The goal of this clinical trial is to determine whether lung insufflation capacity (LIC) training can help maintain respiratory function and prolong tracheostomy-free survival in people with amyotrophic lateral sclerosis (ALS).
The main questions are:
Does early and continuous LIC training slow the decline in forced vital capacity (FVC)? Does LIC training prolong the time to tracheostomy or death?
This single-center study at the National Center of Neurology and Psychiatry (NCNP) in Japan will enroll 25 adults with ALS diagnosed according to the El Escorial or Awaji criteria. This is a single-arm study with no concurrently enrolled control group. Comparative analyses will use matched external controls. PRO-ACT will be used primarily to evaluate short-term respiratory-function trajectories, while JACALS, if data access is approved, will be used primarily to evaluate long-term time-to-event outcomes.
Participants will:
* Use the LIC Trainer device to perform lung insufflation training twice daily at home * Visit the clinic every 3 months for respiratory and functional assessments * Undergo respiratory tests, including FVC, LIC, maximum insufflation capacity (MIC), and cough peak flow (CPF) * Complete the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Age 20 years or older
Diagnosis of amyotrophic lateral sclerosis (ALS) according to the El Escorial or Awaji criteria
Not using noninvasive ventilation (NIV) and without tracheostomy at the start of LIC training
Able to perform study assessments and provide written informed consent (or assisted signature with communication aid)
Chronic pulmonary disease other than ALS (e.g., COPD, interstitial lung disease)
Severe cognitive or communication impairment preventing study participation
Uncontrolled cardiovascular disease, including unstable angina, recent myocardial infarction, decompensated heart failure, serious arrhythmia, severe aortic stenosis, or active myocarditis/endocarditis
Uncontrolled hypertension
Single group
LIC Trainer (Lung Insufflation Capacity Trainer)
DeviceThe LIC Trainer is a medical device designed to enable lung insufflation through a one-way valve system, allowing passive air stacking without voluntary glottic closure. The device includes a safety valve that automatically releases pressure above 60 cmH₂O and a manual relief valve to ensure patient safety. It is used with a bag-valve-mask to deliver multiple assisted insufflations, approximately 10 per session, twice daily. Participants with amyotrophic lateral sclerosis (ALS) perform LIC training at home after initial instruction by physical therapists and are re-evaluated every 3 months for up to 36 months.
Overall survival (time to tracheostomy or death)
Overall survival is defined as the time from the initiation of lung insufflation capacity (LIC) training to tracheostomy or death, whichever occurs first. Participants who remain alive without tracheostomy at the end of follow-up will be censored at their last known assessment. Survival analysis will use Kaplan-Meier estimates and Cox proportional hazards models. The outcome will also be compared with matched historical controls from the PRO-ACT ALS database using propensity score matching.
Change in forced vital capacity (%FVC)
Forced vital capacity (FVC, expressed as percent predicted) will be measured every 3 months to assess longitudinal respiratory function. The rate of decline in %FVC before and after initiation of LIC training will be compared using linear mixed-effects models.
Change in lung insufflation capacity (LIC) and maximum insufflation capacity (MIC)
LIC and MIC will be assessed at each visit using the LIC Trainer and bag-valve-mask method, respectively. The difference between LIC or MIC and FVC (LIC-FVC, MIC-FVC) will also be evaluated to determine lung and chest wall compliance over time.
Change in cough peak flow (CPF) and assisted CPF
Peak cough flow (CPF) and assisted CPF will be measured using a spirometer to evaluate expiratory muscle strength and effectiveness of airway clearance. Longitudinal changes will be analyzed using mixed-effects models.
Change in ALS Functional Rating Scale-Revised (ALSFRS-R) score
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total and subscale scores (bulbar, limb, and respiratory domains) will be assessed to evaluate overall disease progression. The ALSFRS-R is a 12-item scale with total scores ranging from 0 to 48, where higher scores indicate better functional status and lower scores indicate more severe disability. The monthly slope of ALSFRS-R decline will be calculated and compared with matched historical controls.
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