Deep Brain Stimulation (DBS) of the Pedunculopontine Nucleus (PPN)

NCT04605263 | Enrolling By Invitation DMC FDA Device

• 1 other identifier: PHX-19-500-412-30-04
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a mechanistic study to determine the differential effects of the dopaminergic and cholinergic systems on attention, gait, and balance. The primary goal of the study is to evaluate the relative effects of pedunculopontine nucleus (PPN) and subthalamic nucleus (STN) Deep Brain Stimulation (DBS) on these features in persons with Parkinson's Disease (PD) who are eligible for DBS for improvement of their motor symptoms and exhibit gait instability with falls. Patients will be enrolled and implanted with bilateral electrodes in one of the approved DBS locations (subthalamic nucleus: STN), but additionally electrodes will be inserted into the experimental target, namely the PPN bilaterally.

Conditions

Parkinson Disease

Keywords

Deep Brain Simulation (DBS); Gait and Balance; Postural Instability and Gait Dysfunction (PIGD)

Outcome Measures

Primary Outcomes (1)

• STN-PPN Stimulation Effect on Fall Risk

  The purpose of this study is to measure the effect and the mechanism of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) on fall risk as established by quantitative gait and balance analysis.

  27 months

Secondary Outcomes (7)

• STN-PPN on Linear and Nonlinear Measures of Gait

  27 months

• STN-PPN on Linear and Nonlinear Measures of Balance

  27 months

• STN-PPN on Attention

  27 months

• STN-PPN on Subjective Measures of Alertness

  27 months

• STN-PPN on Subjective Measures of Sleep

  27 months

Study Arms (2)

STN DBS

ACTIVE COMPARATOR

Subjects will receive traditional bilateral STN devices and stimulation.

Procedure: Deep Brain Stimulation Surgery (DBS)

STN-PPN DBS

EXPERIMENTAL

Patients will be implanted with both bilateral STN and bilateral PPN devices. These patients will undergo a crossover between 3 and 15 months post-op in which they will double-blindly receive PPN stimulation for six months and have stimulation turned off for six months. All patients will receive stimulation from 0-3 months post-op (mapping visits occur in this window) and from 15-27 months.

Device: STN-PPN DBS Surgery

Interventions

STN-PPN DBS Surgery DEVICE

Subject will undergo standard bilateral STN DBS surgery and have 2 additional leads placed in the same burr with bilateral PPN targets

STN-PPN DBS

Deep Brain Stimulation Surgery (DBS) PROCEDURE

DBS lead implantation of bilateral STN

STN DBS

Eligibility Criteria

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

You may qualify if:

• Informed consent signed by the subject.
• Diagnosed with Parkinson's disease per UK Parkinson's Disease Society Brain Bank (Queens Square) criteria for at least 4 years
• Demonstrates levodopa responsiveness of at least 30%
• Experiences tremor or motor complications including wearing off and/or dyskinesia
• DBS candidate per FDA guidelines as outlined in criteria 2-4
• Candidate for STN targeting per the consensus committee
• Subject exhibits gait instability, or a history of at least one fall within the last year, or a history of falls on tests of Static or Dynamic Stability.
• PD Stage 2-3 with predominant axial symptoms or FOG refractory to Levodopa \> 600 mg and UPDRS Part III Subscore of \>6.
• Subject is ambulatory and able to walk for limited periods of time without using an assistive device.
• years of age
• Primary English speaking
• Physically and cognitively capable of completing evaluations and consent
• Medically cleared for surgery and anesthesia
• Female subjects with child-bearing potential have a negative serum pregnancy test prior to DBS surgery

You may not qualify if:

• Dementia per DSM-V criteria
• Condition precluding MRI
• History of supraspinal CNS disease other than PD
• History of schizophrenia, delusions, or currently uncontrolled visual hallucinations
• Subjects who require rTMS, ECT, diathermy, or repeat MRI procedures to treat a medical condition.
• Subjects with a history of seizure disorder
• Subjects who have made a suicide attempt within the prior year,
• Subjects with any medical contraindications to undergoing DBS surgery (eg, infection, coagulopathy, or significant cardiac or other medical risk factors for surgery)
• Subjects with an implanted stimulator such as a cardiac pacemaker, defibrillator, neurostimulator and cochlear implant
• Subjects who are pregnant or nursing.
• Patient that is unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the protocol.
• Any other reasons that, in the opinion of the investigator, the candidate is determined to be unsuitable for entry into the study.

Sponsors & Collaborators

• St. Joseph's Hospital and Medical Center, Phoenix: lead
• Arizona State University: collaborator

Study Sites (1)

St. Joseph's Hospital & Medical Center / Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

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

Study Officials

• Guillermo Moguel-Cobos, MD

  Muhammad Ali Movement Disorders Clinic Physician

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomly assigned (1:1) to receive either traditional STN stimulation or STN+PPN patients. Once implanted, all patients will receive stimulation of all implanted devices for the first three months to allow for stimulation parameters to be adjusted. During this time, STN+PPN subjects will have their PPN stimulation parameters mapped (all DBS contacts in the PPN will be tested to determine which stimulation pattern achieves best results). Once patients have been tested at the 3-month post-op visit, STN+PPN patients will be double-blindly randomized (1:1) to either receive or not receive PPN stimulation for the following six months before further testing. Following the 9-month testing visit, STN+PPN patients will be crossed over so that those receiving PPN stimulation before will have their device turned off, and vice versa. After further testing at 15 months, all patients will have their devices turned back on. There will be one final test at 27 months.

Study Record Dates

• First Submitted: August 31, 2020
• First Posted: October 27, 2020
• Study Start: November 1, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)