High Frequency Light, Sound, and Tactile Stimulation to Improve Motor and Cognitive Deficits in Parkinson's Disease

Acute Treatment of Parkinson's Disease With Gamma Frequency Stimulation

Parkinson's disease (PD) impacts different types of neural oscillations in the brain, including beta (13-30Hz) and gamma oscillations (30-80Hz), which contributes to PD's cardinal symptoms of resting tremor, rigidity, bradykinesia (slowness of movement), and gait instability. The investigators' lab has developed a non-invasive method of increasing gamma power in the brain using Gamma Entrainment Using Sensory Stimulation (GENUS) through light, sound, and tactile stimulation devices. For this study, 40 participants with mild Parkinson's disease will be recruited, and the investigators will assess their brain waves with electroencephalogram (EEG) before, during, and after light, sound, and tactile stimulation to determine the safety, feasibility, and optimization of GENUS as a potential therapy in the PD population.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: GENUS device (Active Settings); Device: GENUS device (Sham settings)

Detailed Description

It is known that Parkinson's disease (PD) patients have disruptions in brain waves, specifically the beta frequency (13 - 30Hz) and gamma frequency (~30 - 100 Hz), due to the death of dopaminergic neurons in certain parts of the brain. These disruptions of brain rhythms contribute to the cardinal symptoms of Parkinson's (resting tremor, rigidity, bradykinesia or slowness of movement and gait stability) in different ways. The investigators' lab has developed a non-invasive method of neuromodulation called Gamma Entrainment Using Sensory Stimulation (GENUS), which could be used for patients suffering from motor symptoms due to PD. GENUS is administered via light, sound, and tactile stimulation devices which emit light, audio, and tactile frequencies respectively. GENUS has been tested on cognitively normal individuals and individuals with mild Alzheimer's Disease (AD), and the device was found to be safe for use and effective for entrainment in both populations.

Investigators hypothesize that boosting gamma oscillations using 40Hz GENUS will augment movement and improve tremor and bradykinesia in PD patients. Thus, the purpose of this study is to determine whether gamma entrainment through non-invasive 40Hz sensory stimulation can be observed in patients with PD as measured by electroencephalogram (EEG) during an acute stimulation session. Investigators also hope to determine whether the GENUS devices are safe and easy to use in the PD population.

The investigators will recruit 40 participants diagnosed with mild PD who will be randomly assigned to two study arms: control stimulation and active 40Hz stimulation. Participants will be asked to do a series of movement exercises while wearing an actigraphy watch that tracks their activity before the stimulation session. Cognitive and mental health evaluations and memory tests will also be performed on all participants before and after exposure to the GENUS devices, which can deliver light, sound, and tactile waves at different frequencies. The first GENUS device is composed of a panel with light-emitting diode (LED) illumination and speakers for auditory stimulation, whilst the second device is composed of a small vibrating speaker for tactile stimulation. Each of the two groups will have different combinations of light, sound, and tactile settings.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gabrielle C de Weck, BS; Phone Number: 617-258-7723; Email: gdeweck@mit.edu
• Study Contact Backup: Name: Theresa Cho; Phone Number: 617-258-7723; Email: tdcmit23@mit.edu

Study Locations

• United States
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02139
      • Recruiting
      • Massachusetts Institute of Technology
      • Contact: Gabrielle C de Weck, BS; Phone Number: 617-258-7723; Email: gdeweck@mit.edu
      • Principal Investigator: Li-Huei Tsai, PhD
      • Principal Investigator: Diane Chan, MD, PhD
      • Contact: Theresa Cho; Phone Number: 617-258-7723; Email: tdcmit23@mit.edu
      • Sub-Investigator: Gabrielle de Weck, BS
      • Sub-Investigator: Theresa Cho
      • Sub-Investigator: Kenji Aoki, BA
      • Sub-Investigator: Ute Geigenmuller, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject has Idiopathic PD defined by the cardinal sign, bradykinesia, plus the presence of at least 1 of the following: resting tremor or rigidity and without any other known or suspected cause of Parkinsonism (according to Movement disorder society (MDS) clinical diagnostic criteria for Parkinson's disease confirmed by a fellowship trained movements disorder specialist
• Subject is Hoehn & Yahr stage 2 to 3
• Subject has a Montreal Cognitive Assessment (MOCA) score ≥26.
• Subject is > 45 and <90 years of age.
• proficient in speaking, reading, and understanding English
• capable of providing informed written consent
• Subject is on a stable dose (at least 1 month prior to baseline visit) of antiparkinsonian agents and willing to remain on this dose for the duration of the study. If on a cholinesterase inhibitor, a stable dose without changes for 1 month is required.
• Subject has undergone a brain CT or MRI prior to rule out underlying structural lesions

Exclusion criteria:

