Evaluation of Neurocognitive Changes in Parkinson's Disease After Low Frequency Burst Stimulation

Theta Burst Subthalamic Nucleus Deep Brain Stimulation for Cognitive and Motor Improvements in Parkinson's Disease

This study aims to determine whether direct brain stimulation of specific regions and ranges improves cognition in people with Parkinsons Disease (PD) who already have a deep brain stimulator implanted. Research activities consist of 32 subjects undergoing stimulation changes to their device and being administered neurocognitive tests to evaluate the changes. An fMRI scan will also be done at baseline and at weeks 15 and 27.

All subjects will undergo the stimulation changes in a randomized double blind crossover study. Evaluation of stimulation changes will be assessed through analysis of neurocognitive data.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: STN DBS - Theta Burst; Device: STN DBS - Gamma

Detailed Description

In this single-center pilot study, the investigators will study both acute and chronic changes to neurocognitive and motor performance in response to interleaving gamma/theta (theta burst) stimulation compared to standard-of-care gamma stimulation.

This study will be a randomized double-blinded crossover study. Each patient's baseline voltage intensity will be unchanged. During the first outpatient visit, a baseline assessment (under baseline stimulation parameters, including frequency, pulse width and voltage) consisting of motor and cognitive tests will first be performed. After one week of titration on the theta burst stimulation paradigm, all patients will randomized to either baseline or theta burst stimulation settings for one week. Motor testing (UPDRS) and neuropsychological testing will be performed after this week. Each patient will then be programmed to the other stimulation paradigm for another week. At the end of this third week, neuropsychological and motor testing will again be performed.

Patients will again be randomized into either baseline gamma stimulation or theta burst stimulation for the chronic phase of the study. Repeat neuropsychological and motor testing will be performed at three months. Each patient will switched to the other stimulation strategy and repeat neuropsychological and motor testing will be performed after another three months. After the first 6 months, patients will be placed on open-label theta burst stimulation for 6 months (total of one year). At the end of one year, patients will undergo repeat neuropsychological and motor testing, after which they will be reprogrammed to their initial settings or given the option to remain on theta burst stimulation parameters. Functional magnetic resonance imaging will be acquired during baseline, week 15, and week 27 visits for patients with compatible devices that meet the inclusion criteria.

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

Contacts and Locations

• Study Contact: Name: Darrin Lee, MD PhD; Phone Number: 9495220866; Email: darrin.lee@med.usc.edu
• Study Contact Backup: Name: Wooseong Choi, BS; Phone Number: 8474017335; Email: wooseong@usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California Keck School of Medicine
      • Contact: Darrin Lee; Phone Number: 949-522-0866; Email: Darrin.Lee@med.usc.edu
      • Contact: Wooseong Choi; Phone Number: 8474017335; Email: wooseong@usc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients who had previously undergone bilateral STN deep brain stimulation implantation
2. Age >18 years old
3. Stable medication regimen for at least 3 months.
4. Patient informed and able to give written consent
5. Able to comply with all testing, follow-ups and study appointments and protocols

Exclusion Criteria:

1. History of epilepsy or seizure
2. History of dementia
3. History of major substance abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; double-blinded randomization into theta burst stimulation followed by baseline stimulation	Device: STN DBS - Theta Burst; 200 Hz intraburst stimulation for 0.1 second repeated at intervals of 5hz with an existing device; Device: STN DBS - Gamma; Standard of care gamma stimulation with an existing device
Experimental: Group B; double blinded randomization into baseline stimulation followed by theta burst stimulation	Device: STN DBS - Theta Burst; 200 Hz intraburst stimulation for 0.1 second repeated at intervals of 5hz with an existing device; Device: STN DBS - Gamma; Standard of care gamma stimulation with an existing device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of motor symptoms	Effects of theta burst stimulation on changes in baseline motor symptoms will be assessed using the MDS-Unified Parkinson's Disease Rating Scale - Sections III&IV (MDS-UPDRS III&IV)	Baseline, Week 1, Week 2, Week 3, Week 15, Week 27
Evaluation of executive functioning	Effects of theta burst stimulation on changes in baseline cognitive symptoms will be assessed using Delis-Kaplan Executive Function System (D-KEFS).	Baseline, Week 1, Week 2, Week 3, Week 15, Week 27
Neuroimaging	Effects of theta burst stimulation on changes in baseline resting state functional connectivity will be assessed using functional magnetic resonance imaging.	Baseline, Week 15, Week 27

Collaborators and Investigators

• Sponsor: University of Southern California
• Investigators: Principal Investigator: Darrin Lee, MD PhD, University of Southern California, Keck School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2022
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Deep Brain Stimulation
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: HS-20-00676

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