Contribution of Diaphragmatic Ultrasound for Monitoring Diaphragmatic Function in Patients With Amyotrophic Lateral Sclerosis (ALSUS)

Amyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease that occurs in adults. It is characterized by a progressive degeneration of the first and second motor neurons leading to muscle failure. In its spinal form, ALS manifests by a progressive worsening of limb involvement, whereas the bulbar form presents with swallowing disorders, dysarthria and feeding difficulties.

Respiratory impairment is the most serious feature of ALS. Phrenic nerve damage causes diaphragmatic weakness, which inevitably leads to chronic restrictive respiratory failure. At the stage of symptomatic nocturnal or diurnal alveolar hypoventilation, non-invasive ventilation (NIV) prolongs survival while improving quality of life by relieving respiratory symptoms.

The indication for the initiation of NIV is based on the appearance of respiratory symptoms but also on the demonstration of diaphragmatic insufficiency. A quarterly follow-up of diaphragmatic function has been recommended by the French Health Authority since 2006. It is based on functional respiratory explorations (VC in sitting and lying position, measurement of maximal inspiratory pressure) and screening for diurnal or nocturnal hypoventilation with the measurement of PaCO2 or the nocturnal recording of SpO2.

Access to these examinations remains limited and they are sometimes complex to perform (in particular issues with mouth occlusion during respiratory manoeuvres in case of bulbar damage). Thus, only 60% of patients undergo a complete evaluation. Moreover, these explorations are only late markers of diaphragmatic dysfunction, and it has recently been shown that they do not correlate with histological diaphragmatic amyotrophy.

The development of new, reliable, and easily available tools for the evaluation of diaphragmatic function, and that are capable of detecting diaphragmatic insufficiency early in the course of the disease, are therefore necessary. Such tools would make it easier to implement NIV at the optimal time, preventing episodes of acute respiratory distress.

Recently, diaphragmatic ultrasound has appeared in the ICU as a new tool for assessing diaphragmatic function. It has the advantage of being highly available, inexpensive, non-irradiating, quick to perform, reproducible and very sensitive and specific for the diagnosis of diaphragmatic dysfunction.

In ALS, few studies have investigated the contribution of ultrasound for the diagnosis or follow-up of diaphragmatic dysfunction. In addition, no study so far has compared diaphragmatic ultrasound to complete pulmonary function test (PFT) data or to direct measurement of diaphragmatic pressure (Pdi). Very few publications report the how the diaphragm changes on ultrasound imaging during the disease. Moreover, these studies do not analyse the interest of diaphragmatic ultrasound in the prediction of progression towards respiratory failure with respiratory support, or death. Finally, these studies use different ultrasound measurements of the diaphragm (stroke, thickness, thickening fraction, and thickening fraction ratio, among others) rather than a simple, consensual parameter.

The aim of this study is to describe the evolution of diaphragmatic ultrasound parameters, to identify the parameter that best correlates with other respiratory measures (PFT, PaCO2, nocturnal oximetry) and to determine the prognostic value of diaphragmatic ultrasound in predicting the initiation of NIV or death at 6 and 12 months.

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Procedure: Diaphragmatic ultrasound; Other: Electro-physiological exploration of the diaphragm

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Marjolaine GEORGES; Phone Number: 03.80.29.37.72; Email: marjolaine.georges@chu-dijon.fr

Study Locations

• France
  • Dijon, France, 21000
    • Recruiting
    • Chu Dijon Bourogne
    • Contact: Marjolaine GEORGES; Phone Number: 03.80.29.37.72; Email: marjolaine.georges@chu-dijon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with Amyotrophic Lateral Sclerosis with no indication for non-invasive ventilation

Description

Inclusion Criteria:

• Patient with Amyotrophic Lateral Sclerosis

  • Certain or probable according to the revised Escorial criteria
  • no indication for non-invasive ventilation
• Adult patient
• Patient who has given oral consent
• Patient who speaks and reads French

Exclusion Criteria:

• Patients with pre-existing diaphragmatic dysfunction requiring non-invasive ventilation
• Person who is not affiliated to national health insurance
• Person subject to a legal protection measure (curatorship, guardianship)
• Patients deprived of their liberty
• Pregnant, parturient or breastfeeding women

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Amyotrophic Lateral Sclerosis; ALS; certain or probable according to the revised Escorial criteria; no indication for non-invasive ventilation	Procedure: Diaphragmatic ultrasound; duration 15 minutes, performed at M0, M3, M6 and M9; Other: Electro-physiological exploration of the diaphragm; duration between 30 and 60 minutes performed at M0

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ultrasound measurement of the diaphragmatic stroke	Up to Month 9
Ultrasound measurement of diaphragmatic thickness	Up to Month 9

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2023
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: April 25, 2022
• First Submitted That Met QC Criteria: April 25, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 13, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: GEORGES 2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No