TMS: Transcranial Magnetic Stimulation in Spino-Cerebellar Ataxia

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01975909
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Spinocerebellar Ataxia (SCA) refers to a family of genetic diseases that cause progressive problems with gait and balance, as well as other debilitating symptoms. This is a randomized controlled pilot study to test a novel therapeutic intervention that uses noninvasive magnetic brain stimulation to improve functional outcomes in patients with SCA. The study will include quantitative evaluations of gait, balance, and brain physiology to examine possible objective end-points for a future, larger multi-site clinical trial. The investigators anticipate that patients receiving the real intervention will show a functional gain.

Condition or Disease	Intervention/Treatment	Phase
Spinocerebellar Ataxia	Device: Transcranial Magnetic Stimulation	N/A

Detailed Description

Spinocerebellar Ataxia (SCA) refers to a family of genetic diseases that cause progressive problems with gait and balance, as well as other debilitating symptoms. There is no cure for SCA and a lack of an effective symptomatic treatment.

Investigators will recruit 20 patients with genetically-confirmed SCA to use a novel approach

• noninvasive transcranial magnetic stimulation (TMS) - to improve balance, gait, and posture in patients with SCA. Half will be randomly assigned to a real intervention, and half to a sham (control) intervention. The TMS intervention will consist of 20 stimulation sessions over a four week period. At baseline and follow-up, patients will undergo comprehensive assessments including several SCA rating scales, along with sophisticated tests of balance (ie. walking, standing, and muscle coordination). Patients will also complete a series of neurophysiologic tests to evaluate the function of the cerebellum and its connections before and after the intervention.

Investigators anticipate patients receiving real TMS will show better balance, fewer falls, and improved mobility, while those undergoing sham stimulation will show no benefits. If our prediction is correct, this study will provide evidence-based support for a new treatment to improve the lives of patients with SCA.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Transcranial Magnetic Stimulation (TMS) in Spino-Cerebellar Ataxia
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Transcranial Magnetic Stimulation (TMS) A Magstim 200 (Magstim, UK) and 14cm circular coil positioned tangential to the head will be used to deliver stimuli at 100% of maximum stimulator output. Transcranial Magnetic Stimulation will be applied to three regions: 1) 4cm lateral to the right of the inion, 2) centered on the inion, 3) 4cm lateral to the left of the inion. Five pulses separated by 6 seconds will be delivered with a counter-clockwise current, followed by the same five pulses delivered with a clockwise current, for a total of 10 pulses per region, and 30 pulses per session.	Device: Transcranial Magnetic Stimulation; 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.; Other Names: Magstim 200
Sham Comparator: Sham Transcranial Magnetic Stimulation A sham condition of Transcranial Magnetic Stimulation will be used and follow the same protocol as the active stimulation; however no magnetic pulses will be delivered through the scalp.	Device: Transcranial Magnetic Stimulation; 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.; Other Names: Magstim 200

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline to Post Treatment on the Scale for the Assessment and Rating of Ataxia (SARA) [Baseline and 1 week post treatment]

   Assess 8 items: gait, stance, sitting, speech, dysmetria, kinetic tremor, pro- and supinations of the hand, and the heel-shin slide. Each item is scored by the physician on a 4 to 8 numerical scale based upon the amount of dysfunction observed while performing the task. The maximum possible score for the total scale is 40. Lower scores of SARA represents better task performance.

Secondary Outcome Measures

1. Percent Change From Baseline to Post Treatment on the Timed 25-Foot Walk [Baseline and 1 week post treatment]

   A quantitative assessment of mobility and leg function. Two trials of patients walking along a 25ft course as quickly and safely as possible. Time taken to complete course will be recorded and averaged across trials.

2. Percent Change From Baseline to Post Treatment on the 9-hole Peg Test [Baseline and 1 week post treatment]

   The test consists of a block with nine holes, into which the subject places and then removes 9 pegs. The time taken to complete the test will be recorded.

Other Outcome Measures

1. Percent Change From Baseline to Post Treatment on Gait Speed in 90 Second Walking Test [Baseline and 1 week post treatment]

   Two 90 second trials of walking at a preferred speed along a 80x4m indoor hallway. A wireless Noraxon DTS system (Noraxon Inc, Scottsdale, AZ) will be used simultaneously and continuously record bilateral foot placements, 3-dimensional trunk accelerations, and lower-extremity surface electromyography of eight muscles.

2. Percent Change From Baseline to Post Treatment on Standing Postural Control [Baseline and 1 week post treatment]

   Postural control - assessed by measuring standing postural sway (ie., center-of pressure fluctuations) during two, 30second trials of standing with eyes open on a stationary force platform (AMTI, Watertown, MA).

3. Percent Change From Baseline to Post Treatment on Mobility and Turning [Baseline and 1 week post treatment]

   Mobility and turning is assessed by the timed up-and-go test (Podsiadlo & Richardson, 1991). The participant will be seated in an armed chair. On the word "go," the subject will stand up using the arm rests if needed, walk (with assistive device if needed) around a cone placed three meters in front of the chair, return and sit down as quickly as possible.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatients with ataxia as diagnosed by a movement disorder specialist and confirmed by clinically obtained genetic testing of the patient and/or in a first-degree relative of the patient.

• Women of child-bearing potential must use a reliable method of contraception and must provide a negative pregnancy test at entry into the study

• Stable on doses of all medications for at least 30 days prior to study entry and for the duration of the study

• The ability to ambulate

• A score of three or higher (worse) on the 'gait' subsection of the Scale of the Assessment and Rating of Ataxia (SARA) rating scale.

Exclusion Criteria:

• Any unstable illness or concomitant medical condition that, in the investigator's opinion, precludes participation in this study, including disorders that may affect gait or balance (i.e., stroke, arthritis, etc).

• The presence of clinically significant abnormalities on screening CBC, CMP or EKG.

• Pregnancy or lactation

• Concurrent participation in another clinical study

• A history of substance abuse

• The presence of psychosis, bipolar disorder, untreated depression (BDI greater than or equal to 21), or history of suicide attempt.

• Dementia or other psychiatric illness that prevents the patient from giving informed consent (Mini Mental Status Exam score less than 24).

• Legal incapacity or limited legal capacity.

• Ataxia derived from any cause other than genetically-confirmed SCA (including but not limited to alcoholism, head injury, Multiple Sclerosis, olivo-ponto-cerebellar atrophy or multiple system atrophy).

• No medication is an absolute exclusion from TMS. Medications will be reviewed by the responsible MD and a decision about inclusion will be made based on the following:

1. The patient's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other CNS active drugs.

2. The published TMS guidelines review of medications to be considered with TMS.

• History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG.

• TMS and MRI-Specific exclusion criteria including:

1. Known metal in the head (such as a surgical aneurysm clip) or a history of prior neurosurgical procedures.

2. Ferromagnetic bioimplants activated by any electronic, mechanical or magnetic means, such as cochlear implants, pacemakers, medication pumps, vagal stimulators, deep brain stimulators, neurostimulators, biostimulators, or ventriculo-peritoneal shunts.

3. Subjects who have or might have bullet fragments or other shrapnel (veterans or workers exposed to metal in their work environment).

4. Subjects with metallic paint (e.g. color contact lenses, tattoos, metallic eyeliner)

5. Subjects expressing significant claustrophobia.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Alvaro Pascual-Leone, MD, PhD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Information on TMS and the lab conducting the study
• Information on Ataxia

Publications

None provided.

• Responsible Party: Alvaro Pascual-Leone, Professor of Neurology, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01975909
• Other Study ID Numbers: 2013P000233; 1R21NS085491-01
• First Posted: Nov 5, 2013
• Last Update Posted: May 30, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Alvaro Pascual-Leone, Professor of Neurology, Beth Israel Deaconess Medical Center: Spinocerebellar Ataxia; SCA; Ataxia; Transcranial Magnetic Stimulation; TMS
• Additional relevant MeSH terms: Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations

