Intermuscular Coherence as a Biomarker for ALS

NCT05104710 | Recruiting

• 2 other identifiers: IRB20-14781R01NS116262-01A1
• Study Type: observational
• Target: 650
• Locations: 1 country
• Sites: 4

Brief Summary

The specific aims of this study are to:

1. 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. 2.Characterize IMC-βγ in neurotypical subjects by age, sex, race, and ethnicity.
3. 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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Time to diagnosis of ALS

  5 years

• Rate of ALS disease progression

  5 years

Study Arms (3)

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.

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: collaborator
• University of California, Irvine: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• University of Chicago: lead
• Massachusetts General Hospital: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (4)

University of California Center for Clinical Research

Irvine, California, 92697, United States

ACTIVE NOT RECRUITING

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Washington University Medical Center

St Louis, Missouri, 63110, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 27699797 RESULT

Related Links

• Intermuscular coherence in amyotrophic lateral sclerosis: A preliminary assessment

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Kourosh Rezania, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Serdar Aydin, MD

CONTACT

(773)795-9908; serdarmd@bsd.uchicago.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2021
• First Posted: November 3, 2021
• Study Start: March 31, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)