Clinical trial NCT00753519: Transcranial Magnetic Stimulation to Treat Parkinson's Disease
Official title: Intermittent Theta-Burst Transcranial Magnetic Stimulation (TBS) for the Treatment of Parkinson Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
Keywords: Parkinson's Disease
Brain Stimulation
Motor Cortex
Bradykinesia
Parkinson Disease
PD
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2008-09-16
Enrollment: 28
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will look at the effects of transcranial magnetic stimulation (TMS) on symptoms of Parkinson's disease. TMS is a method of brain stimulation that may be able to change the activity of the nerve cells of the brain. This study will examine the effects of a specific pattern of stimulation called intermittent theta-burst TMS (iTBS), which uses repeated magnetic pulses delivered in short bursts.

People with mild to moderately severe Parkinson's disease who are between 40 and 80 years of age and whose main problems are slow movement and stiffness may be eligible for this study.

Participants undergo the following tests and procedures:

* Random assignment to real or placebo (sham) iTBS treatment.
* iTBS sessions (real or sham) 4 times a week for 2 consecutive weeks. For this test, the subject sits in a comfortable chair. A wire coil is held on the subject's scalp, and a brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. The subject hears a click and may feel a pulling sensation on the skin under the coil. There may be a twitch in the muscles of the face, arm or leg.
* Test of gait (walk), hand and arm movements before and after each session. The gait test requires walking 10 meters (about 30 yards) in the same corridor with the same shoes.
* Extended testing. The first and last gait tests (done before starting iTBS and after the eighth session) require coming off any Parkinson's medication for at least 12 hours before the test. On these test days, subjects also undergo a clinical examination, short neuropsychological test battery, a computer-based reaction time test and depression and quality-of-life rating scales. These procedures are repeated in a follow-up visit 1 month after the last session.

Detailed description: 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.

Eligibility criteria: * 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.

Primary outcomes:
measure: Gait Speed
timeFrame: baseline, 1 day post iTBS
Secondary outcomes:
measure: Bradykinesia
timeFrame: baseline, 1 day post iTBS
measure: Total UPDRS Score
timeFrame: baseline, 1 day post iTBS
measure: Motor UPDRS
timeFrame: baseline, 1 day post iTBS
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
References:
citation: Aarsland D, Larsen JP, Waage O, Langeveld JH. Maintenance electroconvulsive therapy for Parkinson's disease. Convuls Ther. 1997 Dec;13(4):274-7.
citation: Baudewig J, Siebner HR, Bestmann S, Tergau F, Tings T, Paulus W, Frahm J. Functional MRI of cortical activations induced by transcranial magnetic stimulation (TMS). Neuroreport. 2001 Nov 16;12(16):3543-8. doi: 10.1097/00001756-200111160-00034.
citation: Belmaker RH, Grisaru N. Magnetic stimulation of the brain in animal depression models responsive to ECS. J ECT. 1998 Sep;14(3):194-205.