Methadone + Duloxetine for Peripheral Neuropathy
(METACIN Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: University of British Columbia

No Placebo Group

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

Chemotherapy induced peripheral neuropathy (CIPN) or nerve pain, is a painful and debilitating complication which can chronically affect up to 70% of patients who receive chemotherapy. It causes "glove-and-stocking" distribution of nerve-pain, weakness, and other debilitating symptoms. This can affect patient's quality of life, function, ability to tolerate chemotherapy, and return to work. Duloxetine is the only recommended medication to reduce the painful symptoms and consequences of CIPN by national and international groups such as the American Society of Clinical Oncology. However, studies indicate it only has modest effect; for example, the largest study shows it only reduces pain by 0.73/10 points compared to placebo. Another promising medication in theory and practice is methadone. It is a commonly used and well-studied opioid with unique attributes which allows it to treat non-cancer and cancer associated nerve-pain with better efficacy when compared to other opioids. Furthermore, patients appear to develop less tolerance to methadone over time when compared to other opioids; this is helpful as many develop long-term CIPN and may greatly benefit from long-term pain medication. Therefore, if a patient requires chronic opioids to reduce the painful symptoms of CIPN, one that develops less tolerance is invaluable. Despite the promising role for methadone to treat CIPN, it has not been studied to treat this condition. Therefore, methadone may never be considered by prescribers to reduce the painful symptoms of CIPN. This study is a randomized controlled trial to assess the efficacy of methadone compared to duloxetine to treat painful CIPN. Participants will be randomized to receive either methadone or duloxetine regularly for 5 weeks. Methadone and duloxetine will be placed in indistinguishable capsules, so the participant and assessor are not aware of their treatment. They will be followed virtually or in-person weekly for 5 weeks where they will answer brief questionnaires detailing the effect of their treatment on their pain and their dose will increase weekly as tolerated until their pain is controlled or its the end of the study. This study would be critical in assessing the efficacy of a very promising medication to reduce the painful symptoms of CIPN: a debilitating disorder with otherwise few treatment options.

Research Team

Eligibility Criteria

This trial is for adults over 18 with a life expectancy greater than 12 weeks, experiencing moderate to severe nerve pain from chemotherapy (CIPN) lasting more than 3 months after treatment. They must have had cancer treated with specific chemotherapies and be new to opioids or on low doses. Stable use of other pain medications for at least two weeks is required.

Inclusion Criteria

My doctor expects me to live more than 12 weeks.

I am older than 18 years.

I either don't use opioids or take less than 60 mg of morphine a day.

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Treatment Details

Interventions

Methadone (Opioid)

Trial OverviewThe study compares methadone and duloxetine's effectiveness in treating CIPN. Participants will randomly receive either drug in identical capsules, unaware of which one they're taking, and report their pain weekly for five weeks while the dose may increase until pain relief or study end.

Participant Groups

2Treatment groups

Experimental Treatment

Active Control

Group I: methadoneExperimental Treatment1 Intervention

Methadone is a strong opioid that is μ-opioid receptor agonist like other opioids; however, it is additionally a N-methyl-D- aspartate antagonist with serotonin and norepinephrine reuptake inhibition; these attributes enable its efficacy in neuropathic pain and may prevent opioid tolerance over time. It is commonly used to treat opioid use disorder, as well as to treat severe pain. This medication is taken orally every 8 hours when used to treat pain. It has not been studied to treat chemotherapy-induced peripheral neuropathy.

Group II: duloxetineActive Control1 Intervention

Duloxetine is a serotonin and norepinephrine reuptake inhibitor that is commonly used to treat major depressive disorder, generalized anxiety disorder, and neuropathic pain. This medication is taken orally once daily for all of its indications. It is the only well-studied medication that is recommended internationally to treat chemotherapy-induced peripheral neuropathy.

Methadone is already approved in Canada, Japan, Switzerland for the following indications: