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

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

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.

Study Overview

• Status: Recruiting
• Conditions: 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 Type: Observational
• Enrollment (Estimated): 650

Contacts and Locations

• Study Contact: Name: Serdar Aydin, MD; Phone Number: (773)795-9908; Email: serdarmd@bsd.uchicago.edu

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • Active, not recruiting
      • University of California Center for Clinical Research
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Miller School of Medicine
      • Contact: Milagros Rodriguez; Phone Number: 305-243-6725; Email: mxr2872@med.miami.edu
      • Principal Investigator: Nathan Carrbery, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Sravan Mandepudi; Phone Number: 617-643-6036; Email: smandepudi@mgh.harvard.edu
      • Principal Investigator: Doreen A Ho, MD
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University Medical Center
      • Contact: Kelly McCoy-Gross; Phone Number: 314-273-8215; Email: kmccoygross@wustl.edu
      • Contact: Bethany Gannon; Phone Number: (314) 273-1686; Email: bgannon@wustl.edu
      • Principal Investigator: Sean S Smith, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-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 90 years old.

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

Description

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 90 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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to diagnosis of ALS	Aim 1 asks if incorporation of IMC-βγ into the Awaji criteria reduces the time to diagnosis of ALS.	5 years
Rate of ALS disease progression	Aim 3 asks whether changes in the magnitude of IMC-βγ measured over many months varies with ALS disease progression in patients.	5 years

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: Massachusetts General Hospital; Washington University School of Medicine; National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH); University of California, Irvine
• Investigators: Principal Investigator: Kourosh Rezania, MD, University of Chicago

Publications and helpful links

General Publications

• Issa NP, Frank S, Roos RP, Soliven B, Towle VL, Rezania K. Intermuscular coherence in amyotrophic lateral sclerosis: A preliminary assessment. Muscle Nerve. 2017 Jun;55(6):862-868. doi: 10.1002/mus.25426. Epub 2017 Feb 3.

Helpful Links

• Intermuscular coherence in amyotrophic lateral sclerosis: A preliminary assessment

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 21, 2021
• First Submitted That Met QC Criteria: October 21, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: ALS
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: IRB20-1478; 1R01NS116262-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO