Deep Brain Stimulation (DBS) of the Pedunculopontine Nucleus (PPN) (PPNGB01)

Effects of Deep Brain Stimulation (DBS) of the Pedunculopontine Nucleus (PPN) on Gait, Postural Stability, Freezing of Gait (FOG), and Falls

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Parkinson Disease
• Intervention / Treatment: Procedure: Deep Brain Stimulation Surgery (DBS); Device: STN-PPN DBS Surgery

Detailed Description

This is a prospective, single-center randomized controlled trial designed to estimate the potential clinical benefit, and associated risks, of deep brain stimulation of the of the PPN and STN in patients with PD that are candidates for DBS for improvement of their motor symptoms and exhibit gait instability with falls. Patients will be enrolled and implanted with additional bilateral electrodes in the PPN. Each subject will be randomized 1:1 to one of the following sequences: Bilateral STN+PPN stimulation or Bilateral STN stimulation alone. The addition of a bilateral STN stimulation only group allows for the research of potential micro-lesioning effects of the PPN which might affect features of interest even in the absence of PPN stimulation.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital & Medical Center / Barrow Neurological Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Inclusion Criteria

  1. Informed consent signed by the subject.
  2. Diagnosed with Parkinson's disease per UK Parkinson's Disease Society Brain Bank (Queens Square) criteria for at least 4 years
  3. Demonstrates levodopa responsiveness of at least 30%
  4. Experiences tremor or motor complications including wearing off and/or dyskinesia
  5. DBS candidate per FDA guidelines as outlined in criteria 2-4
  6. Candidate for STN targeting per the consensus committee
  7. 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.
  8. PD Stage 2-3 with predominant axial symptoms or FOG refractory to Levodopa > 600 mg and UPDRS Part III Subscore of >6.
  9. Subject is ambulatory and able to walk for limited periods of time without using an assistive device.
  10. 18-75 years of age
  11. Primary English speaking
  12. Physically and cognitively capable of completing evaluations and consent
  13. Medically cleared for surgery and anesthesia
  14. Female subjects with child-bearing potential have a negative serum pregnancy test prior to DBS surgery

Exclusion Criteria:

Exclusion Criteria:

1. Dementia per DSM-V criteria
2. Condition precluding MRI
3. History of supraspinal CNS disease other than PD
4. History of schizophrenia, delusions, or currently uncontrolled visual hallucinations
5. Subjects who require rTMS, ECT, diathermy, or repeat MRI procedures to treat a medical condition.
6. Subjects with a history of seizure disorder
7. Subjects who have made a suicide attempt within the prior year,
8. Subjects with any medical contraindications to undergoing DBS surgery (eg, infection, coagulopathy, or significant cardiac or other medical risk factors for surgery)
9. Subjects with an implanted stimulator such as a cardiac pacemaker, defibrillator, neurostimulator and cochlear implant
10. Subjects who are pregnant or nursing.
11. 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.
12. Any other reasons that, in the opinion of the investigator, the candidate is determined to be unsuitable for entry into the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: STN DBS; Subjects will receive traditional bilateral STN devices and stimulation.	Procedure: Deep Brain Stimulation Surgery (DBS); DBS lead implantation of bilateral STN
Experimental: STN-PPN DBS; 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; Subject will undergo standard bilateral STN DBS surgery and have 2 additional leads placed in the same burr with bilateral PPN targets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
STN-PPN on Linear and Nonlinear Measures of Gait	Linear and nonlinear measured of gait will be measured during straight walking, turning, and arising and returning to a chair.	27 months
STN-PPN on Linear and Nonlinear Measures of Balance	Linear and nonlinear measures of balance will be collected during eyes open, eyes closed, and perturbed (dyanic balance) conditions.	27 months
STN-PPN on Attention	The effect of PPN stimulation, in comparison to that of STN alone, on attention, with be measured using the Conners Continuous Auditory Test of Attention and Continuous Performance Test 3.	27 months
STN-PPN on Subjective Measures of Alertness	The effects of PPN stimulation on subjective function will be measured using the Toronto Alertness Scale, graded 0-50, with higher scores being better.	27 months
STN-PPN on Subjective Measures of Sleep	The effects of PPN stimulation on subjective function will be measured using the Epworth Sleep Scale, graded 0-24, with lower scores being better.	27 months
STN-PPN on Subjective Measures of Non-Motor Symptoms	The effects of PPN stimulation on subjective function will be measured using the Non-Motor Symptom Assessment, graded 0-360, with lower scores being better.	27 months
STN-PPN on Subjective Measures of Balance in Daily Life	The effects of PPN stimulation on subjective function will be measured using the Activity-specific Balance Confidence Scale, graded on a scale of 0-100, with higher scores being better.	27 months

Collaborators and Investigators

• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Collaborators: Arizona State University
• Investigators: Principal Investigator: Guillermo Moguel-Cobos, MD, Muhammad Ali Movement Disorders Clinic Physician

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: August 31, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (Actual): October 27, 2020

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Deep Brain Simulation (DBS); Gait and Balance; Postural Instability and Gait Dysfunction (PIGD)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: PHX-19-500-412-30-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is a Data Use Agreement (DUA), with Boston Scientific.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes