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| ID | Type | Description | Link |
|---|---|---|---|
| 1R21NS085491-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Transcranial Magnetic Stimulation (TMS) | Active Comparator | 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. |
|
| Sham Transcranial Magnetic Stimulation | Sham Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation | Device | 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 | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline to Post Treatment on the Scale for the Assessment and Rating of Ataxia (SARA) | 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. | Baseline and 1 week post treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline to Post Treatment on the Timed 25-Foot Walk | 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. | Baseline and 1 week post treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline to Post Treatment on Gait Speed in 90 Second Walking Test | 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. |
Inclusion Criteria:
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:
History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG.
TMS and MRI-Specific exclusion criteria including:
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| Name | Affiliation | Role |
|---|---|---|
| Alvaro Pascual-Leone, MD, PhD | Beth Israel Deaconess Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30809184 | Derived | Manor B, Greenstein PE, Davila-Perez P, Wakefield S, Zhou J, Pascual-Leone A. Repetitive Transcranial Magnetic Stimulation in Spinocerebellar Ataxia: A Pilot Randomized Controlled Trial. Front Neurol. 2019 Feb 12;10:73. doi: 10.3389/fneur.2019.00073. eCollection 2019. |
| Label | URL |
|---|---|
| Information on TMS and the lab conducting the study | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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. |
| FG001 | 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. 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline to Post Treatment on the Scale for the Assessment and Rating of Ataxia (SARA) | 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. | Posted | Mean | Standard Deviation | percentage change | Baseline and 1 week post treatment |
|
2 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Brad Manor, Ph.D. | Beth Israel Deaconess Medical Center | 617-971-5332 | bmanor@bidmc.harvard.edu |
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| ID | Term |
|---|---|
| D020754 | Spinocerebellar Ataxias |
| D001259 | Ataxia |
| ID | Term |
|---|---|
| D002524 | Cerebellar Ataxia |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
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|
| Percent Change From Baseline to Post Treatment on the 9-hole Peg Test |
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. |
| Baseline and 1 week post treatment |
| Baseline and 1 week post treatment |
| Percent Change From Baseline to Post Treatment on Standing Postural Control | 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). | Baseline and 1 week post treatment |
| Percent Change From Baseline to Post Treatment on Mobility and Turning | 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. | Baseline and 1 week post treatment |
| Information on Ataxia | View source |
| BG001 | 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. 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. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 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. 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. |
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|
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| Secondary | Percent Change From Baseline to Post Treatment on the Timed 25-Foot Walk | 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. | Posted | Mean | Standard Deviation | percentage change of maximum gait speed | Baseline and 1 week post treatment |
|
|
|
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| Secondary | Percent Change From Baseline to Post Treatment on the 9-hole Peg Test | 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. | Posted | Mean | Standard Deviation | percentage change | Baseline and 1 week post treatment |
|
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| Other Pre-specified | Percent Change From Baseline to Post Treatment on Gait Speed in 90 Second Walking Test | 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. | Posted | Mean | Standard Deviation | percentage change | Baseline and 1 week post treatment |
|
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|
|
| Other Pre-specified | Percent Change From Baseline to Post Treatment on Standing Postural Control | 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). | Posted | Mean | Standard Deviation | percentage change | Baseline and 1 week post treatment |
|
|
|
|
| Other Pre-specified | Percent Change From Baseline to Post Treatment on Mobility and Turning | 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. | Posted | Mean | Standard Deviation | percentage change | Baseline and 1 week post treatment |
|
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|
|
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | 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. 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. | 0 | 10 | 0 | 10 |
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| D009422 |
| Nervous System Diseases |
| D013132 | Spinocerebellar Degenerations |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |