Intermuscular Coherence as a Biomarker for ALS

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis

• Registration Number: NCT05104710
• Lead Sponsor: University of Chicago

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.

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 Timeline

• Study Start: 2021-03-31
• Study First Submitted: 2021-10-21
• Study First Submitted QC: 2021-10-21
• Study First Posted: 2021-11-03
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-02
• Last Update Posted: 2024-08-06
• Primary Completion: 2025-06-30
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 650

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in the sensitivity for diagnosing ALS when a measure of intermuscular coherence is added to the Awaji criteria.	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

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

Trial Locations

Locations (4)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Miami Miller School of Medicine; 🇺🇸 Miami, Florida, United States

Washington University Medical Center; 🇺🇸 Saint Louis, Missouri, United States

University of California Center for Clinical Research; 🇺🇸 Irvine, California, United States