EarStim for short- and long-term relief of Parkinson's motor symptoms

Multicenter Study of Safety and Effectiveness of Auricular Muscle Zone Stimulation With the EarStim Novel Device for Parkinson's Disease

This study tests whether a wearable EarStim device can give intermittent short- and long-term relief of motor symptoms in adults with moderate-to-severe Parkinson's disease who experience wearing-off.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 44 Years and up
• Sex: All
• Sponsor: Stoparkinson Healthcare Systems LLC (Industry-sponsored)
• Locations: 2 sites (Istanbul and 1 other locations)
• Trial ID: NCT07400731 on ClinicalTrials.gov

What this trial studies

This prospective, multicenter study enrolls adults with moderate-to-severe Parkinson's disease on stable carbidopa/levodopa who experience ON/OFF wearing-off. Period A is a randomized, double-blind, sham-controlled in-clinic phase comparing EarStim to a sham device for immediate motor effects. Period B is an unblinded, standard-of-care-controlled phase in which participants use the EarStim system at home for 90 days to evaluate longer-term effectiveness and safety. The device targets intrinsic auricular muscle zones (IAMZ) via non-invasive high-frequency stimulation to engage brainstem and basal ganglia motor pathways.

Who should consider this trial

Good fit: Ideal candidates are adults aged 44 or older with Parkinson's disease on stable carbidopa/levodopa, an MDS-UPDRS Part III score ≥33, documented ON/OFF wearing-off with at least a 20% improvement after medication, and willingness to avoid PD medication changes during the 90-day study.

Not a fit: Patients with mild PD who do not experience wearing-off, those with major cognitive impairment, implanted neurostimulators, or an inability to use or tolerate a wearable ear device are unlikely to benefit.

Why it matters

Potential benefit: If successful, EarStim could provide a non-invasive, on-demand option to reduce OFF motor symptoms between medication doses and potentially delay more invasive treatments.

How similar studies have performed: Small pilot studies of auricular and peripheral nerve stimulation, including IAMZ high-frequency stimulation, have reported symptomatic improvements, but large randomized evidence is limited.

Eligibility criteria

Inclusion Criteria:

Patients fulfilling the following criteria are eligible for participation:

* Subject must be ≥44 years of age.
* Subject has PD and is on stable carbidopa/levodopa therapy for at least four weeks prior to enrollment in the study.
* Subject must be willing and able to refrain from changing PD medications or dosages during the 90-day study.
* Subject reports experiencing both "ON" and "OFF" episodes (MDS-UPDRS Part IV - Time Spent in the OFF-state score ≥1), as assessed and determined by the investigator.

  \*This corresponds to item 4.3 in MDS-UPDRS Part IV, where a score of 0 (zero) indicates that the subject experiences no OFF periods during the waking day, and a score of ≥1 reflects the presence of OFF periods at any level.
* Subject experiences "OFF" periods with an "ON" score that is ≥20% better than the "OFF" score, as measured by the MDS-UPDRS Part III score, 1 hour after taking their dose of carbidopa/levodopa.
* Subject has an MDS-UPDRS Part III score ≥33 in "OFF" period.
* Subject agrees to remain in an "OFF" period for up to 3 hours without requiring rescue medication.
* Subject can walk independently, without the use of an assisted device (e.g., cane or walker), in both "ON" and "OFF" periods.
* Subject is willing to provide informed consent to participate in the study.
* Subject is willing and able to comply with all study procedures and required availability for study visits.

Exclusion Criteria:

Patients who meet any of the following criteria are to be excluded from participation:

* Subject has a medical or psychiatric comorbidity that may compromise participation in the study.
* Subject has a history of cardiac rhythm disorders (e.g., atrial fibrillation, ventricular tachycardia, or atrioventricular block).
* Subject is pregnant or planning to become pregnant during the course of the study.
* Subject has a form of Parkinsonism other than PD, such as drug-induced Parkinsonism or Multiple System Atrophy.
* Subject is currently using on-demand medications for PD, such as subcutaneous apomorphine, sublingual apomorphine, and levodopa inhalation powder.
* Subject has an implanted deep brain stimulator (DBS).
* Subject is receiving direct intestinal infusions of levodopa.
* Subject has a history of epilepsy.
* Subject's medications are expected to change during the 90-day study period.
* Subject has a cardiac pacemaker, defibrillator, bladder stimulator, spinal cord stimulator, or any other active electronic medical device.
* Subject is unable to understand or follow the instructions required by the study.
* Subject has an ear infection or skin condition around the ear.
* Subject is participating, or has participated, in another interventional clinical trial in the last 30 days that may confound the results of this study, unless approved by the Sponsor.
* Subject has a history of brain surgery or peripheral neuropathy.
* Subject is actively using TENS or has a history of chronic TENS use within the last 2 weeks prior to study enrollment.
* Subject consumed alcohol or caffeine within 12 hours of study enrollment or has a history of alcohol dependence

Where this trial is running

Istanbul and 1 other locations

• Koc University Hospital — Istanbul, Turkey (Türkiye) (Recruiting)
• Şişli Hamidiye Etfal Research and Training Hospital — Istanbul, Turkey (Türkiye) (Not_yet_recruiting)

Study contacts

• Study coordinator: Yusuf Özgür Çakmak, MD, PhD, Assoc.Prof

Conditions PARKINSON DISEASE; parkinson disease; intrinsic auricular muscle zone stimulation; IAMZ