Pedunculopontine Nucleus Stimulation for Gait Disorders in Parkinson's Disease
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Low frequency DBS of the pedunculopontine nucleus
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease
Eligibility Criteria
Inclusion Criteria:
- Parkinson's disease
- Age < 70 and > = 18 years
- Improvement > or = 50 % during acute levodopa test
- Score > or = 2 on item 29 of UPDRS part 3 score obtained in "off" drug state
- No previous DBS
- No evidence of atypical parkinsonism
- No dementia (MATTIS > 129)
- No psychiatric disease
- Contraception if woman
- Informed consent
Exclusion Criteria:
- Contra indication to surgery
- Contra indication to MRI
- Severe life threatening comorbidity
Sites / Locations
- Hôpital de la Pitié-Salpétrière
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
OFF PPN DBS-ON PPN DBS
ON PPN DBS - OFF PPN DBS
Arm Description
Patients randomly allocated to the order OFF Low frequency DBS of the pedunculopontine nucleus then ON Low frequency DBS of the pedunculopontine nucleus
Patients randomly allocated to the order ON Low frequency DBS of the pedunculopontine nucleus then OFF Low frequency DBS of the pedunculopontine nucleus
Outcomes
Primary Outcome Measures
Change of Rating scale for gait evaluation between 'Off stim off drug" and "On stim off drug" conditions
The primary outcome criteria will be the comparison between RSGE total score in obtained 'Off' and 'On' stimulation conditions either at 4 or 6 months after surgery according to the randomized order of the cross-over
Secondary Outcome Measures
Adverse events records
Change of UPDRS part 3 score between "Off Stim Off drug" and "ON stim Off drug" conditions
Change of Rating scale for gait evaluation between 'Off stim on drug" and "On stim on drug" conditions
Change of UPDRS part 3 score between "Off Stim On drug" and "ON stim On drug" conditions
Change of UPDRS part 3 score between "Off Stim Off drug" and "No stim Off drug" conditions
Change of UPDRS part 3 score between "Off Stim On drug" and "No stim On drug" conditions
Change of Rating scale for gait evaluation between 'Off stim Off drug" and "No stim off drug" conditions
Change of Rating scale for gait evaluation between 'Off stim On drug" and "No stim on drug" conditions
Change of Rating scale for gait evaluation between 'On stim Off drug" and "No stim off drug" conditions
Change of Rating scale for gait evaluation between 'On stim On drug" and "No stim On drug" conditions
Change of gait physiological parameters between "Off Stim Off drug" and "ON stim Off drug" conditions
Change of gait physiological parameters between "Off Stim On drug" and "ON stim On drug" conditions
Change of gait physiological parameters between "No Stim On drug" and "Off stim On drug" conditions
Change of gait physiological parameters between "No Stim Off drug" and "On stim off drug" conditions
Change of gait physiological parameters between "No Stim Off drug" and "Off stim off drug" conditions
Full Information
NCT ID
NCT02055261
First Posted
January 16, 2014
Last Updated
February 3, 2014
Sponsor
Pitié-Salpêtrière Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02055261
Brief Title
Pedunculopontine Nucleus Stimulation for Gait Disorders in Parkinson's Disease
Official Title
Effects of Low Frequency Deep Brain Stimulation of the Pedunculopontine Nucleus on Gait and Balance Disorders of Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Pitié-Salpêtrière Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The appearance of postural instability and gait disorders is a major turning point in the evolution of Parkinson's disease (PD). These axial symptoms are usually unresponsive to L-Dopa and represent a severe impairment for the patients due to frequent falls and reduced outside mobility. There is no effective pharmacological treatment available for these symptoms, and their pathophysiology is not well known : it is currently assumed that non-dopaminergic brainstem lesions participate to axial symptoms in PD. Surgically, these patients cannot benefit from high frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) since this operation tends to even aggravate axial symptoms unresponsive to L-Dopa in some patients. A dysfunction of the pedunculopontine nucleus (PPN) might be at the origin of these axial symptoms, since the PPN participates in the maintenance of posture and motion in primates. In PD patients, recent reports have suggested that low frequency stimulation of the PPN may equally improve gait and posture. However, these results are debatable due to methodological limitations, insufficient clinical evaluation and uncertain anatomical targeting. Thus, our aim is to propose a low frequency PPN stimulation to six advanced PD patients according to the usual criteria for STN DBS who are, however, unsuitable for this operation due to gait and posture disorders. We will perform a randomized, double-blind and cross over design (two months periods with and without DBS randomly assigned to each patient). The targeting will be allowed by a a three-dimensional and deformable atlas of the basal ganglia fusioned with the stereotaxic magnetic resonance imaging (MRI) of each patient. Evaluations will comprise 1 month before surgery and in "Off" and "On" stimulation condition:
