Stimulus-Evoked Directional Field Potentials to Guide Subthalamic and Pallidal DBS for PD

NCT06169852 | Recruiting DMC FDA Device

• 2 other identifiers: IRB-300011568UH3NS130202
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Our goal is to better understand how DBS modifies local neuronal activity and to pioneer device technologies that can record local DBS-evoked potentials (DLEPs) to guide therapy. Our vision is for a patient's unique electrophysiology to guide both electrode targeting during surgery and programming in clinic, eventually as an integrated component of the implanted pulse generator. Our results will inform directional DBS for PD and serve as a model for translation to other diseases where knowledge on DBS circuit interactions is at an even earlier stage.

Conditions

Parkinson Disease

Keywords

Parkinson's Disease; Deep Brain Stimulation; DBS

Outcome Measures

Primary Outcomes (3)

• Validate the biological origin of brain signals using an external stimulation/recording system during standard of care Deep Brain Stimulation surgery, both awake and under general anesthesia.

  The investigator will validate the biological origin of the signals using pairs of DBS pulses and neural refractoriness with an external stimulation/recording system at therapeutically relevant stimulus amplitudes (i.e., inside and outside the therapeutic window).

  At standard of care DBS surgery (awake) and approximately one week later at standard of care battery placement (under general anesthesia).

• Test whether directional DBS leads elicit spatiotemporally distinct oscillations in subthalamic nucleus versus globus pallidus interna.

  This investigators efforts will yield granular spatial maps of neural engagement across the two canonical targets for PD to guide targeting (awake or under anesthesia) and clinical programming.

  At standard of care DBS surgery (awake) and approximately one week later at standard of care battery placement (under general anesthesia).

• Test whether spatial maps of DBS-evoked oscillations predict clinically effective stimulation sites on a directional DBS lead.

  The investigator will test whether spatial maps of DBS-evoked neural activity predict clinically effective locations for directional DBS.

  At standard of care DBS surgery (awake), approximately one week later at standard of care battery placement (under general anesthesia), at in a research clinical assessment at 16 months after DBS surgery.

Study Arms (3)

Arm 1 (0-4 months)

EXPERIMENTAL

In this arm we will stimulate from either STN alone, GPi alone, or a combination of both STN and GPi.

Device: Unilateral dual-target (STN/GPi) DBS

Arm 2 (4-8 months)

EXPERIMENTAL

In this arm we will stimulate from either STN alone, GPi alone, or a combination of both STN and GPi, whichever was not used in Arm 1.

Device: Unilateral dual-target (STN/GPi) DBS

Arm 3 (8-12 months)

EXPERIMENTAL

In this arm we will stimulate from either STN alone, GPi alone, or a combination of both STN and GPi, whichever was not used in Arms 1 and 2.

Device: Unilateral dual-target (STN/GPi) DBS

Interventions

Unilateral dual-target (STN/GPi) DBS DEVICE

Participants will be randomly assigned either DBS stimulation in the STN alone, GPi alone, or a combination of stimulation in the STN and GPi.

Arm 1 (0-4 months); Arm 2 (4-8 months); Arm 3 (8-12 months)

