Developing New Ways to Detect Respiratory Impairment Early in ALS
maanantai 21. syyskuuta 2026 päivittänyt: Jayakrishnan Nair, Thomas Jefferson University
Early Detection of Respiratory Impairments in ALS: A Novel Diagnostic Approach
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.
Tutkimuksen yleiskatsaus
Tila
Rekrytointi
Opintotyyppi
Havainnollistava
Ilmoittautuminen (Arvioitu)
70
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskeluyhteys
- Nimi: Jayakrishnan Nair, PhD, PT
- Puhelinnumero: 352-871-5888
- Sähköposti: Jayakrishnan.Nair@jefferson.edu
Tutki yhteystietojen varmuuskopiointi
- Nimi: Dana Johnson, DPT
- Puhelinnumero: 215-326-9153
- Sähköposti: dana.johnson@jefferson.edu
Opiskelupaikat
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Pennsylvania
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Philadelphia, Pennsylvania, Yhdysvallat, 19107
- Rekrytointi
- Thomas Jefferson University - Center City
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Ottaa yhteyttä:
- Jayakrishnan Nair, PhD, PT
- Puhelinnumero: 352-871-5888
- Sähköposti: Jayakrishnan.Nair@jefferson.edu
-
Ottaa yhteyttä:
- Dana Johnson, DPT
- Puhelinnumero: 215-326-9153
- Sähköposti: Dana.Johnson@jefferson.edu
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Päätutkija:
- Jayakrishnan Nair, PhD, PT
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
18 vuotta ja vanhemmat (Aikuinen, Vanhempi Aikuinen)
Hyväksyy terveitä vapaaehtoisia
Joo
Sukupuolet, jotka voivat opiskella
Kaikki
Näytteenottomenetelmä
Ei-todennäköisyysnäyte
Tutkimusväestö
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.
Kuvaus
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.
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Havaintomallit: COHORT
- Aikanäkymät: PROSPECTIVE
Kohortit ja interventiot
Ryhmä/Kohortti |
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Symptomatic Amyotrophic Lateral Sclerosis
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. |
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Asymptomatic/Presymptomatic ALS Gene Carriers
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. |
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Healthy Controls
Neurologically healthy participants without clinically identifiable neurological deficits who will serve as a comparison group for the study assessments. |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Diagnostic Accuracy of the Automatic Breathing Impairment Risk Score (P0.1 + Chemosensitivity) for Detecting ALS-Related Respiratory Dysfunction
Aikaikkuna: During the single study visit
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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. |
During the single study visit
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Fractional Anisotropy of the Brainstem and Cervical Spinal Cord
Aikaikkuna: During the single study visit
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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. |
During the single study visit
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Axial Diffusivity of the Brainstem and Cervical Spinal Cord
Aikaikkuna: During the single study visit
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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. |
During the single study visit
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Radial Diffusivity of the Brainstem and Cervical Spinal Cord
Aikaikkuna: 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. |
During the single study visit
|
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Mean Diffusivity of the Brainstem and Cervical Spinal Cord
Aikaikkuna: 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. |
During the single study visit
|
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Plasma Neurofilament Light Chain (Nf-L) Level
Aikaikkuna: During the single study visit
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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. |
During the single study visit
|
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Serum Neurofilament Light Chain (Nf-L) Level
Aikaikkuna: During the single study visit.
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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. |
During the single study visit.
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Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Yhteistyökumppanit
Julkaisuja ja hyödyllisiä linkkejä
Tutkimusta koskevien tietojen syöttämisestä vastaava henkilö toimittaa nämä julkaisut vapaaehtoisesti. Nämä voivat koskea mitä tahansa tutkimukseen liittyvää.
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Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
- Magneettikuvaus
- Biomarkkerit
- keuhkojen toiminta
- Amyotrofinen lateraaliskleroosi
- Neurokuvantaminen
- Geneettinen riski
- Neurofilamentti kevyt ketju
- hengityslihasten voimaa
- Varhainen diagnoosi
- Lou Gehrigin tauti
- Aivorunko
- respiratory control
- hengitystoimintaa
- hypoksinen
- Hengityksen toiminta
- hyperkapninen
- Motorinen neuronien sairaus
- Pintaelektromyografia
- Selkäydin
- Hengityksen vajaatoiminta
- Respiratory biomarkers
- Presymptomatic amyotrophic lateral sclerosis
- Respiratory muscle function
- automatic breathing
- respiratory weakness
Muita asiaankuuluvia MeSH-ehtoja
- Keskushermoston sairaudet
- Hermoston sairaudet
- Patologiset prosessit
- Neuromuskulaariset sairaudet
- Metaboliset sairaudet
- Hengityselinten sairaudet
- Hengityshäiriöt
- Neurodegeneratiiviset sairaudet
- Merkit ja oireet, Hengityselimet
- Selkäydinsairaudet
- TDP-43 Proteinopatiat
- Proteostaasin puutteet
- Patologiset tilat, merkit ja oireet
- Ravitsemukselliset ja aineenvaihduntataudit
- Merkit ja oireet
- Hengityksen vajaatoiminta
- Sairaus
- Hengityshengitys
- Hypoksia
- Motorinen neuronitauti
- Amyotrofinen lateraaliskleroosi
- Hyperkapnia
- Charcot-Marie-hampaiden tauti, tyyppi 1F
Muut tutkimustunnusnumerot
- 22D.834
- 1R21NS145175-01A1 (Yhdysvaltain NIH-apuraha/sopimus)
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
JOO
IPD-suunnitelman kuvaus
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.
IPD-jaon aikakehys
Data will become available at the time of publication or by the end of the funding period, whichever occurs first. Data supporting a publication may be made available when the associated preprint is available. The duration of data preservation will be determined by the applicable repository and/or Thomas Jefferson University.
IPD-jaon käyttöoikeuskriteerit
De-identified data will be available to qualified investigators for research purposes. Requests for controlled-access data will be reviewed by a data-sharing committee for scientific merit and feasibility. A Data Use Agreement will be required before transfer of controlled-access data. Investigators receiving data must agree to use the data only for research purposes, not attempt to identify individual participants, and maintain appropriate data security. Public imaging datasets may be accessed through the applicable imaging repository.
IPD-jakamista tukeva tietotyyppi
- STUDY_PROTOCOL
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