Auricular Muscle Zone Stimulation for Parkinson Disease (Earstim-PD)

Auricular Muscle Zone Stimulation for Parkinson Disease (Earstim-PD)

A Multicenter, Randomized, Blinded, Electronic Device in Subjects with Parkison Disease.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: Earstim - Active Stimulation; Device: Earstim - Sham Stimulation

Detailed Description

This study is a multi-center, prospective, randomized, double-blinded, sham-controlled, within-subject design, 3-treatment, 3-period cross-over study involving 38 subjects with Parkinson's Disease who have the wearing-off phenomenon on oral levodopa therapy. All participants will receive three treatments on different days, each with different stimulation conditions. All subjects will wear the Earstim device on the ear ipsilateral to the side of the body more affected by Parkinson's Disease for 120 minutes during each of the three treatment applications.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorder's Center, PC
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson Disease and Movement Disorder Center of Boca Raton
    • Gainesville, Florida, United States, 32608
      • University of Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas
  • Washington
    • Kirkland, Washington, United States, 98034
      • Booth Gardner Parkinson's Care Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject is a male or female ≥18 years of age.
2. Subject has Parkinson's Disease and is on levodopa therapy.
3. Subject experiences OFF periods with an "ON" score ≥20% better than the OFF score as measured by the MDS-UPDRS motor score (MDS-UPDRS Part III).
4. The subject's daily "OFF" time duration is ≥2 hours per day.
5. The subject's Hoehn-Yahr stage when "OFF" must be less than Stage 4 (i.e., subject must be able to walk without the use of an assisted device, such as a cane or a walker).
6. Subject receives levodopa at least TID with a minimum of 100 mg levodopa administered with each dose.
7. Subject can tolerate 2 hours in an "OFF" period without requiring rescue medication.
8. Subject is willing and able to not change Parkinson's Disease medications or dosages during the up to 2 week study therapy period.
9. Subject is willing to provide Informed Consent to participate in the study.
10. Subject is willing and able to comply with all study procedures and required availability for study visits.

Exclusion Criteria:

1. Subject has a medical or psychiatric comorbidity that can compromise participation in the study.
2. Subject has cognitive dysfunction defined by a Montreal Cognitive Assessment (MoCA) score <24.
3. Subject has moderate levodopa-induced dyskinesias as indicated by a score >2 on items 4.1 and/or 4.2 in the MDS-UPDRS Part IV.
4. Subject has clinically significant depression as determined by the Beck Depression Inventory-II score >15.
5. Subject is pregnant as determined by a urine pregnancy test at the screening visit.
6. Subject is of childbearing potential and is not surgically sterilized or does not use a reliable measure of contraception.
7. Subject has a form of Parkinsonism other than Parkinson's Disease, such as Drug-induced Parkinsonism or Multiple System Atrophy.
8. Subject has an implanted deep brain stimulator (DBS).
9. Subject is receiving direct intestinal infusions of levodopa.
10. Subject has epilepsy.
11. Subject medications are anticipated to change during the two (2) week study period (Note: the study requires stable medications during the device testing period).
12. Subject has a cardiac pacemaker or defibrillator, bladder stimulator, spinal cord stimulator or other active electronic medical device.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active Stimulation 20 minutes; Intramuscular stimulation	Device: Earstim - Active Stimulation; Intramuscular stimulation
ACTIVE_COMPARATOR: Active Stimulation 60 minutes; Intramuscular stimulation	Device: Earstim - Active Stimulation; Intramuscular stimulation
SHAM_COMPARATOR: Sham Stimulation 20 minutes; Muscle-free-zone stimulation	Device: Earstim - Sham Stimulation; Sham stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Score) at 20 minutes	The primary efficacy endpoint is the overall change from baseline to 20 minutes after onset of stimulation in MDS-UPDRS motor score (MDS-UPDRS Part III), comparing the sham arm vs the average 20-minute change of the 20-minute and 60-minute auricular stimulation. Each parkinsonian sign or symptom is rated on a 5-point Likert-type scale (ranging from 0 to 4), with higher scores indicating more severe impairment.	Baseline, 20 minutes after the stimulation is initiated