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years and older.
• Clinically definite, advanced idiopathic PD based on at least 2 of 3 cardinal PD features (tremor, rigidity, and/or bradykinesia).
• Disease duration of 4 years or more.
• Participant has elected to undergo awake DBS surgery as part of routine care, and the subthalamic nucleus (STN) or globus pallidus interna (GPi) are recommended by the multidisciplinary DBS committee as the surgical target.
• For participants who opt for the dual-target strategy, neurosurgery judges that dual-target STN and GPi implant is an appropriate option with acceptable safety profile.
• Participant is healthy enough to undergo surgery and the research protocol.
• Normal, or essentially normal, preoperative brain MRI, except for expected mild abnormalities associated with advanced PD.
• Willingness and ability to cooperate during awake DBS surgery, as well as during post-operative evaluations, adjustments of medications and stimulator settings.
• Participant's health insurance and/or Medicare covers DBS surgery as part of routine care.
• Refractory motor symptoms such as dyskinesias, wearing off, and/or motor fluctuations, causing significant disability or occupational dysfunction, despite reasonable attempts at medical management, as determined by our consensus DBS committee.
• Stable doses of PD medications for at least 28 days prior to baseline assessments.
• Improvement of motor signs ≥30% with dopaminergic medication as assessed with the use of the Movement Disorders - Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III; scores range from 0 to 108, with higher scores indicating worse functioning). One exception to this 30% threshold is patients who have typical features of PD but cannot take levodopa because of unacceptable side effects.19
• Disease severity ratings above Hoehn and Yahr stage 2.5, defined as unilateral involvement only with minimal or no functional disability, with scores ranging from 0 to 5 and higher scores indicating more severe disease.
• Score of more than 6 for activities of daily living in the worst "off" medication condition despite medical treatment, as assessed with the use of the MDS-UPDRS II (scores range from 0 to 52, with higher scores indicating worse functioning), or mild-to-moderate impairment in social and occupational functioning (score of 51 to 80% on the Social and Occupational Functioning Assessment Scale with scores ranging from 1 to 100 and lower scores indicating worse functioning).
• Dementia Rating Scale-2 (DRS-2) score of ≥130 on medications.

You may not qualify if:

• Age \<18 years.
• Participant's insurance will not cover the costs of surgery with an investigational device (Aims 2 and 3 only).
• Medical contraindications such as current uncontrolled hypertension, heart disease, coagulopathy, or other conditions contraindicating DBS surgery or stimulation.
• Duration of disease of \<4 years
• Clinical team suspects patient will need staged contralateral DBS for clinical symptoms within 1 year of unilateral DBS surgery.
• Diagnosis or suspicion of atypical parkinsonism (progressive supranuclear palsy, multiple system atrophy, corticobasal syndrome) or drug-induced parkinsonism, or significant neurological disease other than Parkinson's disease.
• Diagnosis of psychogenic movement disorder based on consensus criteria.
• Dual-target implant cannot be performed safely from a single burr hole because of anatomic constraints or cortical vascular anatomy, based upon the pre-operative neurosurgery plan.
• Patient is undergoing DBS electrode placement under general anesthesia without awake electrophysiological and clinical testing during implant.
• Score of \>25 on the Beck Depression Inventory II, with scores ranging from 0 to 63 and higher scores indicating worse functioning), or history of suicide attempt.
• An indication of suicidal ideation or active suicide planning as assessed on the Columbia-Suicide Severity Rating Scale.
• Any current acute psychosis, alcohol abuse or drug abuse.
• Clinical dementia (score of ≤130 on the Mattis Dementia Rating Scale with scores ranging from 0 to 144 and higher scores indicating better functioning).
• Ongoing or pervasive impulse control disorder not resolved by reduction of dopaminergic medications.
• Use of anticoagulant medications that cannot be discontinued during perioperative period.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Interventions

Deep Brain 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; Surgical Procedures, Operative

Study Officials

• Harrison Walker, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Harrison Walker, MD

CONTACT

205-934-0683; hcwalker@uabmc.edu

Christopher Gonzalez

CONTACT

205-975-3732; clgonzalez@uabmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomly assigned each of three different stimulation paradigms for 4 month intervals. Participants and researchers will be blinded to the stimulation paradigm used at any given point in the study.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: We are investigating unilateral dual-target DBS. The stimulation paradigms utilized include STN DBS alone, GPi DBS alone, and combined STN/GPi DBS.

Study Record Dates

• First Submitted: November 15, 2023
• First Posted: December 14, 2023
• Study Start: January 12, 2024
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Access Criteria: All data resulting from this project are available upon messaging, email, or written request through the Data Archive for the BRAIN Initiative (PI Dr. Toga at University of Southern California).

Locations

US (1)