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

Parkinson Disease Clinical Trial

— PPNGB01  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04605263
• Other study ID #: PHX-19-500-412-30-04
• Status: Enrolling by invitation
• Phase: N/A
• Start date: November 1, 2021
• Est. completion date: September 1, 2025

Study information

• Verified date: November 2023
• Source: St. Joseph's Hospital and Medical Center, Phoenix
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 8
• Est. completion date: September 1, 2025
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

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

Locations

Country	Name	City	State
United States	St. Joseph's Hospital & Medical Center / Barrow Neurological Institute	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
St. Joseph's Hospital and Medical Center, Phoenix	Arizona State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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