An observational study in Amyotrophic Lateral Sclerosis (ALS), sponsored by Thomas Jefferson University. Recruiting at 1 site in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Thomas Jefferson University · Observational
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:
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.
The study population will include adults with symptomatic ALS, asymptomatic or presymptomatic individuals with genetic variants associated with ALS, and healthy age- and sex-matched controls. Participants with ALS or genetic risk for ALS will be recruited from Thomas Jefferson University and other ALS patient inventories and referral sources.
Exclusion Criteria:
Participants 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.
Participants 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.
Neurologically healthy participants without clinically identifiable neurological deficits who will serve as a comparison group for the study assessments.
Diagnostic Accuracy of the Automatic Breathing Impairment Risk Score (P0.1 + Chemosensitivity) for Detecting ALS-Related Respiratory Dysfunction
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.
Time frame: During the single study visit
Fractional Anisotropy of the Brainstem and Cervical Spinal Cord
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.
Time frame: During the single study visit
Axial Diffusivity of the Brainstem and Cervical Spinal Cord
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.
Time frame: During the single study visit
Radial Diffusivity of the Brainstem and Cervical Spinal Cord
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.
Time frame: During the single study visit
Mean Diffusivity of the Brainstem and Cervical Spinal Cord
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.
Time frame: During the single study visit
Plasma Neurofilament Light Chain (Nf-L) Level
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.
Time frame: During the single study visit
Serum Neurofilament Light Chain (Nf-L) Level
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.
Time frame: During the single study visit.
Plan to share: Yes — De-identified individual participant data underlying the results reported in study publications will be shared. Data may include demographic and clinical data, functional respiratory measurements, brainstem and spinal cord MRI data, and blood biomarker data, including neurofilament light chain measurements. Data will be shared without direct participant identifiers and in accordance with applicable data use agreements and institutional requirements.
Supporting information: Study protocol
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Amyotrophic Lateral Sclerosis→
Thomas Jefferson University