Adaptive Deep Brain Stimulation to Improve Motor and Gait Functions in Parkinson's Disease

NCT04675398 | Active Not Recruiting DMC FDA Device

• 1 other identifier: 18649
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center phase I 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) decode the physiological signatures of gait and gait adaptation by recording neural activities from the motor cortical areas and the globus pallidus during natural walking and a gait adaptation task, and 2) develop an adaptive deep brain stimulation (DBS) paradigm to selectively stimulate the pallidum during different phases of the gait cycle and measure improvements in gait parameters. This is the first exploration of network dynamics of gait in PD using chronically implanted cortical and subcortical electrodes. In addition to providing insights into a fundamental process, the proposed therapy will deliver personalized neurostimulation based on individual physiological biomarkers to enhance locomotor skills in patients with PD. Ten patients with idiopathic Parkinson's disease undergoing evaluation for DBS implantation will be enrolled in this single treatment arm study.

Conditions

Parkinson Disease

Keywords

neuromodulation; closed-loop deep brain stimulation; gait impairments; motor learning; parkinson's disease

Outcome Measures

Primary Outcomes (3)

• Change in motor learning task completion with closed-loop compared to open-loop deep brain stimulation (DBS)

  Change in percentage of motor learning task trials that were completed with closed-loop compared to open-loop deep brain stimulation (DBS). The task is made up of 840 trials, completion will be measured by percent of trials completed (e.g. 750/840 trials completed would be 89%). The task has a built in function which logs completed trials in a CSV document.

  Baseline and 2 years

• Change in motor learning task reaction times with closed-loop compared to open-loop deep brain stimulation (DBS)

  Change in gait sequence motor learning task reaction times (measured in milliseconds) with closed-loop compared to open-loop deep brain stimulation (DBS).

  Baseline and 2 years

• Change in motor learning task mean accuracy with closed-loop compared to open-loop deep brain stimulation (DBS).

  Change in motor learning task mean accuracy with closed-loop compared to open-loop deep brain stimulation (DBS). Accuracy will be measured as a percent using the tasks proprietary output log which records which trials out of the 840 total trials were target hits (i.e. correct trials). Mean accuracy will be calculated by taking the average of each patient's accuracy score across all attempts of the task done by said patient.

  Baseline and 2 years

Secondary Outcomes (8)

• Change in Gait

  Baseline and 2 years

• Change in Balance

  Baseline and 2 years

• Change in MDS-UPDRS III scores

  Baseline and 2 years

• Change in NIHTB Cognition Battery Test

  Baseline and 2 years

• Change in Five-Times Sit to Stand Test Results

  Baseline and 2 years

Study Arms (4)

Open-loop deep brain stimulation

ACTIVE COMPARATOR

Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving open-loop deep brain stimulation.

Device: Summit RC+S

Randomized deep brain stimulation

ACTIVE COMPARATOR

Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving closed-loop stimulation at random time points.

Device: Summit RC+S

Deep brain stimulation during contralateral limb movement

ACTIVE COMPARATOR

Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving closed-loop stimulation during time of contralateral limb movement.

Device: Summit RC+S

Deep brain stimulation during contralateral limb rest

ACTIVE COMPARATOR

Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving closed-loop stimulation during time of no movement for contralateral limb.

Device: Summit RC+S

Interventions

Summit RC+S DEVICE

Using the RC+S pulse generator, patients receive clinically-optimized open loop DBS stimulation to the pallidum.

Also known as: continuous deep brain stimulation

Open-loop deep brain stimulation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to give informed consent for the study
• Movement disorder symptoms that are sufficiently severe, in spite of best medical therapy, to warrant surgical implantation of deep brain stimulators according to standard clinical criteria
• Patient has requested surgical intervention with deep brain stimulation for their disorder
• No movement -elated abnormalities that suggest an alternative diagnosis or contraindicate surgery
• Absence of significant cognitive impairment (score of 21 or greater on the Montreal Cognitive Assessment (MoCA),
• Signed informed consent
• Ability to comply with study follow-up visits for brain recording, testing of adaptive stimulation, and clinical assessment.
• 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.
• Ability of patient and/or caregivers to recharge the system evaluated by all clinicians and study personnel.
• Geographical proximity and/or ability to travel to study sites for patient to receive re-programming via investigational devices (e.g. Summit Research Laboratory Programmer).

You may not qualify if:

• Coagulopathy, anticoagulant medications, uncontrolled hypertension, history of seizures, heart disease, or other medical conditions considered to place the patient at elevated risk for surgical complications
• Evidence of a psychogenic movement disorder: Motor symptoms that remit with suggestion or "while unobserved", symptoms that are inconsistent over time or incongruent with clinical condition, plus other manifestation such as "false" signs, multiple somatizations, or obvious psychiatric disturbance.
• Pregnancy: all women of child bearing potential will have a negative urine pregnancy test prior to undergoing their surgical procedure.
• Significant untreated depression (BDI-II score \>20). History of suicidal attempt or active suicidal ideation (Yes to #2-5 on C-SSRS)
• Any personality or mood symptoms that study personnel believe will interfere with study requirements.
• Subjects who require electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS) or diathermy
• Implanted stimulation systems such as; cochlear implant, pacemaker, defibrillator, or neurostimulator
• Previous cranial surgery
• Drug or alcohol abuse
• Meets criteria for Parkinson's disease with mild cognitive impairment (PD-MCI). These criteria are: performance of more than two standard deviations below appropriate norms, for tests from two or more of these five cognitive domains: attention, executive function, language, memory, and visuospatial tests.
• Known allergies to the implantable device components including titanium, polyurethane, silicone, and nylon.

Sponsors & Collaborators

• Michael J. Fox Foundation for Parkinson's Research: collaborator
• Doris Wang, MD, PhD: lead
• Burroughs Wellcome: collaborator

Study Sites (1)

UCSF

San Francisco, California, 94134, United States

Location

Related Publications (2)

• Swann NC, de Hemptinne C, Miocinovic S, Qasim S, Ostrem JL, Galifianakis NB, Luciano MS, Wang SS, Ziman N, Taylor R, Starr PA. Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease. J Neurosurg. 2018 Feb;128(2):605-616. doi: 10.3171/2016.11.JNS161162. Epub 2017 Apr 14.

  PMID: 28409730 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Doris Wang, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: In a small, double-blinded trial, the investigators will compare the overall efficacy of closed-loop and open-loop paradigms in terms of behavioral performance improvements in validated motor skill learning tasks and measurements from wearable devices. During this chronic aDBS phase, aDBS and open-loop stimulation settings will be randomized for 30-day periods and motor skill and gait related measurements will be obtained from a combination of computerized motor tasks and wearable devices that track movement kinematics. Patients will participate in daily, if possible, motor learning and gait tasks at home with triggered stimulation settings and recordings. Data will be collected and reviewed from the wearable monitors, Summit RC+S, and home motor learning tasks remotely. Researchers will have weekly check-in sessions with patients by video conferencing or in-person meetings. At minimum, researchers will have in-person sessions with patients every 4 weeks during Phase 3.

Study Record Dates

• First Submitted: September 23, 2020
• First Posted: December 19, 2020
• Study Start: June 15, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): April 1, 2030
• Last Updated: May 1, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)