Pedunculopontine Nucleus Stimulation for Gait Disorders in Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title:

Effects of Low Frequency Deep Brain Stimulation of the Pedunculopontine Nucleus on Gait and Balance Disorders of Parkinson's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02055261
• Other study ID #: RBM C08-07
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 16, 2014
• Last updated: February 3, 2014
• Start date: May 2009
• Est. completion date: May 2012

Study information

• Verified date: February 2014
• Source: Hôpital de la Salpétrière
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Device:
• Low frequency DBS of the pedunculopontine nucleus

Locations

Country	Name	City	State
France	Hôpital de la Pitié-Salpétrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Hôpital de la Salpétrière

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in sleep architecture between "off stim" and "on stim" conditions		4 and 6 months after surgery	Yes
Other	changes in cognitive evaluation between "Off stim" and 'On stim" conditions		4 and 6 months after surgery	Yes
Other	changes in cognitive evaluation between "No stim" and 'Off stim" conditions		1 month before surgery and 4 or 6 months after surgery	Yes
Other	changes in cognitive evaluation between "No stim" and 'On stim" conditions		1 month before surgery and 4 or 6 months after surgery	Yes
Primary	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	4 months and 6 months after surgery	No
Secondary	Adverse events records		1 month before surgery, 1-2-3-4-5-6 months after surgery	Yes
Secondary	Change of UPDRS part 3 score between "Off Stim Off drug" and "ON stim Off drug" conditions		4 and 6 months after surgery	No
Secondary	Change of Rating scale for gait evaluation between 'Off stim on drug" and "On stim on drug" conditions		4 and 6 months after surgery	No
Secondary	Change of UPDRS part 3 score between "Off Stim On drug" and "ON stim On drug" conditions		4 and 6 months after surgery	No
Secondary	Change of UPDRS part 3 score between "Off Stim Off drug" and "No stim Off drug" conditions		1 month before surgery and 4 or 6 months after surgery	No
Secondary	Change of UPDRS part 3 score between "Off Stim On drug" and "No stim On drug" conditions		1 month before surgery and 4 or 6 months after surgery	No
Secondary	Change of Rating scale for gait evaluation between 'Off stim Off drug" and "No stim off drug" conditions		1 month before surgery and 4 or 6 months after surgery	No
Secondary	Change of Rating scale for gait evaluation between 'Off stim On drug" and "No stim on drug" conditions		1 month before surgery and 4 or 6 months after surgery	No
Secondary	Change of Rating scale for gait evaluation between 'On stim Off drug" and "No stim off drug" conditions		1 month before surgery and 4 or 6 months after surgery	No
Secondary	Change of Rating scale for gait evaluation between 'On stim On drug" and "No stim On drug" conditions		1 month before surgery and 4 or 6 months after surgery	No
Secondary	Change of gait physiological parameters between "Off Stim Off drug" and "ON stim Off drug" conditions		4 and 6 months after surgery	No
Secondary	Change of gait physiological parameters between "Off Stim On drug" and "ON stim On drug" conditions		4 and 6 months after surgery	No
Secondary	Change of gait physiological parameters between "No Stim On drug" and "Off stim On drug" conditions		1 month before surgery and 4 or 6 months after surgery	No
Secondary	Change of gait physiological parameters between "No Stim Off drug" and "On stim off drug" conditions		1 month before surgery and 4 or 6 months after surgery	No
Secondary	Change of gait physiological parameters between "No Stim Off drug" and "Off stim off drug" conditions		1 month before surgery and 4 or 6 months after surgery	No