Intrinsic auricular muscle zone stimulation for Parkinson disease: The EARSTIM-PD Phase II multi-center pilot study results.

BACKGROUND:Studies have suggested that intrinsic auricular muscle zones (IAMZ) stimulation alleviates motor features of Parkinson disease (PD). METHODS:A randomized, blinded, active sham-controlled pilot trial was conducted to evaluate the safety and dose-response-time curve of Earstim using a 3-treatment, 3-period crossover design in PD patients experiencing OFF time on levodopa. Treatments were: short (20-min) IAMZ stimulation; long (60-min) IAMZ stimulation; and 20-min active sham stimulation of non-muscular areas. Assessment time points were: prior to treatment, and 20, 40, 60, 90, and 120 min after treatment onset. Primary safety endpoints were adverse events frequency and severity. Primary efficacy endpoint was the change in MDS-UPDRS motor score at 20 min after treatment onset in the IAMZ treatment groups versus sham. RESULTS:Forty-six individuals consented; 38 were randomized (average age 64 years, 65 % male, mean 8.2 years from diagnosis). No serious adverse events or significant device-related events occurred. At 20 min after treatment onset, motor improvements did not differ between IAMZ treatments versus sham. However, at 60 min after treatment onset, motor improvement peaked on IAMZ treatments compared to sham (difference: 3.1 [-5.9 to 0.3], p = 0.03). While the difference in 120-min AUC change between IAMZ treatments versus sham was not significant, the short-stimulation IAMZ treatment showed the largest aggregate motor score improvement (AUC = -456 points, 95 % CI -691 to -221) compared to sham. CONCLUSION:Earstim was well-tolerated. The greatest motor improvement occurred at 60 min after stimulation onset in the short-stimulation IAMZ treatment, and supports its further study to alleviate OFF periods.