Cerebellar rTMS and Physical Therapy for Cerebellar Ataxia

Effect of Repetitive Transcranial Magnetic Stimulation With Intensive Physical Therapy in Cerebellar Ataxia: A Pilot Study

The present study investigated the efficacy and safety of combination treatment of repetitive transcranial magnetic stimulation (rTMS) and physical therapy (PT) in patients with cerebellar variant of multiple system atrophy (MSA-C) and spinocerebellar ataxia.

Study Overview

• Status: Completed
• Conditions: Spinocerebellar Ataxias; Multiple System Atrophy, Cerebellar Variant (Disorder)
• Intervention / Treatment: Device: Cerebellar repetitive transcranial magnetic stimulation

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The patients with probable MSA-C and spinocerebellar ataxia (SCA)
2. cerebellar ataxia as main clinical presenting feature and able to walk independently without walking devices
3. aged over 20
4. presence of cerebellar atrophy proven by brain MRI.

Exclusion Criteria:

1. secondary cerebellar ataxia
2. peripheral neuropathy, radiculopathy, or decreased visual acuity that can cause peripheral ataxia
3. musculoskeletal disease affecting gait or balance
4. other neurologic symptoms, including symptomatic parkinsonism (two or more rigidity and/or bradykinesia scores in one limb by Unified Parkinson's disease Rating Scale part 3) or spasticity (20)
5. psychiatric symptoms requiring medication or with cognitive decline (Mini-mental state examination [MMSE] < 20)
6. taking any sedative medications or anti-parkinsonian medications such as benzodiazepine, levodopa or dopamine agonist
7. history of seizure or metallic brain implants; (8) cardiopulmonary diseases causing dyspnea during exercise.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Cerebellar rTMS + Physical therapy; rTMS was delivered on the scalp for over 2 cm under the inion, which is the scalp over the cerebellum area, using a double-cone coil connected to a Magstim Rapid2® stimulator with two Booster Modules (Magstim, Spring Gardens, Wales, UK) in accordance with safety recommendations. Stimulation was delivered to the cerebellum at 10 Hz with 90% of the mean resting motor threshold intensity for 5 seconds at 55 second intervals to deliver 1000 pulses in 20 minutes. Immediately after rTMS, the combination treatment group received balance and gait training by a physical therapist for 30 minutes/day and underwent aerobic exercise using a stationary bicycle at moderate intensity (12 to 14 rating of perceived exertion) for 30 minutes/day and 5 days/week for two weeks. In the control group, no participants received physical therapy or rTMS for two weeks.	Device: Cerebellar repetitive transcranial magnetic stimulation; rTMS was delivered on the scalp for over 2 cm under the inion, which is the scalp over the cerebellum area, using a double-cone coil connected to a Magstim Rapid2® stimulator with two Booster Modules (Magstim, Spring Gardens, Wales, UK) in accordance with safety recommendations. Stimulation was delivered to the cerebellum at 10 Hz with 90% of the mean resting motor threshold intensity for 5 seconds at 55 second intervals to deliver 1000 pulses in 20 minutes. Immediately after rTMS, the combination treatment group received balance and gait training by a physical therapist for 30 minutes/day and underwent aerobic exercise using a stationary bicycle at moderate intensity (12 to 14 rating of perceived exertion) for 30 minutes/day and 5 days/week for two weeks. In the control group, no participants received physical therapy or rTMS for two weeks.
SHAM_COMPARATOR: Sham stimulation + Physical therapy; Sham stimulation was delivered on the scalp for over 2 cm under the inion, which is the scalp over the cerebellum area, using a double-cone coil connected to a Magstim Rapid2® stimulator. Sham stimulation was delivered to the cerebellum for 5 seconds at 55 second intervals in 20 minutes. Immediately after rTMS, the combination treatment group received balance and gait training by a physical therapist for 30 minutes/day and underwent aerobic exercise using a stationary bicycle at moderate intensity (12 to 14 rating of perceived exertion) for 30 minutes/day and 5 days/week for two weeks. In the control group, no participants received physical therapy or rTMS for two weeks.	Device: Cerebellar repetitive transcranial magnetic stimulation; rTMS was delivered on the scalp for over 2 cm under the inion, which is the scalp over the cerebellum area, using a double-cone coil connected to a Magstim Rapid2® stimulator with two Booster Modules (Magstim, Spring Gardens, Wales, UK) in accordance with safety recommendations. Stimulation was delivered to the cerebellum at 10 Hz with 90% of the mean resting motor threshold intensity for 5 seconds at 55 second intervals to deliver 1000 pulses in 20 minutes. Immediately after rTMS, the combination treatment group received balance and gait training by a physical therapist for 30 minutes/day and underwent aerobic exercise using a stationary bicycle at moderate intensity (12 to 14 rating of perceived exertion) for 30 minutes/day and 5 days/week for two weeks. In the control group, no participants received physical therapy or rTMS for two weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International Cooperative Ataxia Rating Scale (ICARS)	The scale is scored out of 100 with 19 items and 4 subscales of postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders. Higher scores indicate higher levels of impairment.	The change of ICARS score between baseline (T0) and immediately after (T1) treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from temporospatial parameters of gait	Gait parameters measured by GAITRite system	The clinical scales were evaluated by blinded raters at baseline (T0) and immediately after (T1), 4 weeks after (T2), and 12 weeks (T3) after intervention.
Change from posturography	Posturography measured by Pedoscan system	The clinical scales were evaluated by blinded raters at baseline (T0) and immediately after (T1), 4 weeks after (T2), and 12 weeks (T3) after intervention.
Change from Mini-Mental State Examination (MMSE)	Measurement of cognitive function	The clinical scales were evaluated by blinded raters at baseline (T0) and immediately after (T1), 4 weeks after (T2), and 12 weeks (T3) after intervention.
Change from Beck depression inventory (BDI)	Measurement of symptoms of depression	The clinical scales were evaluated by blinded raters at baseline (T0) and immediately after (T1), 4 weeks after (T2), and 12 weeks (T3) after intervention.
Change from Barthel Index for Activities of Daily Living	Measurement of activities of daily living	The clinical scales were evaluated by blinded raters at baseline (T0) and immediately after (T1), 4 weeks after (T2), and 12 weeks (T3) after intervention.
Change from International Cooperative Ataxia Rating Scale (ICARS)	The scale is scored out of 100 with 19 items and 4 subscales of postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders. Higher scores indicate higher levels of impairment.	The clinical scales were evaluated by blinded raters at baseline (T0) and 4 weeks after (T2), and 12 weeks (T3) after intervention.

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Study Director: Jong Hyeon Ahn, Samsung Medical Center, Department of Neurology

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2017
• Primary Completion (ACTUAL): March 31, 2018
• Study Completion (ACTUAL): March 31, 2018

Study Registration Dates

• First Submitted: October 7, 2020
• First Submitted That Met QC Criteria: October 14, 2020
• First Posted (ACTUAL): October 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 20, 2020
• Last Update Submitted That Met QC Criteria: October 14, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Cerebellar Diseases; Ataxia; Multiple System Atrophy; Shy-Drager Syndrome; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations
• Other Study ID Numbers: 2017-10-166

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No