Bilateral Closed Loop Deep Brain Stimulation for Freezing of Gait Using Neural and Kinematic Feedback

Deep Brain Stimulation of the subthalamic nucleus (STN) has become a standard of care, FDA-approved treatment for Parkinson's disease, with stimulation delivered at a constant amplitude and voltage, operating in an open-loop fashion that does not respond to a patient's current state. Although gait deficits and freezing of gait may initially respond to continuous open-loop deep brain stimulation (olDBS) and medication, the symptoms often recur over time.

The episodic and predictable nature of FOG makes it well suited for adaptive DBS (aDBS) and a device that overcomes the limitations of traditional high frequency olDBS and is capable of adapting therapy either in the frequency or intensity domain transiently to treat FOG while also treating other PD signs such as tremor and bradykinesia.

The purpose of this study is to determine the feasibility of an adaptive DBS system, that responds to patient-specific neural and kinematic variables with customized DBS parameters.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: Open Loop DBS; Device: Adaptive (Closed Loop) DBS; Device: Intermittent Open Loop DBS

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Helen Bronte-Stewart, MD MSE; Phone Number: 6507232116; Email: bronte-stewart-lab@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University
      • Contact: Sudeep Aditham; Phone Number: 650-723-6709; Email: bronte-stewart-lab@stanford.edu
      • Principal Investigator: Helen M Bronte-Stewart, MD MSE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinically-established PD
• Meets criteria for STN DBS eligibility as part of patient's standard medical care or already implanted in the STN with Percept(TM) PC
• The presence of complications of medication such as wearing off signs, fluctuating responses and/or dyskinesias, and/or medication refractory tremor, and/or impairment in the quality of life on or off medication due to these factors.
• Ability and willingness to return for study visits, at the initial programming and after three, six and twelve months of DBS.
• Age > 18
• Freezing of gait questionnaire (FOG-Q) score ≥ 1 and/or gait sub-score (Item 3.10) of MDS- UPDRS III ≥ 1
• Greater than or equal to 1.2 microVp between 8-35 Hz on either the LSTN or RSTN (Percept (TM) PC cohort only)

Exclusion Criteria:

• Dementia
• Untreated psychiatric disease
• Hoehn and Yahr stage 5 on or off medication (non-ambulatory)
• Age > 80
• Major surgical morbidities such as severe hypertension, coagulopathy and certain metabolic conditions that might increase the risk of hemorrhage or other surgical complications
• Presence of a cardiac pacemaker/defibrillator
• Inability to understand/sign consent
• Requires rTMS, ECT, MRI (Summit(R) RC+S cohort only), or diathermy
• Are pregnant or lactating
• Has a cranial metallic implant
• History of seizures or epilepsy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Device: Summit RC+S; Open Loop DBS: Standard DBS therapy at a constant frequency and voltage; Adaptive (Closed Loop) DBS: DBS that responds to neural or kinematic features of patient's current state; Intermittent Open Loop DBS: Control for aDBS - DBS intensity or frequency changes in a manner that mimics aDBS but is pre-determined and open loop rather than being responsive to neural or kinematic signals.	Device: Open Loop DBS; Standard DBS therapy at a constant frequency and voltage; Device: Adaptive (Closed Loop) DBS; DBS that responds to neural (Percept PC and Summit RC+S) or kinematic (Summit RC+S) features of patient's current state; Device: Intermittent Open Loop DBS; Control for aDBS - DBS intensity or frequency changes in a manner that mimics aDBS but is pre-determined and open loop rather than being responsive to neural or kinematic signals.
Experimental: Device: Percept PC; Open Loop DBS: Standard DBS therapy at a constant frequency and voltage; Adaptive (Closed Loop) DBS: DBS that responds to neural features of patient's current state	Device: Open Loop DBS; Standard DBS therapy at a constant frequency and voltage; Device: Adaptive (Closed Loop) DBS; DBS that responds to neural (Percept PC and Summit RC+S) or kinematic (Summit RC+S) features of patient's current state

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] related to Stimulation Condition	A Customized Adverse Events and Tolerability Questionnaire will measure the absence/presence and frequency of paresthesias, and muscle twitching relative to each stimulation condition	3 Months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] related to quality of life	The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, and IV will: (I) Evaluate mentation, behavior, and mood (II) Evaluate a patient's activities of daily life (IV) Measure the presence/severity of dyskinesias and other complications of therapy over time	3 Months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] related to speech	The Speech Intelligibility Test (SIT) will measure changes in speech related to each stimulation condition.	6 Months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] related to gait	The Freezing of Gait Questionnaire (FOG-Q) will be used to record changes in gait over time	3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait Parameters: Arrhythmicity	Variability in stride time during a gait task	Collected up to 10 days every 3 months
Gait Parameters: Mean Shank Angular Velocity	Average of the peak shank angular velocities of every stride during the gait task	Collected up to 10 days every 3 months
Gait Parameters: Mean Gait Cycle Time	Average length of time of each stride during a gait task	Collected up to 10 days every 3 months
Percent Time Freezing	The percentage of the gait task was a participant frozen	Collected up to 10 days every 3 months
The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III	Portion of the scale assesses the motor signs of PD. Each item is scored on a scale from 0 (normal) to 4 (severe), with the total possible score ranging from 0 to 132.	Collected up to 10 days every 3 months

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Helen M. Bronte-Stewart, MD,MSE, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2019
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (Actual): August 2, 2019

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

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: 52548

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes