Novel DBS Stimulation Patterns for Treatment of Parkinson's Disease

Novel DBS Stimulation Patterns for Treatment of Parkinson's Disease - UNMC/Medtronic Collaborative Acute Feasibility Pilot

This is an open-label, non-randomized, proof-of-concept comparison of clinical vs. research stimulation patterns in patients with Parkinson's disease (PD) being treated with Deep Brain Stimulation (DBS) through the Medtronic Percept PC DBS device. The investigators hypothesize that stimulation patterns designed to better target excessive synchrony in a patient-tailored manner may result in more efficient and effective therapy with fewer side effects. Medtronic 3rd-generation sensing implantable neural stimulator, Percept PC, is FDA-approved for treating PD. The Percept PC device features BrainSense, the first and only available sensing technology for deep brain stimulation. BrainSense technology allows the device to capture and record brain signals (local field potentials, or LFP) using the brain-implanted DBS lead, while simultaneously delivering therapeutic stimulation. Investigators plan to enroll and complete investigations in 15 study subjects total, who have been previously implanted with the Medtronic Percept PC for the treatment of PD, and who are optimized for clinical stimulation and anti-Parkinsons medication. Investigations will be performed in UNMC Movement Disorders Clinic, UNMC Neurosurgery Lab, and UNO Biomechanics Research Building, Gait Lab. Subjects will receive research stimulation patterns and the effect on PD motor symptoms will be assessed via Unified Parkinsons Disease Rating Scale (UPDRS)-part III and gait measures. Videotaping of patient UPDRS-III testing and gait will be obtained.

Study Overview

• Status: Recruiting
• Conditions: Parkinson's Disease
• Intervention / Treatment: Device: Novel DBS stimulation patterns

Detailed Description

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms. Motor symptoms of PD include the clinical triad of tremor, rigidity, and bradykinesia, and typically lead to the initial diagnosis. While there is yet no cure for PD, medical and surgical therapies have been developed that effectively target the motor symptoms of PD. Patients with PD who demonstrate significant motor fluctuations and dyskinesia are considered for subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. Therapeutic DBS leads to a reduction in pathological neuronal synchronization seen in PD. While continuous high-frequency stimulation is effective for ameliorating motor symptoms, the investigators hypothesize that different stimulation patterns which are designed to better target excessive synchrony in a patient-tailored manner, may result in more efficient and effective therapy with fewer side effects. This overarching hypothesis is supported by prior foundational preclinical and clinical research. Medtronic has developed proprietary technology that allows implantable neural stimulators (INS) to deliver both standard clinical electrical stimulation therapy and to record bioelectric data (i.e. local field potentials; LFPs) through DBS leads implanted in the brain. Medtronic's 3rd-generation sensing DBS INS, Percept PC, is FDA-approved for treating PD and can be used to explore unique biomarkers of brain state changes associated with activities of daily living and disease symptomatic states.

This research will use Percept PC INS latent capabilities to deliver research stimulation. Importantly, all stimulation in this research project will be delivered using charge-balanced pulses, in compliance with all FDA safety guidelines including frequency (≤ 250 Hz) and charge density (30 µC/cm2/phase). At the conclusion of the research study, standard clinical stimulation will be re-activated.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dulce Maroni, PhD; Phone Number: 402-215-3053; Email: dmaroni@unmc.edu
• Study Contact Backup: Name: Jonathan Nguyen; Phone Number: 402-836-9407; Email: jon.nguyen@unmc.edu

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68118
      • Recruiting
      • Unversity of Nebraska Medical Center
      • Contact: Dulce Maroni, PhD; Phone Number: 402-215-3053; Email: dmaroni@unmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with idiopathic Parkinson's Disease who were recommended for STN DBS using standard clinical inclusion and exclusion criteria (e.g., presence of coagulopathy, dementia, untreated depression, pre-existing implanted stimulation system, prior intracranial surgery, history of alcohol or drug abuse)
• Patients have been previously implanted with bilateral STN DBS and the Medtronic Percept PC implantable neural stimulator.
• Patients are optimized for clinical stimulation and medication for at least 3 months post-surgery for the implantation of their DBS system.
• Consent to study participation
• Presence of a robust beta peak (detectable using the Percept BrainSense Survey feature; ≥ 0.7 µV/rtHz), intra-operatively (assessed via Lead Confirm technology from Alpha Omega)
• Good response to stimulation (30% improvement on UPDRS III compared to baseline OFF), at least 3 months post-surgery.

Exclusion Criteria:

• Not currently implanted with the Medtronic Percept INS
• Not willing to participate in the study
• Unstable stimulation with need for frequent reprogramming or further adjustment
• Significant stimulation-induced side effects
• Need for unusual programming parameters such as very high (> 200 Hz) or low (< 100) frequencies (due to cycle limitations)
• The patient has an implanted cardiac device
• The patients Medtronic Percept TM PC indicates elective-replacement-indicated (ERI) at the start of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD with DBS; Patients with Parkinson's Disease who were implanted with Medtronic Percept PC for DBS and consent to participate in the study.	Device: Novel DBS stimulation patterns; Stimulation patterns

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of novel DBS stimulation patterns.	To assess if the novel stimulation patterns provide similar side effect profile, when compared to standard clinical stimulation, tolerability will be assessed by: Number of study participants experiencing stimulation-related side effects. Side effects will be measured as patient-reported severity and type of side effect.; Number of study participants experiencing stimulation-related Adverse Events.	Years 1-2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to novel DBS stimulation patterns.	To assess if the novel stimulation patterns provide similar motor symptom benefit, when compared to standard clinical stimulation, response will be assessed by: UPDRS Part III exam instrumented with inertial sensors will provide severity scores from 0-4 for tremor, bradykinesia, rigidity and dyskinesia.; Balance and gait measures will be obtained by inertial sensors placed in the extremities.	Years 1-2

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Aviva Abosch, MD, PhD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Estimated): March 22, 2025
• Study Completion (Estimated): March 22, 2025

Study Registration Dates

• First Submitted: March 12, 2021
• First Submitted That Met QC Criteria: March 12, 2021
• First Posted (Actual): March 16, 2021

Study Record Updates

• Last Update Posted (Actual): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

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: 0865-20-FB

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