Pedunculopontine Nucleus Stimulation for Gait Disorders in Parkinson's Disease

NCT02055261 | Completed Phase 1 DMC

• 1 other identifier: RBM C08-07
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (15)

• Adverse events records

  1 month before surgery, 1-2-3-4-5-6 months after surgery

• Change of UPDRS part 3 score between "Off Stim Off drug" and "ON stim Off drug" conditions

  4 and 6 months after surgery

• Change of Rating scale for gait evaluation between 'Off stim on drug" and "On stim on drug" conditions

  4 and 6 months after surgery

• Change of UPDRS part 3 score between "Off Stim On drug" and "ON stim On drug" conditions

  4 and 6 months after surgery

• 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

Other Outcomes (4)

• Changes in sleep architecture between "off stim" and "on stim" conditions

  4 and 6 months after surgery

• changes in cognitive evaluation between "Off stim" and 'On stim" conditions

  4 and 6 months after surgery

• changes in cognitive evaluation between "No stim" and 'Off stim" conditions

  1 month before surgery and 4 or 6 months after surgery

Study Arms (2)

OFF PPN DBS-ON PPN DBS

OTHER

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

Device: Low frequency DBS of the pedunculopontine nucleus

ON PPN DBS - OFF PPN DBS

OTHER

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

Device: Low frequency DBS of the pedunculopontine nucleus

Interventions

Low frequency DBS of the pedunculopontine nucleus DEVICE

OFF PPN DBS-ON PPN DBS; ON PPN DBS - OFF PPN DBS

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Contra indication to surgery
• Contra indication to MRI
• Severe life threatening comorbidity

Sponsors & Collaborators

• Pitié-Salpêtrière Hospital: lead

Study Sites (1)

Hôpital de la Pitié-Salpétrière

Paris, 75013, France

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: January 16, 2014
• First Posted: February 5, 2014
• Study Start: May 1, 2009
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: February 5, 2014

Record last verified: 2014-02

Locations

FR (1)