NCT05786599 Methadone to Treat Painful Chemotherapy Induced Peripheral Neuropathy

Eligibility & Interventions

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What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.

This trial targets 50 participants in total. It began in 2025-03-21 with a primary completion date of 2026-03.

Brief 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.

Eligibility Criteria

Inclusion Criteria: 1. Age \>18 years old. 2. Estimated life expectancy greater than 12 weeks. 3. Opioid naïve or oral morphine equivalent use \<60 mg/day. 4. Greater than grade 1 CIPN based on CTCAE. 5. \>3/10 average CIPN-related neuropathic pain lasting ≥3 months beyond chemotherapy completion. 6. A cancer diagnosis. 7. Treatment with one of the following neurotoxic chemotherapies: platinums, taxanes, vinca alkaloids, bortezomib, or thalidomide. Exclusion Criteria: 1. Other causes of peripheral neuropathy. 2. The following psychiatric illnesses: severe depression, suicidality, bipolar disease or psychotic disorder, alcohol or substance use disorder, DSM V criteria eating disorder. 3. The following medical illnesses: known or suspected mechanical gastrointestinal obstruction or any disease/conditions that affect bowel transit, suspected surgical abdomen, acute or severe asthma, COPD, acute respiratory depression, elevated serum CO2 and cor pulmonale, delirium tremens, convulsive disorders, severe CNS depression such as from cerebrospinal or intracranial pressure and head injury, diarrhea from pseudomembranous colitis, leptomeningeal disease. 4. Liver or renal dysfunction within the last 90 days as defined by MELD-Na score ≥17 and GFR ≤30 ml/min respectively. 5. QTC \>499ms within last 90 days. 6. Current pregnancy or lactation. 7. Inability to take oral medications. 8. Positive CAGE and/or Opioid Risk Tool - Revised questionnaire 9. Known allergy or hypersensitivity to opioids, duloxetine, or any ingredient in their formulation. 10. Concomitant use of excluded medications: methadone, other antidepressants (including within 14 days of discontinuing monoamine oxidase inhibitors), thioridazine, potent CYP1A2 inhibitors (such as fluvoxamine and some quinolone antibiotics). 11. Uncontrolled narrow-angle glaucoma. 12. If women of child-bearing potential (i.e. Menstruation within \<2 years) are unable or unwilling to use Health Canada approved highly effective methods of contraception (hormonal contraceptives, intrauterine device or system, vasectomy, tubal ligation, or double barrier method), or abstinence during the treatment period. Note: Any use of prior co-analgesics will be continued (and must have been stable for more than 2 weeks), but the use of new co-analgesics or titration of current co-analgesics will not be permitted during the trial.

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