Individualized Functional Imaging-Guided Repetitive Transcranial Magnetic Stimulation (rTMS) for Treating Postural Gait Disorders in Patients with Amyotrophic Lateral Sclerosis (ALS): a Randomized, Crossover, Controlled, Double-Blind Clinical Study (iFIRST-ALS)

Peking University

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Amyotrophic Lateral Sclerosis (ALS)

Treatments: Device: Transcranial Magnetic Stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT06819358

M2024877

Details and patient eligibility

About

This study is a randomized, crossover, controlled, double-blind clinical trial. Patients (n=45) were randomly divided into Group A and Group B. Patients in Group A will receive 2 weeks (10800 Hz daily, 5 days×2) of Transcranial magnetic stimulation（TMS） treatment, while patients in Group B will receive sham stimulation with the same frequency. After a 4-week washout period, the two groups cross over. Patients in Group A will receive sham stimulation, and patients in Group B will receive TMS treatment for 2 weeks (10800 Hz daily, 5 days×2). Clinical functional scales, imaging evaluations, and gait analysis will be conducted at baseline, after 2 weeks of treatment, before crossover treatment, and after 2 weeks of crossover treatment. The therapist, patients, and assessors will be all blinded throughout the study.

Enrollment: 45 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged 18-80 years;
2. Diagnosis of motor neuron disease at probable level or above based on Estorial criteria;12
3. Meet UMND ALS diagnosis criteria: at least three segments of upper motor neuron damage localized to 1-2 muscles, or EMG indicating loss of innervation in 1-2 muscles;13
4. Presence of lower limb dysfunction: Berg balance scale score below 40;
5. Capable of standing independently for more than 30 seconds and able to walk or walk with assistance;
6. Stable medication dosage for at least one month;
7. FVC > 60%;
8. Signed informed consent.

Exclusion criteria

1. History of substance abuse within the past 6 months;
2. History of epilepsy or first-degree relative with epilepsy;
3. Patients with severe systemic diseases in the heart, lungs, liver, or kidneys that cannot be controlled with routine medications, based on laboratory results;
4. Patients with severe depression or anxiety (HAMD-17 score ≥18; HAMA score ≥21) or diagnosed with other mental illnesses;
5. Patients with a life expectancy of less than one year due to reasons other than neurodegenerative diseases;
6. Pregnant women or those planning to become pregnant;
7. Individuals with a pacemaker, cochlear implant, or other metallic foreign bodies and any implanted electronic equipment, or those with contraindications for MRI scanning or TMS treatment, such as claustrophobia;
8. Patients who have received TMS, transcranial electrical stimulation, transcranial focused ultrasound, or other neuromodulation treatments within three months prior to enrollment;
9. Other abnormal examination results deemed unsuitable for participation by the research investigator;
10. Inability to cooperate for follow-ups due to geographical or other reasons;
11. Participation in other clinical research trials.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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45 participants in 2 patient groups

Group A

Active Comparator group

Treatment:

Device: Transcranial Magnetic Stimulation

Group B

Sham Comparator group

Treatment:

Device: Transcranial Magnetic Stimulation