuropathic Pain

Study Overview
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Brief Summary
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INTRODUCTION: There is an important need for inexpensive drugs that treat neuropathic pain. Early research suggests that methadone may be a good, inexpensive drug to treat neuropathic pain. Methadone is available in a low cost powder that is easily prepared for different routes of administration. This study will look at the effect and safety of methadone compared to the regular treatment of morphine for the treatment of chronic neuropathic pain. OBJECTIVES: First the investigators want to determine if methadone is effective and safe for the treatment of neuropathic pain. Since a placebo control group would be unethical, the proposed comparator will consist of the gold standard conventional treatment, controlled release morphine. The investigators will compare methadone to controlled-release morphine with regard to how it affects the level of pain and extent of side effects. Next the investigators want to examine safety as well as to determine whether methadone leads to improvements in physical and emotional functioning, and participants' satisfaction with the treatment. METHODS: A double blind, randomized trial comparing methadone and controlled release morphine is proposed. After 1-week, participants will be randomly assigned to either methadone or controlled release morphine and will gradually build to a dose at which they receive adequate pain relief without unacceptable levels of side effects. This 5-week phase will be followed by a 6-week dose phase and then a 4-week tapering off phase. Study drug: The study drug is methadone supplied in 2.5 mg tablets. The comparator will consist of controlled release morphine in 10 mg tablets. The dose of each will range from 1-12 tablets taken every 12 hours (dose ranges methadone 5-60 mg/day, controlled release morphine 20-240 mg/day). Setting: This is a 3-site study involving pain clinics in Halifax, Nova Scotia; London, Ontario; and Calgary, Alberta.

Conditions
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Chronic Neuropathic Pain

Intervention / Treatment
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* Drug: Methadone
* Drug: Controlled Release Morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than18 years Chronic neuropathic pain of central or peripheral origin for 3 months or longer as determined by the study physician and a score of 4/10 or greater on the DN4 Moderate to severe pain as defined by average 7-day pain score of greater than 4 on an 11-point numerical rating scale for pain intensity (NRS-PI). Physician has identified that an opioid is a valid adjunctive treatment for the chronic neuropathic pain. Concomitant non-opioid analgesic medications must have been stable for 14 days. Co-interventions such as TENS, acupuncture and massage must have been stable for 14 days prior to the trial If taking an opioid, maximum dose of opioid in oral morphine equivalents (OME) is 90 mg/24 hours. Ability to follow the protocol with reference to cognitive and situational conditions; e.g., stable housing, able to attend follow-up visits. Willing and able to give written informed consent. Exclusion Criteria: Patients on a dose of opioid that exceeds 90 mg/24 hours in OME Pregnant or lactating women (women of childbearing potential must have negative pregnancy test) History of psychosis History of (within the past 2 years) , or current, substance dependency disorder Excluded medications are listed in Appendix 1. Presence of clinically significant cardiac or pulmonary disorder on physical exam that would compromise participants' safety in the trial as judged by the study physician. Presence of significant conduction delay, ischemia or arrhythmia on screening ECG Presence of severe pain disorder other than the chronic neuropathic pain under study that would interfere with patient's ability to determine effect of study treatment on the chronic neuropathic pain Abnormalities above 1.5 times upper range of normal on screening CBC, blood chemistry including BUN, Cr, LDH, AST, ALT Patients with a history of allergy to any opioid. Participation in another clinical trial in the 30 days prior to enrolment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methadone<br> | Drug: Methadone<br>* Patients in the methadone arm will be supplied with 2.5 mg tablets. The dose will consist of 1-12 tablets taken twice daily, every 12 hours (range 5-60 mg per 24 hours).<br>|
| Active Comparator: Controlled Release Morphine<br>Controlled release morphine supplied in 10 mg tablets, 1-12 tablets taken twice daily, every 12 hours (range 20-240 mg per 24 hours). | Drug: Controlled Release Morphine<br>* controlled release morphine supplied in 10 mg tablets, 1-12 tablets taken twice daily, every 12 hours (range 20-240 mg per 24 hours).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to determine if methadone is an effective opioid for the treatment of chronic neuropathic pain |  | 16 weeks |