Transcranial Magnetic Stimulation in Spino-Cerebellar Ataxia

Transcranial Magnetic Stimulation (TMS) in Spino-Cerebellar Ataxia

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01975909

Acronym

TMS

Enrollment

Registered

2013-11-05

Start date

2013-09-30

Completion date

2016-11-30

Last updated

2017-05-30

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

Conditions

Spinocerebellar Ataxia

Keywords

Spinocerebellar Ataxia, SCA, Ataxia, Transcranial Magnetic Stimulation, TMS

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.

Interventions

DEVICETranscranial 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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

Measure	Time frame	Description
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.
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).
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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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.	10
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.	10
Total	20

Baseline characteristics

Characteristic	Transcranial Magnetic Stimulation (TMS)	Sham Transcranial Magnetic Stimulation	Total
Age, Continuous	52.3 years STANDARD_DEVIATION 10.1	48.6 years STANDARD_DEVIATION 4.8	50.6 years STANDARD_DEVIATION 7.5
Region of Enrollment United States	10 participants	10 participants	20 participants
Sex: Female, Male Female	8 Participants	8 Participants	16 Participants
Sex: Female, Male Male	2 Participants	2 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 10	0 / 10
serious Total, serious adverse events	0 / 10	0 / 10

Outcome results

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.