Developing New Ways to Detect Respiratory Impairment Early in ALS
ConditionAmyotrophic Lateral Sclerosis (ALS)
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorThomas Jefferson University
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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. -
Disqualifiers
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.
Trial population
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.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
70 Participants
are grouped into 3 trial groupsGroup A: Symptomatic Amyotrophic Lateral Sclerosis
Group B: Asymptomatic/Presymptomatic ALS Gene Carriers
Group C: Healthy Controls
Trial outcomes
Primary outcomes
1
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 visitSecondary outcomes
1
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 visit2
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 visit3
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 visit4
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 visitSponsors and contacts
Click on the lead sponsor to view all of their trials.
Thomas Jefferson University
Lead sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
Collaborator
Source ClinicalTrials.gov