Prognostic Value of a Diaphragmatic Endurance Test in Patients With Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease which involves respiratory muscles and can lead at short term to respiratory failure. The occurrence of respiratory failure is associated with morbidity and an increased mortality. To date, respiratory muscle weakness is predicted from the reduction of vital capacity, maximal inspiratory force, nocturnal symptoms and hypercapnia. Even taken together, the predictive value of these indices is low. The investigators hypothesize that an endurance test of diaphragmatic work would be more sensitive to respiratory muscle involvement than maximal respiratory force. Consequently, the investigators assessed diaphragmatic performance through an isocapnic hyperventilation test (IHT) in patients at the onset of ALS and, then regularly up to the occurrence of respiratory failure. The investigators make the hypothesis that IHT will be altered earlier than maximal inspiratory force

Official Title
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Prognostic Value of a Diaphragmatic Endurance Test in Patients With Amyotrophic Lateral Sclerosis : Impact and Prognosis. Single-center Prospective Pilot Study

Conditions
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ALS (Amyotrophic Lateral Sclerosis)

Intervention / Treatment
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* Other: Diaphragmatic endurance test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Patients : Older than 18 years old and younger than 80 years old ALS patient seen during the diagnostic assessment Inclusion Criteria for control group : Older than 25 years old and younger than 80 years old No respiratory or neurologic active pathology Exclusion Criteria for Patients : Bulbar ALS (inability to perform maximal respiratory maneuvers) Dementia Respiratory failure at diagnosis (arterial carbon dioxide partial pressure (pCO2) > 45 mmHg) Respiratory or neurologic active pathology Exclusion Criteria for control group : Chest wall deformation with spirometric defect

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients<br>ALS patients performing measurements of maximal respiratory forces, diaphragmatic endurance during a diaphragmatic endurance test and phrenic nerve activity at the onset of the disease and repeated every 3 months up to respiratory failure or death | Other: Diaphragmatic endurance test<br>* This consists of hyperventilation in a flask while maintaining the constant level of Carbon Dioxide (CO2). The patient will realize hyperventilation to increasing levels of Maximum Minute Ventilation (MMV), corresponding to increasing levels of respiratory rate, until exhaustion<br>|
| Control<br>Healthy controls performing measurements of maximal respiratory forces, diaphragmatic endurance during a diaphragmatic endurance test and phrenic nerve activity. This arm will enable to establish reference values of IHT | Other: Diaphragmatic endurance test<br>* This consists of hyperventilation in a flask while maintaining the constant level of Carbon Dioxide (CO2). The patient will realize hyperventilation to increasing levels of Maximum Minute Ventilation (MMV), corresponding to increasing levels of respiratory rate, until exhaustion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endurance time | Difference in endurance time during the IHT between healthy controls and ALS patients when diagnosis is established | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reference values of the diaphragmatic endurance test | Reference values of the diaphragmatic endurance test in healthy controls according to age, by 10 years range. | Day 1 | 
| Reference values of phrenic nerve activity | Reference values of phrenic nerve activity in healthy controls according to age. It is measured with diaphragmatic Electromyogram by cervical electrical stimulation. | Day 1 | 
| Slope of endurance time decrease | Slope of endurance time decrease with time in ALS patients measured during IHT | At Day 1 and every 3 months of follow-up (3 years) | 
| Amplitude of phrenic nerve | It is the relationship between phrenic nerve activity and diaphragmatic endurance in ALS patients | At Day 1 and every 3 months of follow-up (3 years) | 
| Latency of phrenic nerve | It is the relationship between phrenic nerve activity and diaphragmatic endurance in ALS patients | At Day 1 and every 3 months of follow-up (3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis, ALS, Diaphragmatic Endurance Test