rTMS for Cerebellar Ataxia in Children

NCT07211490 | Not Yet Recruiting

• 1 other identifier: rTMSCAHKU
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Dysfunction of the cerebellum can result in cerebellar ataxia (CA), typically marked by symptoms such as movement incoordination, gait instability, articulation disorder, oculomotor and swallowing difficulties. Children affected by paediatric cerebellar ataxia (PCA) often suffer from an array of motor symptoms, affecting their quality of life and psychosocial well-being. It was estimated that PCA affects 26/100,000 children worldwide for both genetic and acquired causes. Epidemiological data on PCA, however, are absent in the Hong Kong population. PCAs comprise a varied group of cerebellar development disorders, marked by impaired balance and motor coordination (e.g., dysmetria and tremor) when performing voluntary movement. Clinical symptoms in children with PCA are related to lesioned localization - focal disorder of the cerebellar vermis leads to truncal instability, head titubation, and nystagmus; while lesioned cerebellar hemispheres results in ataxia gait (wide-staggering gait, tend to fall towards the affected side). These clinical symptoms result in functional difficulties involving balance and walking, reaching, grasping and manipulation, oculomotor and speech domains. Abnormalities of motor excitability have been reported in patients with cerebellar lesions - the motor threshold was found to be raised in the motor cortex contralateral to a hemi-cerebellar lesion. With no effective pharmacological treatments available, rehabilitation serves as the primary treatment approach. Even though adaptive learning is affected by cerebellar lesion, motor learning is still possible via exercise interventions. Interventions may include compensatory (educate strategies to compensate for impairment) or restorative approaches (improve functions through training). While exercise interventions have been explored as a potential therapeutic approach for paediatric patients with cerebellar lesions or degeneration, the current evidence lacks robust, high-quality randomized controlled trials (RCTs) to substantiate their efficacy. Existing evidence shows that cerebellar outputs project to several cortical areas, including the primary motor cortex (M1). CA patients with lesions in structures of the cerebellar efferent pathway exhibit reduced inhibition in the motor cortex. Selective modulation of the efferent pathways may offer an additional means of modulating cortical activity, thus improve motor coordination abilities in CA patients. With the development of non-invasive brain stimulation (NIBS) techniques, more research has been conducted using NIBS as treatment modalities for patients with CA. The most used NIBS techniques include repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). Repetitive transcranial magnetic stimulation (rTMS) enables to modulate cortical excitability focally in conscious subjects; low-frequency stimulation (e.g., 1 Hz) is known to suppress cortical excitability, while higher frequencies (\> 5 Hz) induce facilitation. These changes in excitability occur not only at the site of stimulation but also at other distant interconnected sites of a network. Both the excitatory stimulation and inhibitory stimulation approaches were adopted in existing adult studies. Paediatric patients with cerebellar lesions-caused by stroke, tumour, or genetic conditions-are thought to share the same pathophysiological basis as adults. Using contra-lesional inhibitory rTMS, França et al. demonstrated that the intervention is safe and feasible for adult patients with CA, showing a reduction in ataxic symptoms. Despite promising results in the adult population, it is still unclear whether rTMS can relieve ataxic symptoms and improve motor performance in children with CA. To date, no studies have been published on the effects of rTMS on improving ataxic symptoms in children with cerebellar ataxia. However, emerging evidence suggests its potential utility. Using rTMS of 1 Hz to stimulate the cerebellar hemisphere ipsilateral to the ataxic side combined with mirror therapy, Cha et al. demonstrated that there was improvement in functional mobility as measured by 6-minute walk test and the timed up and go test. Supporting the feasibility of rTMS in paediatric motor rehabilitation, our pilot RCT (HKWC UW 23-492) found that contra-lesional inhibitory rTMS over M1 combined with motor training is safe and effective in improving motor performance in children with cerebral palsy. Comparative studies in older adults suggest that cerebellar rTMS was more effective than M1 rTMS for motor learning and the consolidation, likely due to the unique role of cerebellum in the integration and processing of multimodal sensory inputs to refine motor planning. These findings highlight the cerebellum as a promising neuromodulatory target for motor rehabilitation, warranting further investigation in paediatric cerebellar ataxia.

Conditions

Cerebellar Ataxia

Keywords

TMS; Cerebellar ataxia; Children

Outcome Measures

Primary Outcomes (2)

• The Scale for Assessment and Rating of Ataxia (SARA)

  an evaluation tool for cerebellar ataxia patients. It consists of the following items: gait, stance, sitting, speech disturbance, finger chase, finger-nose test, fast alternating hand movements, and heel-shin slide.

  Day 10, 17 of intervention and 2 months post intervention.

• The International Cooperative Ataxia Rating Scale (ICARS)

  an assessment scale for severity of cerebellar ataxia. ICARS consists of 19 items divided into four sub-scores: posture and gait disturbances, (limb) kinetic functions, speech disorders, and oculomotor disorders.

  Day 10, 17 of intervention and 2 months post intervention.

Secondary Outcomes (4)

• The 10 Metre Walk Test (10MWT)

  Day 10, 17 of intervention and 2 months post intervention.

• The Timed Up and Go Test (TUG)

  Day 10, 17 of intervention and 2 months post intervention.

• Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2), Subtests 4 and 7

  Day 10, 17 of intervention and 2 months post intervention.

• The Pediatric Balance Scale (PBS)

  Day 10, 17 of intervention and 2 months post intervention.

Study Arms (2)

Interventional rTMS group

EXPERIMENTAL

The intervention group will receive 1 Hz rTMS for 15 minutes, followed by 1.5 hours of motor training.

Device: Repetitive Transcranial Magnetic Stimulation

Sham rTMS group

SHAM COMPARATOR

The sham group will not receive any Hz of rTMS for 20 minutes, followed by 1.5 hours of motor training.

Device: Sham Repetitive Transcranial Magnetic Stimulation

Interventions

Repetitive Transcranial Magnetic Stimulation DEVICE

1 Hz rTMS for 20 minutes, followed by 1.5 hours of motor training.

Interventional rTMS group

Sham Repetitive Transcranial Magnetic Stimulation DEVICE

Sham Hz rTMS for 20 minutes, followed by 1.5 hours of motor training.

Sham rTMS group

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients aged ≥ 4 years old - 18 years old fulfilling the following criteria: 1) diagnosis of cerebellar ataxia based on clinical history and neurological examination; 2) cerebellar lesion seen by MRI; 3) IQ ≥ 50 to ensure sufficient cognitive capacity for comprehending and adhering to motor training protocols.

You may not qualify if:

• Patients will be excluded if they have: 1) Sensory ataxia with etiologies involving the peripheral nerves or posterior columns of the spinal cord, 2) Any contra-indications to rTMS, 3) Severe spasticity (defined as a score of 4 in the Modified Ashworth Scale) and contractures, 4) Uncontrollable epilepsy defined as the occurrence of seizures despite the use of at least one anti-epileptic drug (AED) in adequate dose, 5) History of Botulinum toxin A injection or upper limb casting in previous 6 months, and 6) Cerebellar ataxia resulting from genetic conditions.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

The University of Hong Kong

Hong Kong, Hong Kong, China

Location

MeSH Terms

Conditions

Cerebellar Ataxia

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

Wan Yee Winnie Tso Professor, MBBS

CONTACT

+85222554295; wytso@hku.hk

Chai Yin Charlie Fan Miss, OT, BSc

CONTACT

+85222554375; charliefan@connect.hku.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: October 8, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: October 8, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)