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

• ClinicalTrials.gov Identifier: NCT02528071
• Recruitment Status: Terminated
• First Posted: August 19, 2015
• Last Update Posted: January 5, 2021
• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Information provided by (Responsible Party): Centre Hospitalier Universitaire de Saint Etienne

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment
ALS (Amyotrophic Lateral Sclerosis)	Other: Diaphragmatic endurance test

Study Design

• Study Type: Observational
• Actual Enrollment: 136 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Prognostic Value of a Diaphragmatic Endurance Test in Patients With Amyotrophic Lateral Sclerosis : Impact and Prognosis. Single-center Prospective Pilot Study
• Actual Study Start Date: September 29, 2014
• Actual Primary Completion Date: October 28, 2020
• Actual Study Completion Date: October 28, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Patients; 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; 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
Control; 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; 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

Outcome Measures

Primary Outcome Measures :

1. Endurance time [ Time Frame: Day 1 ]
   Difference in endurance time during the IHT between healthy controls and ALS patients when diagnosis is established

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Patients with ALS Healthly volonteers

Criteria

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

Contacts and Locations

Locations

France

CHU de SAINT-ETIENNE

Saint-etienne, France, 42000

Sponsors and Collaborators

Centre Hospitalier Universitaire de Saint Etienne

Investigators

• Study Chair: Frederic COSTES, MD PhD; CHU de CLERMONT-FERRAND
• Principal Investigator: Isabelle COURT-FORTUNE, MD; CHU de Saint-Etienne

More Information

• Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
• ClinicalTrials.gov Identifier: NCT02528071
• Other Study ID Numbers: 1308188; 2014-A00309-38 ( Other Identifier: ANSM )
• First Posted: August 19, 2015
• Last Update Posted: January 5, 2021
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:

Amyotrophic Lateral Sclerosis; ALS; Diaphragmatic Endurance Test

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases