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Intermuscular Coherence as a Biomarker for ALS (ALS-IMC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05104710
Recruitment Status : Recruiting
First Posted : November 3, 2021
Last Update Posted : November 5, 2021
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Massachusetts General Hospital
Washington University School of Medicine
University of California, Irvine
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
University of Chicago

Study Description
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Brief Summary:

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.

Condition or disease
Amyotrophic Lateral Sclerosis

Detailed Description:

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 Design
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Study Type : Observational
Estimated Enrollment : 650 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Intermuscular Coherence: A Biomarker for Early Diagnosis and Follow-up of ALS
Actual Study Start Date : March 31, 2021
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort
AIM 1

Hypothesis: IMC-βγ can help to differentiate between ALS and mimic diseases at initial presentation.

Patients who present to a neuromuscular clinic with symptoms that might be from ALS but for whom a diagnosis is not yet known, will be studied. Measurements of intermuscular coherence will be made using surface electrodes. A standard neurological examination and questionnaire about ALS symptoms will be completed. No interventions will be made. A patient's final diagnosis will be determined using standard-of-care testing. Six months after initial IMC measurement, a determination will be made whether the IMC predicted the diagnosis of ALS.
AIM 2

Hypothesis: Characterization of demographic-specific distributions will improve the specificity of IMC-βγ for ALS.

To optimize cutoff values for abnormal IMC, IMC-βγ will be measured in neurotypical controls across a range of age, race, ethnicity, and sexes.
AIM 3

Hypothesis: IMC-βγ will decrease with disease progression.

Because IMC-βγ measures functional input from motor neurons in the brain, it should decrease as these neurons are lost. IMC will be measured sequentially about every 3 months in patients with ALS, and will be compared to measures of clinical progression.


Outcome Measures
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Primary Outcome Measures :
  1. Change in the sensitivity for diagnosing ALS when a measure of intermuscular coherence is added to the Awaji criteria. [ Time Frame: 5 years ]
    Aim 1 asks if incorporation of IMC-βγ into the Awaji criteria improves the criteria's sensitivity for diagnosing ALS.


Secondary Outcome Measures :
  1. Time to diagnosis of ALS [ Time Frame: 5 years ]
    Aim 1 asks if incorporation of IMC-βγ into the Awaji criteria reduces the time to diagnosis of ALS.

  2. Rate of ALS disease progression [ Time Frame: 5 years ]
    Aim 3 asks whether changes in the magnitude of IMC-βγ measured over many months varies with ALS disease progression in patients.


Eligibility Criteria
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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
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:

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

  • AIM 2:

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

  • AIM 3:

    1. Were unclassified according to the Awaji category or had a defined ALS mimic
    2. 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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05104710


Contacts
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Contact: Serdar Aydin, MD (773)795-9908 serdarmd@neurology.bsd.uchicago.edu
Contact: Shail Bhatnagar, MD (773)702-1124 sbhatnagar@neurology.bsd.uchicago.edu

Locations
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United States, California
University of California Center for Clinical Research Recruiting
Irvine, California, United States, 92697
Contact: Jennifer Avelar    714-509-2665    jbavelar@hs.uci.edu   
Contact: Jeanette Overton    (714)456-8520    jtoverto@hs.uci.edu   
Principal Investigator: Ali A Habib, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Grace Addy    617-726-4282    gaddy@mgh.harvard.edu   
Contact: Geli Kane    (617) 726-1531    gckane@mgh.harvard.edu   
Principal Investigator: William S David, MD         
United States, Missouri
Washington University Medical Center Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Kelly McCoy-Gross    314-273-8215    kmccoygross@wustl.edu   
Contact: Sukrutha Thotala    (314) 273-7966    thotala.s@wustl.edu   
Principal Investigator: Robert Bucelli, MD         
Sponsors and Collaborators
University of Chicago
National Institutes of Health (NIH)
Massachusetts General Hospital
Washington University School of Medicine
University of California, Irvine
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Kourosh Rezania, MD University of Chicago
More Information
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Additional Information:

Publications of Results:

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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT05104710    
Other Study ID Numbers: IRB20-1478
1R01NS116262-01A1 ( U.S. NIH Grant/Contract )
First Posted: November 3, 2021    Key Record Dates
Last Update Posted: November 5, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of Chicago:
ALS
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
 Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases