Clinical trial NCT04605263: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Parkinson Disease
Keywords: Deep Brain Simulation (DBS)
Gait and Balance
Postural Instability and Gait Dysfunction (PIGD)
Lead sponsor: St. Joseph's Hospital and Medical Center, Phoenix
Sponsor class: OTHER
Collaborators: name: Arizona State University
First posted: 2020-10-27
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: STN-PPN Stimulation Effect on Fall Risk
timeFrame: 27 months
Secondary outcomes:
measure: STN-PPN on Linear and Nonlinear Measures of Gait
timeFrame: 27 months
measure: STN-PPN on Linear and Nonlinear Measures of Balance
timeFrame: 27 months
measure: STN-PPN on Attention
timeFrame: 27 months
measure: STN-PPN on Subjective Measures of Alertness
timeFrame: 27 months
measure: STN-PPN on Subjective Measures of Sleep
timeFrame: 27 months
measure: STN-PPN on Subjective Measures of Non-Motor Symptoms
timeFrame: 27 months
measure: STN-PPN on Subjective Measures of Balance in Daily Life
timeFrame: 27 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital & Medical Center / Barrow Neurological Institute
state: Arizona
Study officials:
affiliation: Muhammad Ali Movement Disorders Clinic Physician
name: Guillermo Moguel-Cobos, MD
role: PRINCIPAL_INVESTIGATOR
References: