50 Hz Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Parkinson's Disease

Controlled Study of 50 Hz Repetitive Transcranial Magnetic Stimulation for the Treatment of Parkinson's Disease

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00977184

Enrollment

Registered

2009-09-15

Start date

2009-09-30

Completion date

2010-07-31

Last updated

2012-12-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson Disease

Keywords

Parkinson's Disease, Transcranial Magnetic Stimulation (TMS), Treatment Study, PD, Parkinson Disease

Brief summary

Background: * In transcranial magnetic stimulation (TMS), a device creates a short-lasting magnetic field which induces an electric current in the brain leading to a change in the activity of brain cells. There are different effects on the brain with different rates of stimulation. In a previous study in people with Parkinson's disease, repetitive TMS (rTMS) given at a particular rate temporarily improved their ability to walk. A faster rate of rTMS may be more effective in treating symptoms than the rate originally used. * This study will compare active rTMS to inactive (sham or Placebo) rTMS. Half of the people in this study will have active rTMS; the other half will have no brain stimulation with rTMS. Objectives: \- To see if a faster rate of transcranial magnetic stimulation is a more effective treatment for the symptoms of Parkinson's disease than the slower rates that have been studied. Eligibility: * Individuals between 40 and 80 years of age who have been diagnosed with mild or moderate Parkinson's disease. * Participants must currently be taking Sinemet or dopamine agonists drugs (e.g., bromocriptine, cabergoline, pergolide, pramipexole, ropinirole, apomorophine, and rotigotine), and are willing to continue their same treatments for the duration of the study. Design: * This study requires 11 outpatient visits to the NIH Clinical Center over 6 weeks. Participants can also be admitted and stay as an inpatient in the NIH Clinical Center for the entire study period (for the 10 visits during the first weeks and the follow-up visit a month later). * Initial visit will consist of a physical examination; a test of participants' time to walk 10 meters; and questions about memory, mood, and quality of life. Participants should not take Parkinson's disease medications for 12 hours before this visit; once the examinations and tests are complete, participants will be able to take the medications. Researchers will repeat the tests 1 hour after participants take the medication. * TMS sessions: 8 TMS sessions (4 sessions per week) over 2 weeks. Each stimulation session will last half an hour. Half of the participants will receive active TMS; the other half will receive sham TMS. * The first 10 participants will have additional tests to study the safety of rapid TMS in patients with Parkinson's disease. * A day after completing the last TMS session, participants will repeat the same tests as the first visit before and after taking their medication as in the first assessment and respond to questions about mood, memory, and quality of life. * One month after completing the last TMS session, participants will repeat the same tests as the first visit before and after taking their medication.

Detailed description

Objective: To demonstrate cumulative and long-lasting improvement of parkinsonian symptoms by 50 Hz rTMS (repetitive transcranial magnetic stimulation) and its safety in Parkinson's Disease (PD) patients. Study population: Up to 30 PD patients in Hoehn and Yahr disease stage 2-4 while off medication will be enrolled. Patients must be receiving more than 300 mg of levodopa (including dopamine agonists) and have gait problems. Design: This is a randomized, double-blind, placebo (sham)-controlled study of 26 patients with PD in 2 groups (real versus sham stimulation). The study involves performance (8 interventions) of 50 Hz rTMS with large circular coil over the motor cortex on both sides of the brain. Assessment of PD symptoms with standard tests of motor function will be performed over a one-month period. Outcome measure: The primary endpoint include the changes in gait speed as assessed by the time it takes to walk 10 meters and the changes in bradykinesia as assessed by measuring the time it takes to do 10 combined hand and arm movements. Secondary endpoints include the changes in the total, motor and activities of daily living Unified Parkinson's Disease Rating Scale (UPDRS) score.

Interventions

PROCEDURE50 HZ Repetitive TMS

PROCEDURESham rTMS

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 80 Years

Healthy volunteers

Inclusion 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 and gait time for a 10-meter distance greater than six seconds or more

Exclusion criteria

Any active psychiatric disease 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 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 starting the 50 Hz rTMS and also at the initial interview after signing the consent form. Women of childbearing potential will be asked to take appropriate measures to prevent a pregnancy during the study.

Design outcomes

Primary

Measure	Time frame	Description
Gait Speed	Baseline, 1 day post rTMS	Gait speed was assessed by measuring the time it takes to walk 10 meters. Subject's gait speed was measured while on medication and off medication for each group, i.e., real rTMS and sham rTMS. Two trials were averaged for each condition. Patients were instructed to walk fast without taking the risk of falling, wearing the same shoes and consistently using assistive devices if needed. Gait speed was measured at baseline and 1 day post intervention.