Study Results

Participant Flow

Arm/Group Title	Transcranial Magnetic Stimulation (TMS)	Sham Transcranial Magnetic Stimulation
Arm/Group Description	A Magstim 200 (Magstim, UK) and 14cm circular coil positioned tangential to the head will be used to deliver stimuli at 100% of maximum stimulator output. Transcranial Magnetic Stimulation will be applied to three regions: 1) 4cm lateral to the right of the inion, 2) centered on the inion, 3) 4cm lateral to the left of the inion. Five pulses separated by 6 seconds will be delivered with a counter-clockwise current, followed by the same five pulses delivered with a clockwise current, for a total of 10 pulses per region, and 30 pulses per session. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.	A sham condition of Transcranial Magnetic Stimulation will be used and follow the same protocol as the active stimulation; however no magnetic pulses will be delivered through the scalp. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.
Period Title: Overall Study
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Transcranial Magnetic Stimulation (TMS)	Sham Transcranial Magnetic Stimulation	Total
Arm/Group Description	A Magstim 200 (Magstim, UK) and 14cm circular coil positioned tangential to the head will be used to deliver stimuli at 100% of maximum stimulator output. Transcranial Magnetic Stimulation will be applied to three regions: 1) 4cm lateral to the right of the inion, 2) centered on the inion, 3) 4cm lateral to the left of the inion. Five pulses separated by 6 seconds will be delivered with a counter-clockwise current, followed by the same five pulses delivered with a clockwise current, for a total of 10 pulses per region, and 30 pulses per session. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.	A sham condition of Transcranial Magnetic Stimulation will be used and follow the same protocol as the active stimulation; however no magnetic pulses will be delivered through the scalp. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.	Total of all reporting groups
Overall Participants	10	10	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.3 (10.1)	48.6 (4.8)	50.6 (7.5)
Sex: Female, Male (Count of Participants)
Female	8 80%	8 80%	16 80%
Male	2 20%	2 20%	4 20%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline to Post Treatment on the Scale for the Assessment and Rating of Ataxia (SARA)
Description	Assess 8 items: gait, stance, sitting, speech, dysmetria, kinetic tremor, pro- and supinations of the hand, and the heel-shin slide. Each item is scored by the physician on a 4 to 8 numerical scale based upon the amount of dysfunction observed while performing the task. The maximum possible score for the total scale is 40. Lower scores of SARA represents better task performance.
Time Frame	Baseline and 1 week post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcranial Magnetic Stimulation (TMS)	Sham Transcranial Magnetic Stimulation
Arm/Group Description	A Magstim 200 (Magstim, UK) and 14cm circular coil positioned tangential to the head will be used to deliver stimuli at 100% of maximum stimulator output. Transcranial Magnetic Stimulation will be applied to three regions: 1) 4cm lateral to the right of the inion, 2) centered on the inion, 3) 4cm lateral to the left of the inion. Five pulses separated by 6 seconds will be delivered with a counter-clockwise current, followed by the same five pulses delivered with a clockwise current, for a total of 10 pulses per region, and 30 pulses per session. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.	A sham condition of Transcranial Magnetic Stimulation will be used and follow the same protocol as the active stimulation; however no magnetic pulses will be delivered through the scalp. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.
Measure Participants	10	10
Mean (Standard Deviation) [percentage change]	-25.9 (16.4)	-27.8 (9.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transcranial Magnetic Stimulation (TMS), Sham Transcranial Magnetic Stimulation
	Comments
	Type of Statistical Test	Equivalence
	Comments	We hypothesized that the real TMS would improve the performance of SARA (i.e., greater percent decrease of SARA score from baseline) as compared to the sham TMS.
Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Percent Change From Baseline to Post Treatment on the Timed 25-Foot Walk
Description	A quantitative assessment of mobility and leg function. Two trials of patients walking along a 25ft course as quickly and safely as possible. Time taken to complete course will be recorded and averaged across trials.
Time Frame	Baseline and 1 week post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcranial Magnetic Stimulation (TMS)	Sham Transcranial Magnetic Stimulation
Arm/Group Description	A Magstim 200 (Magstim, UK) and 14cm circular coil positioned tangential to the head will be used to deliver stimuli at 100% of maximum stimulator output. Transcranial Magnetic Stimulation will be applied to three regions: 1) 4cm lateral to the right of the inion, 2) centered on the inion, 3) 4cm lateral to the left of the inion. Five pulses separated by 6 seconds will be delivered with a counter-clockwise current, followed by the same five pulses delivered with a clockwise current, for a total of 10 pulses per region, and 30 pulses per session. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.	A sham condition of Transcranial Magnetic Stimulation will be used and follow the same protocol as the active stimulation; however no magnetic pulses will be delivered through the scalp. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.
Measure Participants	10	10
Mean (Standard Deviation) [percentage change of maximum gait speed]	7.8 (12.0)	2.2 (25.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transcranial Magnetic Stimulation (TMS), Sham Transcranial Magnetic Stimulation
	Comments
	Type of Statistical Test	Equivalence
	Comments	We hypothesized that the real TMS would improve the performance of 25-foot walking test (i.e., greater percent increase of walking speed from baseline) as compared to the sham TMS.
Statistical Test of Hypothesis	p-Value	0.47
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Percent Change From Baseline to Post Treatment on the 9-hole Peg Test
Description	The test consists of a block with nine holes, into which the subject places and then removes 9 pegs. The time taken to complete the test will be recorded.
Time Frame	Baseline and 1 week post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcranial Magnetic Stimulation (TMS)	Sham Transcranial Magnetic Stimulation
Arm/Group Description	A Magstim 200 (Magstim, UK) and 14cm circular coil positioned tangential to the head will be used to deliver stimuli at 100% of maximum stimulator output. Transcranial Magnetic Stimulation will be applied to three regions: 1) 4cm lateral to the right of the inion, 2) centered on the inion, 3) 4cm lateral to the left of the inion. Five pulses separated by 6 seconds will be delivered with a counter-clockwise current, followed by the same five pulses delivered with a clockwise current, for a total of 10 pulses per region, and 30 pulses per session. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.	A sham condition of Transcranial Magnetic Stimulation will be used and follow the same protocol as the active stimulation; however no magnetic pulses will be delivered through the scalp. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.
Measure Participants	10	10
Mean (Standard Deviation) [percentage change]	0.7 (5.1)	-6.7 (7.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transcranial Magnetic Stimulation (TMS), Sham Transcranial Magnetic Stimulation
	Comments
	Type of Statistical Test	Equivalence
	Comments	We hypothesized that the real TMS would improve the performance of 9-hole peg test (i.e., greater percent decrease of time to complete the test from baseline) as compared to the sham TMS.
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	t-test, 2 sided
	Comments

4. Other Pre-specified Outcome

Title	Percent Change From Baseline to Post Treatment on Gait Speed in 90 Second Walking Test
Description	Two 90 second trials of walking at a preferred speed along a 80x4m indoor hallway. A wireless Noraxon DTS system (Noraxon Inc, Scottsdale, AZ) will be used simultaneously and continuously record bilateral foot placements, 3-dimensional trunk accelerations, and lower-extremity surface electromyography of eight muscles.
Time Frame	Baseline and 1 week post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcranial Magnetic Stimulation (TMS)	Sham Transcranial Magnetic Stimulation
Arm/Group Description	A Magstim 200 (Magstim, UK) and 14cm circular coil positioned tangential to the head will be used to deliver stimuli at 100% of maximum stimulator output. Transcranial Magnetic Stimulation will be applied to three regions: 1) 4cm lateral to the right of the inion, 2) centered on the inion, 3) 4cm lateral to the left of the inion. Five pulses separated by 6 seconds will be delivered with a counter-clockwise current, followed by the same five pulses delivered with a clockwise current, for a total of 10 pulses per region, and 30 pulses per session. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.	A sham condition of Transcranial Magnetic Stimulation will be used and follow the same protocol as the active stimulation; however no magnetic pulses will be delivered through the scalp. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.
Measure Participants	10	10
Mean (Standard Deviation) [percentage change]	4.2 (17.9)	5.3 (13.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transcranial Magnetic Stimulation (TMS), Sham Transcranial Magnetic Stimulation
	Comments
	Type of Statistical Test	Equivalence
	Comments	We hypothesized that the real TMS would improve the performance of 90-second walking test (i.e., greater percent increase of walking speed from baseline) as compared to the sham TMS.
Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	t-test, 2 sided
	Comments

5. Other Pre-specified Outcome

Title	Percent Change From Baseline to Post Treatment on Standing Postural Control
Description	Postural control - assessed by measuring standing postural sway (ie., center-of pressure fluctuations) during two, 30second trials of standing with eyes open on a stationary force platform (AMTI, Watertown, MA).
Time Frame	Baseline and 1 week post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcranial Magnetic Stimulation (TMS)	Sham Transcranial Magnetic Stimulation
Arm/Group Description	A Magstim 200 (Magstim, UK) and 14cm circular coil positioned tangential to the head will be used to deliver stimuli at 100% of maximum stimulator output. Transcranial Magnetic Stimulation will be applied to three regions: 1) 4cm lateral to the right of the inion, 2) centered on the inion, 3) 4cm lateral to the left of the inion. Five pulses separated by 6 seconds will be delivered with a counter-clockwise current, followed by the same five pulses delivered with a clockwise current, for a total of 10 pulses per region, and 30 pulses per session. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.	A sham condition of Transcranial Magnetic Stimulation will be used and follow the same protocol as the active stimulation; however no magnetic pulses will be delivered through the scalp. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.
Measure Participants	10	10
Mean (Standard Deviation) [percentage change]	-21.5 (14.9)	13.2 (29.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transcranial Magnetic Stimulation (TMS), Sham Transcranial Magnetic Stimulation
	Comments
	Type of Statistical Test	Equivalence
	Comments	We hypothesized that the real TMS would improve the standing postural control stability (i.e., greater percent decrease increase of postural sway speed from baseline) as compared to the sham TMS.
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	t-test, 2 sided
	Comments

6. Other Pre-specified Outcome

Title	Percent Change From Baseline to Post Treatment on Mobility and Turning
Description	Mobility and turning is assessed by the timed up-and-go test (Podsiadlo & Richardson, 1991). The participant will be seated in an armed chair. On the word "go," the subject will stand up using the arm rests if needed, walk (with assistive device if needed) around a cone placed three meters in front of the chair, return and sit down as quickly as possible.
Time Frame	Baseline and 1 week post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcranial Magnetic Stimulation (TMS)	Sham Transcranial Magnetic Stimulation
Arm/Group Description	A Magstim 200 (Magstim, UK) and 14cm circular coil positioned tangential to the head will be used to deliver stimuli at 100% of maximum stimulator output. Transcranial Magnetic Stimulation will be applied to three regions: 1) 4cm lateral to the right of the inion, 2) centered on the inion, 3) 4cm lateral to the left of the inion. Five pulses separated by 6 seconds will be delivered with a counter-clockwise current, followed by the same five pulses delivered with a clockwise current, for a total of 10 pulses per region, and 30 pulses per session. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.	A sham condition of Transcranial Magnetic Stimulation will be used and follow the same protocol as the active stimulation; however no magnetic pulses will be delivered through the scalp. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.
Measure Participants	10	10
Mean (Standard Deviation) [percentage change]	-12.8 (11.7)	-9.3 (15.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transcranial Magnetic Stimulation (TMS), Sham Transcranial Magnetic Stimulation
	Comments
	Type of Statistical Test	Equivalence
	Comments	We hypothesized that the real TMS would improve the performance of TUG test (i.e., greater percent decrease of time to complete TUG test from baseline) as compared to the sham TMS.
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	2 months
Arm/Group Title	Transcranial Magnetic Stimulation (TMS)		Sham Transcranial Magnetic Stimulation
Arm/Group Description	A Magstim 200 (Magstim, UK) and 14cm circular coil positioned tangential to the head will be used to deliver stimuli at 100% of maximum stimulator output. Transcranial Magnetic Stimulation will be applied to three regions: 1) 4cm lateral to the right of the inion, 2) centered on the inion, 3) 4cm lateral to the left of the inion. Five pulses separated by 6 seconds will be delivered with a counter-clockwise current, followed by the same five pulses delivered with a clockwise current, for a total of 10 pulses per region, and 30 pulses per session. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.		A sham condition of Transcranial Magnetic Stimulation will be used and follow the same protocol as the active stimulation; however no magnetic pulses will be delivered through the scalp. Transcranial Magnetic Stimulation: 0.2 Hz (5 pulses every six seconds in a counter-clockwise current, followed by the same five pulses in a clockwise current); 10 pulses per region, 30 pulses per session; 5 days a week for 4 weeks.
All Cause Mortality
	Transcranial Magnetic Stimulation (TMS)		Sham Transcranial Magnetic Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Transcranial Magnetic Stimulation (TMS)		Sham Transcranial Magnetic Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Transcranial Magnetic Stimulation (TMS)		Sham Transcranial Magnetic Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.