clinical motor assessment in both "Off" and "On" drug state, including cardinal parkinsonian signs, gait and balance
gait initiation physiological evaluation
cognitive and behavioral testing If our hypothesis is confirmed, low frequency PPN stimulation may well represent a substantial improvement of our therapeutic options for advanced PD patients suffering from debilitating gait and posture disorders unresponsive to L-Dopa.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
OFF PPN DBS-ON PPN DBS
Arm Type
Other
Arm Description
Patients randomly allocated to the order OFF Low frequency DBS of the pedunculopontine nucleus then ON Low frequency DBS of the pedunculopontine nucleus
Arm Title
ON PPN DBS - OFF PPN DBS
Arm Type
Other
Arm Description
Patients randomly allocated to the order ON Low frequency DBS of the pedunculopontine nucleus then OFF Low frequency DBS of the pedunculopontine nucleus
Intervention Type
Device
Intervention Name(s)
Low frequency DBS of the pedunculopontine nucleus
Primary Outcome Measure Information:
Title
Change of Rating scale for gait evaluation between 'Off stim off drug" and "On stim off drug" conditions
Description
The primary outcome criteria will be the comparison between RSGE total score in obtained 'Off' and 'On' stimulation conditions either at 4 or 6 months after surgery according to the randomized order of the cross-over
Time Frame
4 months and 6 months after surgery
Secondary Outcome Measure Information:
Title
Adverse events records
Time Frame
1 month before surgery, 1-2-3-4-5-6 months after surgery
Title
Change of UPDRS part 3 score between "Off Stim Off drug" and "ON stim Off drug" conditions
Time Frame
4 and 6 months after surgery
Title
Change of Rating scale for gait evaluation between 'Off stim on drug" and "On stim on drug" conditions
Time Frame
4 and 6 months after surgery
Title
Change of UPDRS part 3 score between "Off Stim On drug" and "ON stim On drug" conditions
Time Frame
4 and 6 months after surgery
Title
Change of UPDRS part 3 score between "Off Stim Off drug" and "No stim Off drug" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
Title
Change of UPDRS part 3 score between "Off Stim On drug" and "No stim On drug" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
Title
Change of Rating scale for gait evaluation between 'Off stim Off drug" and "No stim off drug" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
Title
Change of Rating scale for gait evaluation between 'Off stim On drug" and "No stim on drug" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
Title
Change of Rating scale for gait evaluation between 'On stim Off drug" and "No stim off drug" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
Title
Change of Rating scale for gait evaluation between 'On stim On drug" and "No stim On drug" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
Title
Change of gait physiological parameters between "Off Stim Off drug" and "ON stim Off drug" conditions
Time Frame
4 and 6 months after surgery
Title
Change of gait physiological parameters between "Off Stim On drug" and "ON stim On drug" conditions
Time Frame
4 and 6 months after surgery
Title
Change of gait physiological parameters between "No Stim On drug" and "Off stim On drug" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
Title
Change of gait physiological parameters between "No Stim Off drug" and "On stim off drug" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
Title
Change of gait physiological parameters between "No Stim Off drug" and "Off stim off drug" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
Other Pre-specified Outcome Measures:
Title
Changes in sleep architecture between "off stim" and "on stim" conditions
Time Frame
4 and 6 months after surgery
Title
changes in cognitive evaluation between "Off stim" and 'On stim" conditions
Time Frame
4 and 6 months after surgery
Title
changes in cognitive evaluation between "No stim" and 'Off stim" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
Title
changes in cognitive evaluation between "No stim" and 'On stim" conditions
Time Frame
1 month before surgery and 4 or 6 months after surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Parkinson's disease
Age < 70 and > = 18 years
Improvement > or = 50 % during acute levodopa test
Score > or = 2 on item 29 of UPDRS part 3 score obtained in "off" drug state
No previous DBS
No evidence of atypical parkinsonism
No dementia (MATTIS > 129)
No psychiatric disease
Contraception if woman
Informed consent
Exclusion Criteria:
Contra indication to surgery
Contra indication to MRI
Severe life threatening comorbidity
Facility Information:
Facility Name
Hôpital de la Pitié-Salpétrière
City
Paris
ZIP/Postal Code
75013
Country
France
12. IPD Sharing Statement
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Pedunculopontine Nucleus Stimulation for Gait Disorders in Parkinson's Disease
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