Secondary

Measure	Time frame	Description
Bradykinesia	Baseline, 1 day post rTMS	Bradykinesia refers to the slowness in executing a movement. Bradykinesia was assessed by measuring the time in seconds it takes to do the following sequence, 10 times: 1) hand closing and opening while squeezing a ball 2) elbow flexion 3) hand closing and opening, and 4) elbow extension. Subjects were allowed to practice these hand and arm movements until performance appeared not to get faster, and then abstained from further practice to minimize learning effects. The time it takes subjects to execute the entire sequence 10 times with either the left or right arm/hand was measured. Means are reported for each group.
Total UPDRS Score	Baseline, 1 day post rTMS	The Total Unified Parkinson's Disease Rating Scale (UPDRS) is an overall assessment scale that quantifies the signs and symptoms of Parkinson's disease. The total UPDRS score consists of mentation, behavior, mood, activities of daily living and motor components, and ranges from 0 (not affected) to 176 (most severely affected). The total UPDRS score is obtained from patient examination, interview and patient questionnaires.
Motor UPDRS	Baseline, 1 day post rTMS	The Motor Unified Parkinson's Disease Rating Scale (UPDRS) includes only the motor assessment of the UPDRS (Part III) and examines speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability and body bradykinesia. The scores range from 0 (no motor impairment) to 108 (severe motor impairment). The Motor UPDRS was administered at baseline and at 1 day post rTMS or sham. Subjects were assessed on medication and off medication.
Activities of Daily Living UPDRS	Baseline, 1 day post rTMS	The Activities of Daily Living Unified Parkinson's Disease Rating Scale (ADL UPDRS) is a self evaluation of the activities of daily living. The following variables are rated: speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing, hygiene, turning in bed, falling, freezing when walking, walking, tremor and sensory complaints. Each variable is rated on a scale of 0 (normal) to 4 (severe impairment). A total score for the ADL UPDRS ranges from 0 (no impairment) to 52 (severe impairment).

Countries

United States

Participant flow

Participants by arm

Arm	Count
Real rTMS Subjects receiving real rTMS	13
Sham rTMS Subjects receiving sham rTMS.	13
Total	26

Baseline characteristics

Characteristic	Total	Real rTMS	Sham rTMS
Age Continuous	64.1 years STANDARD_DEVIATION 8.6	64.5 years STANDARD_DEVIATION 9.1	63.7 years STANDARD_DEVIATION 8.3
Duration of Disease	8.96 years STANDARD_DEVIATION 5.5	8.6 years STANDARD_DEVIATION 4.1	9.3 years STANDARD_DEVIATION 6.8
Dyskinesias Absence of dyskinesias	17 participants	9 participants	8 participants
Dyskinesias Presence of dyskinesias	9 participants	4 participants	5 participants
Falls Absence of falls	25 participants	12 participants	13 participants
Falls Presence of falls	1 participants	1 participants	0 participants
Fluctuations Absence of Fluctuations	11 participants	6 participants	5 participants
Fluctuations Presence of Fluctuations	15 participants	7 participants	8 participants
Gait freezing Absence of Gait Freezing	10 participants	6 participants	4 participants
Gait freezing Presence of Gait Freezing	16 participants	7 participants	9 participants
Hoehn-Yahr off	2.8 units on a scale STANDARD_DEVIATION 0.47	2.7 units on a scale STANDARD_DEVIATION 0.3	2.9 units on a scale STANDARD_DEVIATION 0.6
Hoehn-Yahr, on	2.42 units on a scale STANDARD_DEVIATION 0.27	2.4 units on a scale STANDARD_DEVIATION 0.2	2.5 units on a scale STANDARD_DEVIATION 0.3
Sex: Female, Male Female	6 Participants	2 Participants	4 Participants
Sex: Female, Male Male	20 Participants	11 Participants	9 Participants
Total LED	905 milligrams STANDARD_DEVIATION 559.6	861 milligrams STANDARD_DEVIATION 436	949 milligrams STANDARD_DEVIATION 677
Tremor Absence of Tremor	4 participants	3 participants	1 participants
Tremor Presence of Tremor	22 participants	10 participants	12 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	0 / 13	0 / 13	0 / 13	0 / 13
serious Total, serious adverse events	0 / 13	0 / 13	0 / 13	0 / 13

Outcome results

Primary

Gait Speed

Gait speed was assessed by measuring the time it takes to walk 10 meters. Subject's gait speed was measured while on medication and off medication for each group, i.e., real rTMS and sham rTMS. Two trials were averaged for each condition. Patients were instructed to walk fast without taking the risk of falling, wearing the same shoes and consistently using assistive devices if needed. Gait speed was measured at baseline and 1 day post intervention.