Randomized Controlled Trial to Relieve Pain of Chemotherapy-Induced Peripheral Neuropathy by Magnetic Field: SMILE...

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxanes and platinum-based agents, impairing quality of life. Duloxetine is the only drug with proven efficacy, but is often limited by tolerability. AT-04 is a portable alternating magnetic field device that activates descending pain modulatory systems and has shown safety in other pain settings. This investigator-initiated trial evaluated the efficacy and safety of AT-04 for persistent CIPN.

We conducted a randomized, double-blind, sham-controlled, multicenter phase II study. Patients with CIPN lasting ≥12 weeks after chemotherapy and pain NRS ≥ 4 were enrolled. Participants used AT-04 or sham devices twice daily for 12 weeks. The primary endpoint was the change in pain NRS on day 85. Secondary endpoints included tingling NRS, numbness NRS, CIPN20 subscales, and safety.

Twenty-eight patients were randomized (14 per arm). No significant difference was observed in pain NRS on day 85 {AT-04: -1.74 ± 0.6 vs. sham device: -1.45 ± 0.6; one-sided p = 0.36, effect size (ES) = 0.48}. CIPN20 motor scores improved with AT-04 on days 29 (-9.82 ± 13.8 vs. 0.74 ± 8.7, respectively; p = 0.035, ES = 0.92) and 57 (-11.81 ± 10.6 vs. -0.54 ± 6.7, respectively; p < 0.01, ES = 1.26). Among patients whose last chemotherapy had ended >1 year earlier (n = 16), motor scores improved from days 29 (-12.43 ± 10.3 vs. 2.38 ± 8.9, respectively; p < 0.01, ES = 1.55) to 85 (-11.76 ± 10.1 vs. -0.07 ± 11.5, respectively; p = 0.049, ES = 1.08), while sensory/autonomic scales showed trends. No treatment-related adverse events occurred in the AT-04 group.

AT-04 did not significantly reduce pain NRS but improved motor function in CIPN patients, especially in those >1 year after chemotherapy. AT-04 may be a promising non-pharmacological option; larger confirmatory trials are required.