Safety and Efficacy of Motor Cortex Stimulation in the Treatment of Advanced Parkinson Disease

Parkinson Disease Clinical Trial

Official title:

Phase 1 Study of Motor Cortex Stimulation in the Treatment of Advanced Parkinson Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00159172
• Other study ID #: Parkostim
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: September 7, 2005
• Last updated: March 5, 2007
• Start date: September 2005
• Est. completion date: May 2008

Study information

• Verified date: September 2005
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Stephane Palfi, MD, PhD
• Phone: 33149812203
• Email: stephane.palfi[@]hmn.aphp.fr
• 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 purpose of this study is to determine whether motor cortex stimulation, a mildly invasive surgical procedure, is safe and effective in advanced stage Parkinsonian patients who display side effects with dopaminergic treatment.

Description:

Advanced stage of Parkinson disease (PD) is a difficult condition to treat, especially after several years of dopaminergic drugs. Recent development of neurosurgical techniques using deep brain stimulation leads has shown good behavioral results in these advanced PD patients. However, the placement of a stimulation lead in the subthalamic nucleus is a complex, invasive, and long surgical procedure. Such intervention requires a sophisticated technical environment, including a stereotactic magnetic resonance imaging (MRI) exam, associated with per-operative electrophysiological exploration of deep brain structures. This surgical treatment can therefore be indicated only for a few selected patients, and cannot be offered to a large proportion of patients among the potential candidates (estimation of 5000 patients in France). Thus, there is a need to develop therapeutic alternatives that would be technically and practically more convenient, less invasive, and that could be offered to a larger number of patients. Several clinical studies, including one led by our group, have already demonstrated that transcranial magnetic cortical stimulation could improve bradykinesia and shorten motor reaction time in patients with Parkinson disease. The clinical benefit was however moderate, and transient, probably because the stimulating sessions were too short in duration.

A prolonged effect could be obtained with continuous cortical stimulation. Such cortical stimulation has already been developed with good clinical tolerance in our hospital since 1991 for chronic neuropathic pain syndromes. In a non-human primate model of late stage Parkinson disease, we have recently demonstrated that prolonged primary motor cortex stimulation significantly improved both akinesia and bradykinesia.

The primary objective of this pilot study will be to evaluate the tolerance and efficacy of chronic stimulation of the primary motor cortex in 10 patients suffering from advanced stage Parkinson disease, despite the optimisation of dopaminergic treatment. The expected benefit for the patient will be gait improvement, increased movement velocities, and finally a better quality of life associated with reduction in dopaminergic medication and low per-operative morbidity risk.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age between 18 and 70 years

• Idiopathic Parkinson disease, for at least 5 years of evolution

• Asymmetric akinetic-rigid form, with symptoms predominant in the right side of the body (stimulator will be implanted on the left side).

• Functional impairment score in off stage (no drug treatment) of 3-4 according to the Hoehn and Yahr scale

• UPDRS III score > 40 in off-drug stage.

• UPDRS III score with L-dopa treatment improved by at least 50% compared to UPDRS III score in off-drug stage

Exclusion Criteria:

• Age superior to 70 years

• Adult patients under guardianship

• Previous neurosurgical operation(s)

• Previous partial or generalised seizures

• Mini Mental Status (MMS) score ? 24 or Mattis score < 130 or Montgomery-Asberg Depression Rating Scale (MADRS) depression score > 20.

• Presence of signal abnormalities on T1- and T2- MRI sequences

• Abnormalities in general exam or biological constants (hemogram, ionogram, hepatic or kidney dysfunction) with a higher surgical risk

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Educational/Counseling/Training

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Device:
• Motor cortex stimulation

Locations

Country	Name	City	State
France	Neurosurgical Department Henri Mondor Hospital	Creteil

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (1)

Drouot X, Oshino S, Jarraya B, Besret L, Kishima H, Remy P, Dauguet J, Lefaucheur JP, Dollé F, Condé F, Bottlaender M, Peschanski M, Kéravel Y, Hantraye P, Palfi S. Functional recovery in a primate model of Parkinson's disease following motor cortex stimulation. Neuron. 2004 Dec 2;44(5):769-78. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of the treatment and Unified Parkinson Disease Rating Scale (UPDRS) III 1 month following constant stimulation with and without motor cortex stimulation when the patient has no anti-parkinsonian drug for 12 hours
Secondary	Quality of life: Parkinson's Disease Questionnaire 39 (PDQ39) scores
Secondary	Anti-parkinsonian drug doses (equivalent L-dopa)
Secondary	Results of motor activation study in positron emission tomography (PET) scan
Secondary	Results of the different neuropsychological tests
Secondary	Video movement analysis