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Curve	The area under the curve (AUC) of change from prior to stimulation in MDS-UPDRS Part III total motor score over the entire 120 minute post-stimulation follow-up interval, comparing the sham treatment to the 20 and 60 minute treatments with auricular muscle zone stimulation by subject and by treatment group.	120 minutes after stimulation is initiated.
Maximal improvement in MDS-UPDRS motor score (MDS-UPDRS Part III) from prior to stimulation to any of the follow-up time points up to 120 minutes after onset of stimulation.	Maximal improvement in MDS-UPDRS motor score (MDS-UPDRS Part III) from prior to stimulation to any of the follow-up time points (20 ,40, 60, 90, and 120 minutes after onset of stimulation). Each parkinsonian sign or symptom is rated on a 5-point Likert-type scale (ranging from 0 to 4), with higher scores indicating more severe impairment	120 minutes after stimulation is initiated.
Patient Global Impression of Change (PGIC) scored by the subject prior to stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Patient Global Impression of Change (PGIC) scored by the subject prior to stimulation and at the follow-up time points (20,40, 60, 90, and 120 minutes after onset of stimulation). Seven point Likert scale ranging from 1= much worse to 7= much better	120 minutes after stimulation is initiated.
Timed Get Up and Go test prior to stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Timed Get Up and Go test prior to stimulation and at the follow-up time points (20 ,40, 60, 90, and 120 minutes after onset of stimulation).	120 minutes after stimulation is initiated.
Clinical Global Impression of Change (CGIC) prior to stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Clinical Global Impression of Change (CGIC) prior to stimulation and at the follow-up time points (20 ,40, 60, 90, and 120 minutes after onset of stimulation). Seven point Likert scale ranging from 1= much worse to 7= much better	Baseline, 120 minutes after stimulation is initiated.
Kinesia-ONE™ Variable: Finger Tapping Speed Score comparison between the three different treatments at the specified times of just before stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Kinesia-ONE scores ranged from 0 to 4 (where 0 is normal and 4 represents severe abnormalities), with negative change from Baseline scores indicating improvement in disease symptoms.	120 minutes after stimulation is initiated.
Kinesia-ONE™ Variable: Rest Tremor Score comparison between the three different treatments at the specified times of just before stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Kinesia-ONE scores ranged from 0 to 4 (where 0 is normal and 4 represents severe abnormalities), with negative change from Baseline scores indicating improvement in disease symptoms.	120 minutes after stimulation is initiated.
Kinesia-ONE™ Variable: Averaged Finger Tapping Speed and Resting Tremor Scores comparison between each study arm at the specified times of just before stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	The finger tapping speed scores and resting tremor scores were averaged and provided as one score ranging from 0 to 4 (where 0 is normal and 4 represents severe abnormalities), with negative change from Baseline scores indicating improvement in disease symptoms.	120 minutes after stimulation is initiated.
Kinesia-ONE™ Variable: Postural Tremor Score comparison between the three different treatments at the specified times of just before stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Kinesia-ONE scores ranged from 0 to 4 (where 0 is normal and 4 represents severe abnormalities), with negative change from Baseline scores indicating improvement in disease symptoms.	120 minutes after stimulation is initiated.
Kinesia-ONE™ Variable: Finger Tapping Amplitude Score comparison between the three different treatments at the specified times of just before stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Kinesia-ONE scores ranged from 0 to 4 (where 0 is normal and 4 represents severe abnormalities), with negative change from Baseline scores indicating improvement in disease symptoms.	120 minutes after stimulation is initiated.
Kinesia-ONE™ Variable: Hand Grasp Speed Score comparison between the three different treatments at the specified times of just before stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Kinesia-ONE scores ranged from 0 to 4 (where 0 is normal and 4 represents severe abnormalities), with negative change from Baseline scores indicating improvement in disease symptoms.	120 minutes after stimulation is initiated.
Kinesia-ONE™ Variable: Hand Grasp Amplitude Score comparison between the three different treatments at the specified times of just before stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Kinesia-ONE scores ranged from 0 to 4 (where 0 is normal and 4 represents severe abnormalities), with negative change from Baseline scores indicating improvement in disease symptoms.	120 minutes after stimulation is initiated.
Kinesia-ONE™ Variable: Rapid Alternating Movement Speed Score comparison between the three different treatments at the specified times of just before stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Kinesia-ONE scores ranged from 0 to 4 (where 0 is normal and 4 represents severe abnormalities), with negative change from Baseline scores indicating improvement in disease symptoms.	120 minutes after stimulation is initiated.
Kinesia-ONE™ Variable: Rapid Alternating Amplitude Score comparison between the three different treatments at the specified times of just before stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Kinesia-ONE scores ranged from 0 to 4 (where 0 is normal and 4 represents severe abnormalities), with negative change from Baseline scores indicating improvement in disease symptoms.	120 minutes after stimulation is initiated.
Kinesia-ONE™ Variable: Dyskinesia Score comparison between the three different treatments at the specified times of just before stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Kinesia-ONE scores ranged from 0 to 4 (where 0 is normal and 4 represents severe abnormalities), with negative change from Baseline scores indicating improvement in disease symptoms.	120 minutes after stimulation is initiated.
Determination by the investigator of dyskinesia severity by MDS-UPDRS Part IV prior to stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Determination by the investigator of dyskinesia severity by MDS-UPDRS Part IV prior to stimulation and at the follow-up time points (20 ,40, 60, 90, and 120 minutes after onset of stimulation). dyskinesia severity is rated on a 5-point Likert-type scale (ranging from 0 to 4), with higher scores indicating more severe impairment	120 minutes after stimulation is initiated
Determination by a consensus between subject and investigator of whether the subject is "OFF" or "ON" prior to stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Determination by a consensus between subject and investigator of whether the subject is "OFF" or "ON" prior to stimulation and at the follow-up time points (20 ,40, 60, 90, and 120 minutes after onset of stimulation).	120 minutes after stimulation is initiated.
Change in mood as measured by the Depressed Mood Score from baseline to 120 minutes after onset of stimulation.	Change in mood as measured by the Depressed Mood Score in Part I of MDS-UPDRS from pre-stimulation to 120 minutes after onset of stimulation.	120 minutes after stimulation is initiated.
Change in mood as measured by the Anxiety Mood Score from baseline to 120 minutes after onset of stimulation.	Change in mood as measured by the Anxiety Mood Score in Part I of MDS-UPDRS from pre-stimulation to 120 minutes after onset of stimulation.	120 minutes after stimulation is initiated.
Change in subjects' sense of well-being as measured by an exploratory ordinal scale prior to stimulation and at the follow-up time points up to 120 minutes after onset of stimulation.	Change in subjects' sense of well-being as measured by an exploratory ordinal scale prior to stimulation and at the follow-up time points (20 ,40, 60, 90, and 120 minutes after onset of stimulation). Scores ranged from +3 to -3 (+3 represents more comfortable - much greater peace of mind; and -3 represents more uncomfortable and have a much greater worse peace of mind	120 minutes after stimulation is initiated.

Collaborators and Investigators

• Sponsor: Stoparkinson Healthcare Systems LLC
• Collaborators: The Parkinson Study Group
• Investigators: Study Director: Yusuf O Cakmak, MD, PhD, Stoparkinson Healthcare Systems LLC; Principal Investigator: Stanley Fahn, MD, H. Houston Merritt Professor of Neurology, Columbia University Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2021
• Primary Completion (ACTUAL): January 5, 2022
• Study Completion (ACTUAL): January 5, 2022

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (ACTUAL): December 3, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 7, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: STP-PD-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes