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

Official title

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

Overview

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.

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.

Interventions

• 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
• Procedure Deep Brain Stimulation Surgery (DBS)
  DBS lead implantation of bilateral STN

Primary outcome measures

• STN-PPN Stimulation Effect on Fall Risk [Time frame: 27 months]

Secondary outcome measures (7)

• STN-PPN on Linear and Nonlinear Measures of Gait [Time frame: 27 months]
• STN-PPN on Linear and Nonlinear Measures of Balance [Time frame: 27 months]
• STN-PPN on Attention [Time frame: 27 months]
• STN-PPN on Subjective Measures of Alertness [Time frame: 27 months]
• STN-PPN on Subjective Measures of Sleep [Time frame: 27 months]
• STN-PPN on Subjective Measures of Non-Motor Symptoms [Time frame: 27 months]
• STN-PPN on Subjective Measures of Balance in Daily Life [Time frame: 27 months]

Eligibility criteria

Inclusion criteria

• Inclusion Criteria

• 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.
• 18-75 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

Exclusion criteria

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

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

Identifiers

NCT: NCT04605263 · PHX-19-500-412-30-04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