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Transcranial Magnetic Stimulation in Spino-Cerebellar Ataxia (TMS)

Primary Purpose

Spinocerebellar Ataxia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Transcranial Magnetic Stimulation
Sponsored by
Beth Israel Deaconess Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinocerebellar Ataxia focused on measuring Spinocerebellar Ataxia, SCA, Ataxia, Transcranial Magnetic Stimulation, TMS

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Transcranial Magnetic Stimulation (TMS)

Sham Transcranial Magnetic Stimulation

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
September 24, 2013
Last Updated
April 19, 2017
Sponsor
Beth Israel Deaconess Medical Center
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT01975909
Brief Title
Transcranial Magnetic Stimulation in Spino-Cerebellar Ataxia
Acronym
TMS
Official Title
Transcranial Magnetic Stimulation (TMS) in Spino-Cerebellar Ataxia
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinocerebellar Ataxia
Keywords
Spinocerebellar Ataxia, SCA, Ataxia, Transcranial Magnetic Stimulation, TMS

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Transcranial Magnetic Stimulation (TMS)
Arm Type
Active Comparator
Arm 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.
Arm Title
Sham Transcranial Magnetic Stimulation
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Transcranial Magnetic Stimulation
Other Intervention Name(s)
Magstim 200
Intervention Description
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.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
Other Pre-specified Outcome Measures:
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: The patient's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other CNS active drugs. 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: Known metal in the head (such as a surgical aneurysm clip) or a history of prior neurosurgical procedures. 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. Subjects who have or might have bullet fragments or other shrapnel (veterans or workers exposed to metal in their work environment). Subjects with metallic paint (e.g. color contact lenses, tattoos, metallic eyeliner) Subjects expressing significant claustrophobia.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alvaro Pascual-Leone, MD, PhD
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30809184
Citation
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.
Results Reference
derived
Links:
URL
http://tmslab.org/
Description
Information on TMS and the lab conducting the study
URL
http://www.ataxia.org/
Description
Information on Ataxia

Learn more about this trial

Transcranial Magnetic Stimulation in Spino-Cerebellar Ataxia

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