Pedunculopontine Nucleus Stimulation for Gait Disorders in Parkinson's Disease

NCT ID: NCT02055261

Last Updated: 2014-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2012-05-31

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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

OFF PPN DBS-ON PPN DBS

Patients randomly allocated to the order OFF Low frequency DBS of the pedunculopontine nucleus then ON Low frequency DBS of the pedunculopontine nucleus

Group Type: OTHER

Low frequency DBS of the pedunculopontine nucleus

Intervention Type: DEVICE

ON PPN DBS - OFF PPN DBS

Patients randomly allocated to the order ON Low frequency DBS of the pedunculopontine nucleus then OFF Low frequency DBS of the pedunculopontine nucleus

Group Type: OTHER

Low frequency DBS of the pedunculopontine nucleus

Intervention Type: DEVICE

Interventions

Low frequency DBS of the pedunculopontine nucleus

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pitié-Salpêtrière Hospital

OTHER

Sponsor Role: lead

Responsible Party

David Grabli

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hôpital de la Pitié-Salpétrière

Paris, , France

Countries

France

Other Identifiers

RBM C08-07

Identifier Type: -

Identifier Source: org_study_id