Movement State-dependent Adaptive DBS for PD

Official title

Movement State-Dependent Adaptive Deep Brain Stimulation for Parkinson's Disease

Overview

This is a single-center clinical study aiming to improve gait functions in patients with Parkinson's Disease (PD) by using adaptive neurostimulation to the pallidum. The investigators will use a bidirectional deep brain stimulation device with sensing and stimulation capabilities to 1) identify neural biomarkers to detect the onset of walking by recording neural activities from the motor cortical areas and the globus pallidus, 2) understand the impacts of changes in DBS parameters on gait kinematics and optimize setting parameters for enhancing walking performance, 3) develop a movement state-dependent adaptive deep brain stimulation (DBS) paradigm to automatically switch stimulation settings according to different movement states (i.e., walking vs non-walking). The proposed therapy will deliver personalized neurostimulation based on individual physiological biomarkers to enhance gait function in patients with PD. 6 patients with idiopathic Parkinson's disease who have already been implanted with the Medtronic Summit RC+S device will be enrolled in this study.

Detailed description

This study will allow the investigators to evaluate the efficacy of a movement state-dependent adaptive deep brain stimulation paradigm to treat gait dysfunction in individuals with Parkinson's disease (PD).

While current DBS therapy improves the appendicular symptoms of PD, such as tremor and bradykinesia, it is less effective for advanced gait symptoms, which manifest as hypokinetic gait patterns, increased gait variability, asymmetry, and disturbed balance. These symptoms are debilitating and represent a major source of morbidity for patients with PD. Studies have suggested that while conventional high-frequency stimulation settings are good at treating appendicular symptoms, they may not be as effective for axial symptoms such as gait disorders. Modulating stimulation parameters, by using lower frequencies, for instance, has been shown to improve gait kinematics such as symmetry and rhythmicity. However, these settings are less effective for other symptoms and therefore come at the expense of appendicular symptom control. The overall objective of this study is to identify personalized electrophysiological signatures of movement state and gait-optimized stimulation parameters in PD patients to enable adaptive control algorithms that automatically switch from identified 'gait-optimized' settings during walking to 'other PD symptom-optimized' settings during non-walking.

This is a small, double-blinded trial, six patients with idiopathic PD and motor fluctuations who have already been implanted with the RC+S devices. The investigators will compare the overall efficacy of closed-loop (adaptive DBS) and open-loop (continuous clinical DBS) paradigms in terms of behavioral performance improvements. During this chronic movement state-dependent adaptive DBS phase, adaptive DBS and open-loop stimulation settings will be randomized for 7-day periods, and motor and gait-related measurements will be obtained from wearable devices that track movement kinematics. Patients will participate in daily, if possible, motor and gait tasks at home and are asked to fill out motor diary questionnaires to share their feedback from both motor and non-motor perspectives.

The investigators expect to successfully develop a prototype movement state-dependent adaptive DBS algorithm. They hypothesize that the embedded closed-loop, movement state-dependent adaptive DBS paradigm will improve gait function compared to the conventional open-loop approach, in which stimulation parameters remain constant, while maintaining the standard therapeutic benefits of DBS.

Interventions

• Device Summit RC+S
  Participants receive gait-optimized stimulation settings while walking and Parkinson's disease symptom-optimized settings during non-walking periods.
• Device Summit RC+S
  Participants receive clinically-optimized open-loop deep brain stimulation ot the pallidum.

Primary outcome measures

• Change in Mini Balance Evaluation Systems Test (Mini-BESTest) Scores [Time frame: after each 7 day block]
• Change in Gait [Time frame: 14 day long-term testing period]
• Change in Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III scores [Time frame: after each 7 day block]
• Change in Stride Length [Time frame: 14 day long-term testing period]
• Change in Stride Time [Time frame: 14 day long-term testing period]
• Change in Double Support Time [Time frame: 14 day long-term testing period]
• Change in number of freezes [Time frame: 14 day long-term testing period]
• Change in number of falls [Time frame: 14 day long-term testing period]
• Change in Activities-Specific Balance Confidence (ABC) Scale [Time frame: once per day during 14 day long-term testing period]

Secondary outcome measures (2)

• Change in Montreal Cognitive Assessment (MoCA) scores [Time frame: after each 7 day block]
• Changes in Parkinson's Disease (PD) Symptoms Questionnaire [Time frame: once per day during 14 day long-term testing period]

Eligibility criteria

Inclusion criteria

• Ability to give informed consent for the study
• Subjects implanted with Summit RC+S investigational DBS system.
• Absence of significant cognitive impairment (score of 21 or greater on the Montreal Cognitive Assessment (MoCA)
• Signed informed consent
• Age 21-75
• Diagnosis of idiopathic PD with duration of motor symptoms for 3 years or greater
• Patient has undergone appropriate therapy with oral medications with inadequate relief as determined by a movement disorders neurologist.
• UPDRS-III score off medication between 20 and 80 and an improvement of at least 30% in the baseline UPDRS-III on medication score, compared to the baseline off-medication score, and motor fluctuations with at least 2 hours per day of on time without dyskinesia or with non-bothersome dyskinesia. OR Patients with tremor-dominant PD (a tremor score of at least 2 on a UPDRS-III sub-score for tremor), treatment resistant, with significant functional disability despite maximal medical management
• Patients with gait impairments: slowed gait, shuffling steps, postural instability, or freezing of gait off medication.

Exclusion criteria

• Inability to comply with study procedures
• Patients who cannot walk (wheelchair bound)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 1 center

• UCSF — San Francisco

Publications

• Little S, Pogosyan A, Neal S, Zavala B, Zrinzo L, Hariz M, Foltynie T, Limousin P, Ashkan K, FitzGerald J, Green AL, Aziz TZ, Brown P. Adaptive deep brain stimulation in advanced Parkinson disease. Ann Neurol. 2013 Sep;74(3):449-57. doi: 10.1002/ana.23951. Epub 2013 Jul 12. PMID 23852650
• Wang D, Ramesh R, Azgomi HF, Louie K, Balakid J, Marks J. At-Home Movement State Classification Using Totally Implantable Bidirectional Cortical-Basal Ganglia Neural Interface. Res Sq [Preprint]. 2025 Mar 12:rs.3.rs-6058394. doi: 10.21203/rs.3.rs-6058394/v1. PMID 40162212
• Azgomi HF, Louie KH, Bath JE, Presbrey KN, Balakid JP, Marks JH, Wozny TA, Galifianakis NB, Luciano MS, Little S, Starr PA, Wang DD. Modeling and Optimizing Deep Brain Stimulation to Enhance Gait in Parkinson's Disease: Personalized Treatment with Neurophysiological Insights. medRxiv [Preprint]. 2024 Nov 1:2024.10.30.24316305. doi: 10.1101/2024.10.30.24316305. PMID 39574845

Identifiers

NCT: NCT07424508 · 25-45335

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