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

Active sham Clinical trial Device Motor fluctuations OFF period OFF time Parkinson's Treatment Wearing off

Journal

Parkinsonism & related disorders
ISSN: 1873-5126
Titre abrégé: Parkinsonism Relat Disord
Pays: England
ID NLM: 9513583

Informations de publication

Date de publication:
27 Dec 2023
Historique:
received: 25 09 2023
revised: 09 12 2023
accepted: 10 12 2023
medline: 22 1 2024
pubmed: 22 1 2024
entrez: 21 1 2024
Statut: aheadofprint

Résumé

Studies have suggested that intrinsic auricular muscle zones (IAMZ) stimulation alleviates motor features of Parkinson disease (PD). 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. 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. 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.

Sections du résumé

BACKGROUND BACKGROUND
Studies have suggested that intrinsic auricular muscle zones (IAMZ) stimulation alleviates motor features of Parkinson disease (PD).
METHODS 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 38246833
pii: S1353-8020(23)01038-6
doi: 10.1016/j.parkreldis.2023.105959
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

105959

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The study was funded by Stoparkinson, LLC, makers of the EARSTIM device.

Auteurs

Hubert H Fernandez (HH)

Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, USA. Electronic address: fernanh@ccf.org.

Eric A Macklin (EA)

Department of Neurology, Harvard Medical School/Massachusetts General Hospital, USA.

Robert A Hauser (RA)

Department of Neurology, University of South Florida School of Medicine, USA.

Kelvin L Chou (KL)

Department of Neurology, University of Michigan School of Medicine, USA.

Yusuf O Cakmak (YO)

Stoparkinson Healthcare Systems, LLC, USA.

Burak Ozsoy (B)

Stoparkinson Healthcare Systems, LLC, USA.

Stanley Fahn (S)

Department of Neurology, Columbia University School of Medicine, USA.

Classifications MeSH