• Subject has atypical Parkinson's syndrome(s) due to drugs, metabolic neurogenetic disorders (e.g., Wilson's Disease), encephalitis, cerebrovascular disease, or degenerative disease (e.g., Progressive Supranuclear Palsy, Multiple System Atrophy, Corticobasal Degeneration, Lewy Body dementia)
• history of any psychiatric illness that would pose a safety risk
• diagnosis of dementia or other neurological conditions
• currently taking sedative medications that are clinically contraindicated
• has undergone recent change (<1 month) in medication
• recent drug or alcohol abuse or dependence
• laboratory results the would pose safety risk
• concurrently or has participated in other clinical trial investigation within 3 months
• pregnant
• no healthcare
• history of epilepsy, stroke, or seizure in past 24 months
• diagnosis of migraines
• have certain implantable medical devices
• contraindications for MRI
• life expectancy of less than 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Parkinson's Active Arm; Exposure to active sensory stimulation (40Hz) for 30-60 minutes.	Device: GENUS device (Active Settings); Participants in the active, experimental group will use the GENUS devices configured to active (40Hz) setting for 30-60 minutes; Other Names: Gamma Frequency Stimulation; Light and Sound stimulation; Tactile stimulation
Sham Comparator: Parkinson's Control Arm; Exposure to control stimulation (sham) for 30-60 minutes.	Device: GENUS device (Sham settings); Participants in the control group will use the GENUS devices configured to the sham settings for 30-60 minutes; Other Names: Gamma frequency stimulation; Light and Sound stimulation; Tactile Stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of gamma frequency stimulation	Feasibility of gamma frequency stimulation in subjects with mild PD will be assessed by analyzing the EEG data from each subject for a sign of change in gamma frequency waves and determining the percent of subjects who show this change.	Immediately after completing the stimulation
Incidence of Stimulation-Related Adverse Events	Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects.	Immediately after the completion of the stimulation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cognitive performance after gamma frequency stimulation	Exploratory measure to check if there is any change in cognitive performance, between baseline and immediately after the completion of stimulation. The CANTAB testing battery will be used to test for attention, memory, psychomotor speed, and executive function.	baseline and immediately after the completion of the stimulation

Collaborators and Investigators

• Sponsor: Massachusetts Institute of Technology
• Investigators: Principal Investigator: Li-Huei Tsai, PhD, Massachusetts Institute of Technology; Principal Investigator: Diane Chan, PhD, Massachusetts Institute of Technology

Publications and helpful links

General Publications

• Okun MS. Deep-brain stimulation for Parkinson's disease. N Engl J Med. 2012 Oct 18;367(16):1529-38. doi: 10.1056/NEJMct1208070. No abstract available.
• Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, Daniels C, Deutschlander A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W, Voges J; German Parkinson Study Group, Neurostimulation Section. A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006 Aug 31;355(9):896-908. doi: 10.1056/NEJMoa060281. Erratum In: N Engl J Med. 2006 Sep 21;355(12):1289.
• Brown P. Oscillatory nature of human basal ganglia activity: relationship to the pathophysiology of Parkinson's disease. Mov Disord. 2003 Apr;18(4):357-63. doi: 10.1002/mds.10358.
• Brown P, Oliviero A, Mazzone P, Insola A, Tonali P, Di Lazzaro V. Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson's disease. J Neurosci. 2001 Feb 1;21(3):1033-8. doi: 10.1523/JNEUROSCI.21-03-01033.2001.
• Heusinkveld LE, Hacker ML, Turchan M, Davis TL, Charles D. Impact of Tremor on Patients With Early Stage Parkinson's Disease. Front Neurol. 2018 Aug 3;9:628. doi: 10.3389/fneur.2018.00628. eCollection 2018.
• Kogan M, McGuire M, Riley J. Deep Brain Stimulation for Parkinson Disease. Neurosurg Clin N Am. 2019 Apr;30(2):137-146. doi: 10.1016/j.nec.2019.01.001.
• Litvak V, Eusebio A, Jha A, Oostenveld R, Barnes G, Foltynie T, Limousin P, Zrinzo L, Hariz MI, Friston K, Brown P. Movement-related changes in local and long-range synchronization in Parkinson's disease revealed by simultaneous magnetoencephalography and intracranial recordings. J Neurosci. 2012 Aug 1;32(31):10541-53. doi: 10.1523/JNEUROSCI.0767-12.2012.
• Muthuraman M, Bange M, Koirala N, Ciolac D, Pintea B, Glaser M, Tinkhauser G, Brown P, Deuschl G, Groppa S. Cross-frequency coupling between gamma oscillations and deep brain stimulation frequency in Parkinson's disease. Brain. 2020 Dec 5;143(11):3393-3407. doi: 10.1093/brain/awaa297.
• Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE 4th, Wang X, Gordon CW Jr, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD. Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial. Ann Neurol. 2009 May;65(5):586-95. doi: 10.1002/ana.21596.

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2022
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: January 6, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): March 7, 2022

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Gamma; Light and Sound Stimulation; Tactile Stimulation; Motor Impairment; Non-Invasive Sensory Stimulation
• 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: 2110000486

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