Biomarkers to Guide Directional DBS for Parkinson's Disease

NCT03353688 | Completed Results FDA Device

• 2 other identifiers: IRB-1610180011UH3NS100553-01
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the clinical efficacy of directional DBS electrode technology and whether electrophysiology biomarkers can predict effective contact segments for chronic therapy.

Conditions

Parkinson Disease

Keywords

Parkinson's; Parkinson Disease

Outcome Measures

Primary Outcomes (2)

• Change From Preoperative Baseline in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS Part III) "Off" Medications

  A blinded examiner will measure Movement Disorders Society Unified Parkinson's Disease Rating Scale Part 3 motor scores "off" medications. MDS-UPDRS Part III is a motor examination consisting of 18 summed items where the investigator rates the severity of Parkinson's motor symptoms based on a scale of 0 - 4. Higher values indicate worse function (possible min score = 0, possible max score = 72). A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.

  2, 4, and 6 months post op

• Treatment Preference Survey Programming Strategy Preference

  Based on overall quality of life, participants will select their preference between directional and omnidirectional DBS.

  4 months post surgery

Secondary Outcomes (37)

• Change From Preoperative Baseline in the Beck Depression Inventory-2 (BDI-2)

  2, 4, and 6 months post op

• Change From Preoperative Baseline in the Beck Anxiety Inventory (BAI)

  2, 4, and 6 months post op

• Change From Preoperative Baseline in the Auditory Verbal Learning Test (AVLT) Delayed Recall Raw Score (Versions AB, CD, CR, GE)

  2, 4, and 6 months post op

• Change From Preoperative Baseline in the Auditory Verbal Learning Test (AVLT) Recognition Raw Score (Versions AB, CD, CR, GE)

  2, 4, and 6 months post op

• Change From Preoperative Baseline in the Auditory Verbal Learning Test (AVLT) Learning Raw Score (Versions AB, CD, CR, GE)

  2, 4, and 6 months post op

Study Arms (3)

Directional DBS guided by behavior

ACTIVE COMPARATOR

Directional stimulation with the Boston Scientific Vercise PC IPG with directional DBS lead, guided by behavioral assessments during device activation.

Device: Boston Scientific Vercise PC IPG with directional DBS lead

Omnidirectional DBS guided by behavior

PLACEBO COMPARATOR

Omnidirectional ("ring mode") stimulation with the Boston Scientific Vercise PC IPG with directional DBS lead, guided by behavioral assessments during device activation.

Device: Boston Scientific Vercise PC IPG with directional DBS lead

Directional DBS guided by biomarkers

ACTIVE COMPARATOR

Directional unilateral subthalamic stimulation with the Boston Scientific Vercise PC IPG with directional DBS lead, guided by electrophysiology biomarkers measured during surgery (nested exploratory treatment arm).

Device: Boston Scientific Vercise PC IPG with directional DBS lead

Interventions

Boston Scientific Vercise PC IPG with directional DBS lead DEVICE

Deep brain stimulation

Directional DBS guided by behavior; Directional DBS guided by biomarkers; Omnidirectional DBS guided by behavior

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years and ≤70 years.
• Clinically definite, advanced idiopathic PD based on at least 2 of 3 cardinal PD features (tremor, rigidity, or bradykinesia).
• Disease duration of 4 years or more.
• Participant has elected to undergo DBS surgery as part of routine care, and the subthalamic nucleus (STN) is recommended as the surgical target.
• Participant agrees to not undergo contralateral DBS for the other side of the brain until ≥ 12 months after initial DBS surgery.
• Participant is healthy enough to undergo surgery and the research protocol.
• Normal, or essentially normal, preoperative brain MRI.
• 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 tremor, 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).
• Disease severity ratings above Hoehn and Yahr stage 1, 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 or \>70 years.
• Participant's insurance will not cover the costs of surgery with the investigational device.
• Medical contraindications such as current uncontrolled hypertension, heart disease, coagulopathy, or other conditions contraindicating DBS surgery or stimulation.
• Duration of disease of \<4 years
• Participant or care team determine that contralateral DBS for the other side of the brain will likely be clinically indicated \<12 months after initial 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.
• Disease severity ratings of Hoehn and Yahr stage 1, 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.
• Diagnosis of psychogenic movement disorder based on consensus criteria.
• 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.
• 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.
• History of hemorrhagic stroke.
• Current or future risk of immunocompromise that might significantly increase risk of infection.

Sponsors & Collaborators

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

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (1)

• Black SD, Del Bene VA, Celka AS, Guthrie B, Martin RC, Olson J, Shumake J, Walker HC. Nascent visual artistic expression following right hemisphere subthalamic nucleus deep brain stimulation for Parkinson's disease. Parkinsonism Relat Disord. 2022 Jun;99:47-50. doi: 10.1016/j.parkreldis.2022.04.020. Epub 2022 May 1. No abstract available.

  PMID: 35598419 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Program Manger
• Organization: University of Alabama at Birmingham

clg17@uab.edu

(205) 934-0683

Study Officials

• Harrison Walker, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a triple blind study. Participants, raters, and investigator are masked to the assignment of directional versus omnidirectional unilateral subthalamic deep brain stimulation guided by behavioral programming for Parkinson's disease with motor fluctuations. For the nested exploratory arm evaluating directional DBS guided by electrophysiology biomarkers, the study is double-blind (investigator is not blinded).
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: This is a triple blind, randomized crossover study of directional versus omnidirectional unilateral subthalamic deep brain stimulation for Parkinson's disease with motor fluctuations.

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: November 27, 2017
• Study Start: November 3, 2017
• Primary Completion: August 15, 2022
• Study Completion: July 31, 2024
• Last Updated: September 19, 2024
• Results First Posted: April 15, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR, ANALYTIC CODE
• Time Frame: The data will be made available after analyses of the primary and secondary outcomes.
• Access Criteria: Users must set up an account on the DABI website to be able to access data.

Locations

US (1)