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

## TL;DR

A study tested a magnetic field device for treating chemotherapy-related nerve pain but found no significant pain relief, though motor function improved in some patients.

## Contribution

The study is the first to evaluate a non-pharmacological magnetic field device for persistent chemotherapy-induced peripheral neuropathy.

## Key findings

- No significant difference in pain reduction between the magnetic field device and sham device.
- Motor function improved significantly in patients using the magnetic field device.
- Improvements were more pronounced in patients who had completed chemotherapy over a year ago.

## Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxanes and platinum-based agents. We conducted a randomized, double-blind, sham-controlled, multicenter phase II study to evaluate the efficacy and safety of AT-04 in patients with persistent CIPN. Participants used devices for 12 weeks. Twenty-eight patients were randomized. For the primary endpoint, no significant difference was observed in pain NRS on day 85 {AT-04: −1.74 ± 0.6 vs. sham: −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 ended >1 year earlier (n = 16), CIPN motor scores improved from day 29 to day 85. No treatment-related adverse events occurred in the AT-04 group. AT-04 may be a promising non-pharmacological option; larger confirmatory trials are required.

Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.