A Clinical Trial of Early Ventilation in Amyotrophic Lateral Sclerosis (EVENT ALS)

NCT07071935 | Not Yet Recruiting Phase 2 DMC FDA Device

• 2 other identifiers: 858612HT9425-25-1-0154
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

Amyotrophic lateral sclerosis (ALS) is a disease that causes weakness of the muscles of the body. The disease can eventually lead to severe breathing problems, which is the most common cause of death from ALS. The treatment for breathing is non-invasive ventilation (NIV). It is a machine that helps a person breathe by pushing air in and out of their lungs through a mask worn over the face. Research has shown that NIV can improve the quality of life and survival of someone with ALS. Unfortunately, NIV is not equally beneficial for everyone. The investigators do not yet know the best time or method for starting NIV in ALS. Europe and Canada allow starting NIV much earlier in ALS than the United States. Current recommendations for starting NIV are based on the opinion of experts rather than large research studies. Medical insurance companies will not cover NIV until significant breathing weakness occurs. After NIV is started, there is no evidence-based guidance on the best way to adjust NIV to benefit patients as much as possible. Some patients have difficulty tolerating NIV, but it is not clear how to identify these individuals ahead of time. The investigators have created a new prediction tool that can identify patients at high risk of breathing problems within the next 6 months. This may help the study team identify who is more likely to benefit from starting NIV early. The investigators have published a paper that shows that NIV helps people with ALS live longer. This paper also showed that patients get more benefit with use NIV for at least 4 hours per day. The investigators published another paper that measured a gas called carbon dioxide (CO2), which goes high if someone's breathing is weakened. This paper showed that patients with ALS may live longer when CO2 levels are lowered using NIV. The investigators also have data suggesting that certain characteristics may predict who is less likely to use NIV at least 4 hours per day. In this study, the investigators will collect pilot data on starting early NIV in individuals with ALS who do not yet meet insurance criteria for covering NIV. The research team will first use their previously published prediction tool to identify patient risk. Then, subjects would be randomized to start early NIV or to usual care. The usual care group would eventually start NIV as would occur if the participants were not in the study. The purpose of this study is to collect data to help the investigators plan a larger randomized clinical trial. This study has 4 objectives. First, the project aims to identify individuals who would benefit from earlier NIV. The research team will use the original prediction tool to identify risk of severe breathing problems within the next 6 months. Second, the project aims to show that it is feasible to start NIV early. Third, the project aims to gather data on the effect of randomization on symptoms, CO2 levels, and outcomes. Fourth, the project aims to identify traits that may make someone less likely to use NIV.

Conditions

Amyotrophic Lateral Sclerosis (ALS); Respiratory Insufficiency; Positive Pressure Ventilation; Non-invasive Ventilation; Non-invasive Ventilation Support; Non-invasive Ventilatory Support; Chronic Respiratory Failure; Neuromuscular Disease Patients; Neuromuscular Disease; Respiratory Insufficiency Requiring Mechanical Ventilation

Keywords

chronic respiratory failure; chronic neuromuscular respiratory failure; non-invasive ventilation; amyotrophic lateral sclerosis

Outcome Measures

Primary Outcomes (1)

• Time to first use of non-invasive ventilation

  Number of days between randomization to first recorded overnight usage of non-invasive ventilation according to ventilation device data download.

  From enrollment to end of follow-up at approximately 1 year

Secondary Outcomes (13)

• Quality of life questionnaire

  From enrollment to completion of follow-up at approximately 1 year

• Transcutaneous carbon dioxide

  From enrollment to end of follow-up at approximately 1 year

• Oxygen saturation using pulse oximetry

  From enrollment to completion of follow-up at approximately 1 year

• Epworth Sleepiness Scale - Alternative (ESS-ALT) questionnaire

  From enrollment to completion of follow-up at approximately 1 year.

• ALS Functional Rating Scale - Revised (ALSFRS-R) scores

  From enrollment to completion of follow-up at approximately 1 year.

Study Arms (2)

Early Non-invasive Ventilation

EXPERIMENTAL

Participants randomized to this arm will be assigned to start therapy with non-invasive ventilation.

Device: Non-invasive ventilation

Usual care

NO INTERVENTION

Participants randomized to this arm will receive usual care for amyotrophic lateral sclerosis.

Interventions

Non-invasive ventilation DEVICE

Non-invasive ventilation will be started earlier than usual respiratory care guidelines for ALS in the United States.

Also known as: non-invasive positive pressure ventilation, bilevel positive airway pressure

Early Non-invasive Ventilation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with ALS using the Gold Coast Criteria within the last 6 months
• Age ≥18 years
• Willingness and ability to participate in study procedures
• Provision of signed and dated informed consent form

You may not qualify if:

• Current or prior or recommended/prescribed use of NIV including:
• i) bi-level positive pressure ventilation, such as a respiratory assist device or home ventilator ii) Current or prior use of continuous positive airway pressure, or "CPAP" therapy
• Forced vital capacity \<50% of predicted normal
• Maximal inspiratory pressure \> -60 cmH2O (eg, -50 or -40 cmH2O would be excluded)
• Chronic use of supplemental oxygen at any part of the day
• Enrollment in hospice
• Current tracheostomy
• Prior history of sleep apnea where non-invasive ventilation was used or recommended
• Thoracic, abdominal, facial or ophthalmic surgery in the prior 6 weeks
• Coughing up blood
• Myocardial infarction in the previous 4 weeks
• Absolute contraindication to NIV, which includes lethargy, obtundation, facial fractures, active pneumothorax, and airway obstruction (such as a tumor)
• Presence of cognitive dysfunction that would impair ability to complete study procedures, as determined by neurology attending physician

Sponsors & Collaborators

• University of Pennsylvania: lead
• United States Department of Defense: collaborator

Study Sites (3)

Penn State Hershey ALS Clinic

Hershey, Pennsylvania, 17033, United States

Location

Penn Comprehensive ALS Center at Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Weinberg ALS Center

Philadelphi, Pennsylvania, 19107, United States

Location

Related Publications (4)

• Sarasate M, Gonzalez N, Cordoba-Izquierdo A, Prats E, Gonzalez-Moro JMR, Marti S, Lujan M, Calle M, Anton A, Povedano M, Farrero E. Impact of Early Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis: A multicenter Randomized Controlled Trial. J Neuromuscul Dis. 2023;10(4):627-637. doi: 10.3233/JND-221658.

  PMID: 37212068 BACKGROUND

• Gruis KL, Brown DL, Weatherwax KJ, Feldman EL, Chervin RD. Evaluation of sham non-invasive ventilation for randomized, controlled trials in ALS. Amyotroph Lateral Scler. 2006 Jun;7(2):96-9. doi: 10.1080/14660820600640604.

  PMID: 16753973 BACKGROUND

• Ackrivo J, Hansen-Flaschen J, Wileyto EP, Schwab RJ, Elman L, Kawut SM. Development of a prognostic model of respiratory insufficiency or death in amyotrophic lateral sclerosis. Eur Respir J. 2019 Apr 18;53(4):1802237. doi: 10.1183/13993003.02237-2018. Print 2019 Apr.

  PMID: 30728207 BACKGROUND

• Ackrivo J, Hsu JY, Hansen-Flaschen J, Elman L, Kawut SM. Noninvasive Ventilation Use Is Associated with Better Survival in Amyotrophic Lateral Sclerosis. Ann Am Thorac Soc. 2021 Mar;18(3):486-494. doi: 10.1513/AnnalsATS.202002-169OC.

  PMID: 32946280 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Neuromuscular Diseases; Respiratory Insufficiency

Interventions

Noninvasive Ventilation; Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy; Positive-Pressure Respiration

Study Officials

• Jason T Ackrivo, MD, MSCE

  Perelman School of Medicine at the University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason T Ackrivo, MD, MSCE

CONTACT

215-829-3053; jason.ackrivo@pennmedicine.upenn.edu

Rebecca Lang Gallagher, MSEd

CONTACT

215-662-4088; Rebecca.Lang@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine and Neurology

Model Details: Pilot randomized clinical trial

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: July 17, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Upon study completion and for up to 3 years after study end date.
• Access Criteria: De-identified data available upon completion of a data sharing agreement

Locations

US (3)