Developing New Ways to Detect Respiratory Impairment Early in ALS

NCT07844590 — Recruiting, 70 participants, Thomas Jefferson University
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Early Detection of Respiratory Impairments in ALS: A Novel Diagnostic Approach

RegistryNCT07844590
StatusRecruiting
Study typeObservational
Enrollment70 (Estimated)
SponsorThomas Jefferson University (Other); collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
ConditionsAmyotrophic Lateral Sclerosis (ALS)
Datesstart 2026-09-01 (estimated), primary completion 2028-03-31 (estimated), completion 2028-03-31 (estimated), first posted 2026-09-28, last updated 2026-09-28
Locations1 site in United States

Related Papers Related Patents Related Grants Related Experts
All trials for Amyotrophic Lateral Sclerosis (ALS)

-Summary

The goal of this observational study is to develop new ways to detect early changes associated with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The study will examine whether changes in breathing, magnetic resonance imaging (MRI) of the brainstem and spinal cord, and blood markers can identify early signs of ALS before major physical changes occur.

The main questions the study aims to answer are:

* Can changes in automatic breathing help identify early ALS-related changes?
* Can breathing measures distinguish people with ALS from people without ALS?
* Do people with genetic risk for ALS who show changes in breathing also have changes in the brainstem and spinal cord or higher levels of blood markers associated with nerve damage?

Participants will complete breathing and muscle function tests, an MRI scan of the brainstem and spinal cord, and blood testing. The study will include people with ALS, people with genetic risk for ALS who do not yet have symptoms, and healthy adults for comparison.

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+Arms and interventions

ArmTypeInterventionsDescription
Symptomatic Amyotrophic Lateral SclerosisParticipants with symptomatic amyotrophic lateral sclerosis (ALS), including familial or sporadic ALS, who have clinical evidence of disease. This group will undergo study assessments to characterize respiratory function and biomarkers associated with ALS.
Asymptomatic/Presymptomatic ALS Gene CarriersParticipants who carry a genetic variant associated with amyotrophic lateral sclerosis but do not have clinical symptoms or functional deficits associated with ALS. This group will be evaluated for early or subclinical changes in respiratory function and other biomarkers associated with ALS.
Healthy ControlsNeurologically healthy participants without clinically identifiable neurological deficits who will serve as a comparison group for the study assessments.

+Outcome measures

Primary outcomes

  • Diagnostic Accuracy of the Automatic Breathing Impairment Risk Score (P0.1 + Chemosensitivity) for Detecting ALS-Related Respiratory Dysfunction [During the single study visit]: A linear prediction risk score combining airway occlusion pressure at 0.1 seconds (P0.1) and chemosensitivity will be developed to distinguish symptomatic ALS participants with respiratory dysfunction from healthy controls. Diagnostic performance of the risk score will be evaluated using the area under the receiver operating characteristic curve (ROC-AUC), and an optimal cutoff will be determined. The resulting cutoff will subsequently be used to identify subclinical respiratory impairment in asymptomatic/presymptomatic ALS gene carriers.

Secondary outcomes

  • Fractional Anisotropy of the Brainstem and Cervical Spinal Cord [During the single study visit]: Fractional anisotropy (FA) will be derived from diffusion tensor imaging of the brainstem and cervical spinal cord to evaluate microstructural abnormalities associated with ALS. FA will be compared among healthy controls and asymptomatic/presymptomatic ALS gene carriers who test positive or negative for automatic breathing impairment.
  • Axial Diffusivity of the Brainstem and Cervical Spinal Cord [During the single study visit]: Axial diffusivity will be derived from diffusion tensor imaging of the brainstem and cervical spinal cord to evaluate microstructural abnormalities associated with ALS. Measurements will be compared among healthy controls and asymptomatic/presymptomatic ALS gene carriers who test positive or negative for automatic breathing impairment.
  • Radial Diffusivity of the Brainstem and Cervical Spinal Cord [During the single study visit]: Radial diffusivity will be derived from diffusion tensor imaging of the brainstem and cervical spinal cord to evaluate microstructural abnormalities associated with ALS. Measurements will be compared among healthy controls and asymptomatic/presymptomatic ALS gene carriers who test positive or negative for automatic breathing impairment.
  • Mean Diffusivity of the Brainstem and Cervical Spinal Cord [During the single study visit]: Mean diffusivity will be derived from diffusion tensor imaging of the brainstem and cervical spinal cord to evaluate microstructural abnormalities associated with ALS. Measurements will be compared among healthy controls and asymptomatic/presymptomatic ALS gene carriers who test positive or negative for automatic breathing impairment.
  • Plasma Neurofilament Light Chain (Nf-L) Level [During the single study visit]: Neurofilament light chain (Nf-L) levels in plasma will be measured as a blood-based marker of neurodegeneration. Plasma Nf-L levels will be compared among healthy controls and asymptomatic/presymptomatic ALS gene carriers who test positive or negative for automatic breathing impairment to determine whether respiratory impairment is associated with greater evidence of neurodegeneration.
  • Serum Neurofilament Light Chain (Nf-L) Level [During the single study visit.]: Neurofilament light chain (Nf-L) levels in serum will be measured as a blood-based marker of neurodegeneration. Serum Nf-L levels will be evaluated in relation to automatic breathing impairment and compared across study groups as an additional blood-based biomarker of ALS-related neurodegeneration.

+Eligibility

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Symptomatic participants with ALS must have an ALS Functional Rating Scale-Revised (ALSFRS-R) score of 47/48 or less at the time of recruitment.
* Asymptomatic/presymptomatic participants must have a pathogenic C9orf72 expansion of at least 25 repeats or a similar genetic abnormality known to be associated with ALS.
* Healthy control participants must have no clinically identifiable neurological deficits based on medical history and screening. -

Exclusion Criteria:

* Any safety concern or contraindication to MRI based on MRI safety screening.
* Healthy control participants who do not pass the neurological screening.
* Pregnancy.
* Metal implants above the waist, including cardiac pacemakers or brain, neck, cervical, or thoracic implants.
* Neurocognitive impairment.
* Inability or unwillingness to provide informed consent.
* Younger than 18 years of age.

+Locations (1)

FacilityCityCountryStatus
Thomas Jefferson University - Center CityPhiladelphia, PennsylvaniaUnited StatesRecruiting

+Publications

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+Funding

NIH grants: R21NS145175