Back to resultsDeep Brain Stimulation (DBS) of the Pedunculopontine Nucleus (PPN) (PPNGB01)
Primary Purpose
Parkinson Disease
Status
Enrolling by invitation
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
STN-PPN DBS Surgery
Deep Brain Stimulation Surgery (DBS)
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease focused on measuring Deep Brain Simulation (DBS), Gait and Balance, Postural Instability and Gait Dysfunction (PIGD)
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.
Sites / Locations
- St. Joseph's Hospital & Medical Center / Barrow Neurological Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
STN DBS
STN-PPN DBS
Arm Description
Subjects will receive traditional bilateral STN devices and stimulation.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT04605263
First Posted
August 31, 2020
Last Updated
May 5, 2022
Sponsor
St. Joseph's Hospital and Medical Center, Phoenix
Collaborators
Arizona State University
1. Study Identification
Unique Protocol Identification Number
NCT04605263
Brief Title
Deep Brain Stimulation (DBS) of the Pedunculopontine Nucleus (PPN)
Acronym
PPNGB01
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
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Enrolling by invitation
Study Start Date
November 1, 2021 (Actual)
Primary Completion Date
September 1, 2024 (Anticipated)
Study Completion Date
September 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Joseph's Hospital and Medical Center, Phoenix
Collaborators
Arizona State University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
Deep Brain Simulation (DBS), Gait and Balance, Postural Instability and Gait Dysfunction (PIGD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
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.
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
8 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
STN DBS
Arm Type
Active Comparator
Arm Description
Subjects will receive traditional bilateral STN devices and stimulation.
Arm Title
STN-PPN DBS
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
STN-PPN DBS Surgery
Intervention Description
Subject will undergo standard bilateral STN DBS surgery and have 2 additional leads placed in the same burr with bilateral PPN targets
Intervention Type
Procedure
Intervention Name(s)
Deep Brain Stimulation Surgery (DBS)
Intervention Description
DBS lead implantation of bilateral STN
Primary Outcome Measure Information:
Title
STN-PPN Stimulation Effect on Fall Risk
Description
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.
Time Frame
27 months
Secondary Outcome Measure Information:
Title
STN-PPN on Linear and Nonlinear Measures of Gait
Description
Linear and nonlinear measured of gait will be measured during straight walking, turning, and arising and returning to a chair.
Time Frame
27 months
Title
STN-PPN on Linear and Nonlinear Measures of Balance
Description
Linear and nonlinear measures of balance will be collected during eyes open, eyes closed, and perturbed (dyanic balance) conditions.
Time Frame
27 months
Title
STN-PPN on Attention
Description
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.
Time Frame
27 months
Title
STN-PPN on Subjective Measures of Alertness
Description
The effects of PPN stimulation on subjective function will be measured using the Toronto Alertness Scale, graded 0-50, with higher scores being better.
Time Frame
27 months
Title
STN-PPN on Subjective Measures of Sleep
Description
The effects of PPN stimulation on subjective function will be measured using the Epworth Sleep Scale, graded 0-24, with lower scores being better.
Time Frame
27 months
Title
STN-PPN on Subjective Measures of Non-Motor Symptoms
Description
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.
Time Frame
27 months
Title
STN-PPN on Subjective Measures of Balance in Daily Life
Description
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.
Time Frame
27 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillermo Moguel-Cobos, MD
Organizational Affiliation
Muhammad Ali Movement Disorders Clinic Physician
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Joseph's Hospital & Medical Center / Barrow Neurological Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
There is a Data Use Agreement (DUA), with Boston Scientific.
Learn more about this trial
Deep Brain Stimulation (DBS) of the Pedunculopontine Nucleus (PPN)
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