Methadone to Treat Painful Chemotherapy Induced Peripheral Neuropathy

Summary

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.

Conditions

• Chemotherapy-induced Peripheral Neuropathy

Interventions

DRUG

methadone

The treatment arm will take methadone 2 mg PO q8h and a placebo called "placeboD" PO qdaily. PlaceboD and duloxetine will be placed in capsules to be virtually indistinguishable. Participants will be followed (televisit or in-person) by assessors every week; this will take approximately 15 minutes. This includes review of questionnaire(s), adverse events (and any potential management), and recommendations on dose titration. To maintain blinding and ensure standardization across assessors, titration protocols will be provided. If pain is not controlled, the assessors will instruct the participant to increase their methadone/placeboM drug by 1 capsule PO q8h and their duloxetine/placeboD drug to 2 capsules PO qdaily (the study maximum). If there are poorly tolerated adverse events the dose will be reduced to the previously tolerated dose, and then the following week they may attempt to titrate up again per the above protocol.

DRUG

duloxetine

The control arm will receive duloxetine 30 mg PO qdaily, and a placebo called "placeboM" PO q8h. PlaceboM and methadone will be placed in capsules to be virtually indistinguishable. Participants will be followed (televisit or in-person) by assessors every week; this will take approximately 15 minutes. This includes review of questionnaire(s), adverse events (and any potential management), and recommendations on dose titration. To maintain blinding and ensure standardization across assessors, titration protocols will be provided. If pain is not controlled, the assessors will instruct the participant to increase their methadone/placeboM drug by 1 capsule PO q8h and their duloxetine/placeboD drug to 2 capsules PO qdaily (the study maximum). If there are poorly tolerated adverse events the dose will be reduced to the previously tolerated dose, and then the following week they may attempt to titrate up again per the above protocol.

Sponsors & Collaborators

• British Columbia Cancer Agency

  collaborator OTHER

• University of British Columbia

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

19 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-03-21

Primary Completion

2026-03-31

Completion

2026-03-31

Countries

• Canada

Study Locations