Transcranial Magnetic Stimulation to Treat Parkinson's Disease

Objective

To demonstrate cumulative and long-lasting improvement of parkinsonian symptoms by iTBS and its safety in PD patients.

Study population

Patients (40-80 years of age) with PD, Hoehn and Yahr disease stage of 2 to 4 while off, being on a regimen including levodopa with a total dose of medication equal to more than 300 mg of levodopa, including their dopamine agonist agents, and having problems with walking and needing 6 seconds or more to walk a 10-meter distance.

Design

Randomized, double-blind, placebo (sham)-controlled study. Enrollment of 30 patients with PD in 2 groups (real versus sham stimulation). Performance (8 interventions) of iTBS with large circular coil over motor and prefrontal cortex on both sides. Assessment with standard tests of motor function over a one-month period.

Outcome measure

The primary endpoint is change in gait speed as assessed by the time it takes to walk 10 m.

Secondary endpoints include changes in bradykinesia as assessed by measuring the time it takes to do ten combined hand and arm movements, and in total and motor UPDRS score.

• INCLUSION CRITERIA:
• Men and women aged 40 to 80 years with DOPA-responsive PD
• Hoehn and Yahr grade of 2 to 4 while off
• Must be on a regimen including levodopa.
• Total dose of levodopa and dopamine agonists (using dopamine equivalents) has to be equal to or more than 300 milligrams per day
• Problems with walking, including freezing gait time for a 10-meter distance greater than six seconds or more

Exclusion criteria

• Any active psychiatric disease or evidence of dementia
• History of seizures and epilepsy
• Concurrent use of tricyclic antidepressants, neuroleptic agents, or any other licit or illicit drugs other than anti-parkinsonian agents that could lower the seizure threshold except for SSRI
• Pallidotomy, implanted electrodes and generator for deep brain stimulation
• Pregnancy
• Surgically or traumatically implanted foreign bodies such as a pacemaker, implanted medical pump, implanted hearing aids, metal plate in the skull, or metal implant in the skull or eyes (other than dental appliances or fillings) that may pose a physical hazard during TEP.
• Study would cause undue risk or stress for reasons such as tendency to fall, excessive fatigue, general frailty, or excessive apprehensiveness.
• Dementia as assessed by the Folstein's Mini-Mental Test Examination (MMSE less than or equal to 24/30) or mentally impaired patients having no capacity to provide their own consent (the physician establishing the diagnosis and applying UPDRS will evaluate patient's mental capacity using conventional clinical interview)
• Unable to walk a 10-meter distance.
• More than occasional falls, i.e. daily falls (corresponding to a score greater than or equal to 3 and more in UPDRS item 13), history of fall(s) with significant injuries, absence of postural response in the on condition and/or spontaneous loss of balance in the off condition (corresponding to a score of greater than or equal to 2 and greater than or equal to 3 in on/off condition, respectively, in UPDRS item 30)

Pregnancy is unusual in patients with PD, grade 2-4. Urine sample for the pregnancy test will be obtained in patients of childbearing potential prior to the iTBS start, at the day of the initial interview and signing the consent form. Women of childbearing potential will be asked to take appropriate measures to prevent a pregnancy during the study.