Intermuscular Coherence: A Biomarker for Early Diagnosis and Follow-up of ALS

Study Purpose:

The specific aims of this study are to:

  1. Determine if a painless and quick measurement of muscle activity using surface electrodes can help with the diagnosis of ALS. Specifically, we ask if a measure of intermuscular coherence (IMC-βγ), when added to current diagnostic criteria (Awaji criteria), can differentiate ALS from mimic diseases more accurately and earlier than currently possible.
  2. Characterize IMC-βγ in neurotypical subjects by age, sex, race, and ethnicity.
  3. Follow a cohort of ALS patients longitudinally to determine if IMC-βγ changes with ALS disease progression and whether such changes correlate with functional and clinical scores, or survival.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS, Healthy Volunteer, Healthy Volunteer with a Family History of ALS

Study Type:

Observational Study

Study Category:

Biomarkers/Imaging

Study Status:

Enrolling

Phase:

Not Applicable

Study Chair(s)/Principal Investigator(s):

Kourosh Rezania, MD University of Chicago

Clinicaltrials.gov ID (11 digit #):

NCT05104710

Neals Affiliated?

No

Coordinating Center Contact Information

University of Chicago
Serdar Aydin, MD / .(JavaScript must be enabled to view this email address) / 773-795-9908
Shail Bhatnagar, MD / .(JavaScript must be enabled to view this email address) / 773-702-1124
United States

Full Study Summary:

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by neuronal death in the motor system, both in the brain and spinal cord. It results in progressive weakness throughout the body, and typically leads to respiratory failure 3-5 years after symptom onset. Therapy initiation and drug development are hindered, in part, by the lack of objective disease markers.

This is a multi-center trial to validate a potential biomarker for ALS, known as intermuscular coherence (IMC-βγ). IMC measures the correlation in the activity of two muscles during a simple motor task. In a preliminary study we found that patients with ALS have lower IMC than do control subjects. Because measuring IMC is quick, non-invasive, painless, and only requires equipment readily available in standard clinical neurophysiology labs, if validated it would be an important biomarker for ALS.

Study Sponsor:

University of Chicago

Participant Duration:

Estimated Enrollment:

650

Estimated Study Start Date:

03/31/2021

Estimated Study Completion Date:

12/31/2025

Posting Last Modified Date:

01/10/2022

Date Study Added to alsconsortium.org:

01/10/2022
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    20

    Maximum Age:

    80

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?

    Yes


    Study Population

    AIM 1: The study population includes patients with symptomatology suggestive of ALS who are referred to neuromuscular clinics at one of the four participating centers.

    AIM 2: All healthy subjects between 20 and 80 years old.

    AIM 3: Patients with suspected ALS who had an initially detectible IMC-βγ.

    Criteria

    Inclusion Criteria:

    AIM 1: Patients with arm or leg weakness, spastic gait, muscle wasting and/or fasciculations (muscle twitching), dysphagia (difficulty swallowing), dysarthria (difficulty speaking), shortness of breath, hyperreflexia or pathological reflexes, or findings of muscle denervation in previous needle electromyography (EMG) studies.
    AIM 2: Subjects between 20 and 80 years of age.
    AIM 3: Subjects will be selected from among Aim 1 patients who carry an Awaji (without IMC) category of Possible, Probable, or Definite ALS.

    Exclusion Criteria:

    AIM 1:

    • Classified as probable or definite ALS by Awaji criteria prior to initial study evaluation
    • Have significant sensory loss in the weak or spastic limbs
    • Have significant musculoskeletal or neuropathic pain
    • Have an inability or are unwilling to provide informed consent
    • Are unable to perform the study-related task
    • Are taking baclofen or benzodiazepines
    • Have a known non-ALS cause for symptoms

    AIM 2:

    • Have a history of neurological disorders such as stroke, neuropathy, or myopathy
    • Have significant pain or sensory loss
    • Are taking baclofen or sedatives such as benzodiazepines
    • Lack of cognitive ability or willingness to provide informed consent

    AIM 3:

    • Were unclassified according to the Awaji category or had a defined ALS mimic
    • Are taking baclofen, sedatives or benzodiazepines.

    NOTE: Participation in a therapeutic clinical trial is NOT an exclusion criterion since this study would not interfere with any potential interventions.

  • Site Contact Information

    University of California
    Jennifer Avelar / .(JavaScript must be enabled to view this email address) / 714-509-2665
    Jeanette Overton / .(JavaScript must be enabled to view this email address) / 714-456-8520
    Irvine, California 92697
    United States

    Massachusetts General Hospital
    Grace Addy / .(JavaScript must be enabled to view this email address) / 617-726-4282
    Geli Kane / .(JavaScript must be enabled to view this email address) / 617-726-1531
    Boston, Massachusetts 02114
    United States

    Washington University Medical Center
    Kelly McCoy-Gross / .(JavaScript must be enabled to view this email address) / 314-273-8215
    Sukrutha Thotala / .(JavaScript must be enabled to view this email address) / 314-273-7966
    Saint Louis, Missouri 63110
    United States