Non-invasive Brain Stimulation and Exercise Intervention for Patients With Motor Neuron Disease

NCT07067229 | Recruiting DMC

• 1 other identifier: COA No. 1142/2024
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Motor neuron disease (MND) is a progressive neurological disorder involving degeneration of motor neurons, leading to muscle weakness, speech and swallowing difficulties, and respiratory failure. This study aims to develop a novel treatment approach combining personalized repetitive transcranial magnetic stimulation (rTMS) with mixed reality (MR) exercise-based games (exergames) to slow disease progression and improve quality of life. In this randomised controlled trial study will compare three groups: (1) rTMS with MR exercise (personalized intervention), (2) rTMS with MR exercise (standard intervention), and (3) sham rTMS with MR exercise. Outcomes will be assessed at baseline, 3 months, and 6 months post intervention. The long-term goal is to implement this approach in clinical settings to enhance care for people with MND.

Conditions

ALS (Amyotrophic Lateral Sclerosis)

Keywords

Amyotrophic Lateral Sclerosis; Transcranial Magnetic Stimulation; Intervention; Augmented Reality

Outcome Measures

Primary Outcomes (5)

• Amyotrophic Lateral Sclerosis Functional rating scale - revised version (ALSFRS-R)

  The Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) is a 12-item questionnaire used to assess functional ability in people with ALS across four domains: bulbar, fine motor, gross motor, and respiratory function. Each item is scored from 0 (unable) to 4 (normal), with a total score ranging from 0 to 48. It can be self-reported or clinician-administered in person, by phone, or online. Lower scores indicate greater disability. The ALSFRS-R is used to monitor disease progression and guide clinical care.

  ALSFRS-R will be measured at three time points (baseline, 3-month, and 6-month post intervention).

• Muscle evoke potential (MEP)

  Participants will be stimulated at the primary motor cortex by transcranial magnetic stimulation to measure cortical excitability, which sends the motor outputs to Tibialis Anterior (TA) and Abductor Pollicis Brevis (APB) muscles. The MEP will be used to assess muscle activity in these muscles during the stimulation. The MEP will be measured in mV.

  MEP will be mesured at three time points (baseline, 3-month, and 6-month post intervention).

• Motor unit number estimation (MScan fit-MUNE)

  For MScan fit-MUNE, CMAP is recorded at multiple stimulation intensities. The MScan fit-MUNE software then generates a curve representing the relationship between stimulation intensity and CMAP amplitude. A mathematical model is fitted to this curve to estimate the number of motor units contributing to the generation of the CMAP.

  MScan fit-MUNE will be mesured at three time points (baseline, 3-month, and 6-month post intervention).

• Motor unit number index (MUNIX)

  For MUNIX (Motor Unit Number Index), the procedure begins with recording the CMAP. Then, the participant is asked to gently contract the muscle. During this contraction, the interference pattern of muscle electrical activity is recorded. The MUNIX value is calculated by analyzing the ratio between the CMAP amplitude and the amplitude of the interference pattern. This provides an estimate of motor unit function.

  MUNIX will be measured at three time points (baseline, 3-month, and 6-month post intervention).

• Cortical silent period (CSP)

  Participants will be stimulated at the primary motor cortex by transcranial magnetic stimulation to measure cortical excitability, which sends the motor outputs to Tibialis Anterior (TA) and Abductor Pollicis Brevis (APB) muscles. The CSP will be used to assess muscle activity in these muscles during the stimulation. The CSP will be measured in ms.

  Muscle evoke potential will be measured at three time points (baseline, 3-month, and 6-month post intervention).

Secondary Outcomes (11)

• Muscle mass

  Muscle mass will be measured at three time points (baseline, 3-month, and 6-month post intervention).

• Body mass index (BMI)

  BMI will be measured at three time point (baseline, 3-month, 6-month post intervention).

• Hand grip test

  Hand grip test will be measured at three time points (baseline, 3-month, and 6-month post intervention).

• Pinch grip test

  Pinch grip test will be measured at three time points (baseline, 3-month, and 6-month post intervention).

• Hand function

  Hand function will be measured at three time points (baseline, 3-month, and 6-month post intervention).

Study Arms (3)

Personalized intervention group

EXPERIMENTAL

Participants will receive personalised repetitive transcranial magnetic stimulation mixed reality.

Device: Personalized rTMS

Standard intervention group

ACTIVE COMPARATOR

Participants will receive standard repetitive transcranial magnetic stimulation plus mixed reality.

Device: Standard rTMS

Sham group

SHAM COMPARATOR

Participants will receive sham repetitive transcranial magnetic stimulation mixed reality.

Device: Sham rTMS

Interventions

Personalized rTMS DEVICE

Personalized repetitive transcranial magnetic stimulation (TMS) together with mixed-reality (MR) exercise

Personalized intervention group

Standard rTMS DEVICE

Standard repetitive transcranial magnetic stimulation (TMS) together with mixed-reality (MR) exercise

Standard intervention group

Sham rTMS DEVICE

Sham rTMS together with mixed-reality (MR) exercise

Sham group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants aged between 18 and 80 years
• Diagnosed with any type of motor neuron disease (MND)
• Have mild to moderate severity, as assessed by the Sinaki-Mulder scale, with a severity level between 1 and 3

You may not qualify if:

• History of other neurological disorders, such as stroke
• Use of ventilatory support
• Severe dementia

Sponsors & Collaborators

• Chulalongkorn University: lead
• King Chulalongkorn Memorial Hospital: collaborator

Study Sites (1)

King Chulalongkorn Memorial hospital, The Thai Red Cross Society

Bangkok, Pathumwan, 10330, Thailand

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Jakkrit Amornvit, MD

  Chulalongkorn University

  PRINCIPAL INVESTIGATOR

• Phunsuk Kantha, PT.,PhD

  Mahidol University

  PRINCIPAL INVESTIGATOR

• Kulvara Lapanan, PT

  Chulalongkorn University and Neuroscience Resesarch Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jakkrit Amornvit, MD

CONTACT

Thailand: 88-951-9195; jakkrit.a@chula.ac.th

Phunsuk Kantha, PT.,PhD

CONTACT

Thailand: 93-295-1646; phunsuk.kan@mahidol.ac.th

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2025
• First Posted: July 16, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: September 25, 2025

Record last verified: 2025-07

Locations

TH (1)