Intermuscular Coherence as a Biomarker for ALS

Amyotrophic Lateral Sclerosis Clinical Trial

— ALS-IMC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05104710
• Other study ID #: IRB20-1478
• Secondary ID: 1R01NS116262-01A
• Status: Recruiting
• Start date: March 31, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2023
• Source: University of Chicago
• Contact: Serdar Aydin, MD
• Phone: (773)795-9908
• Email: serdarmd[@]neurology.bsd.uchicago.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 650
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of California Center for Clinical Research	Irvine	California
United States	Washington University Medical Center	Saint Louis	Missouri

Sponsors (6)

Lead Sponsor	Collaborator
University of Chicago	Massachusetts General Hospital, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), University of California, Irvine, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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-ß? into the Awaji criteria improves the criteria's sensitivity for diagnosing ALS.	5 years
Secondary	Time to diagnosis of ALS	Aim 1 asks if incorporation of IMC-ß? into the Awaji criteria reduces the time to diagnosis of ALS.	5 years
Secondary	Rate of ALS disease progression	Aim 3 asks whether changes in the magnitude of IMC-ß? measured over many months varies with ALS disease progression in patients.	5 years

External Links

•   Intermuscular coherence in amyotrophic lateral sclerosis: A preliminary assessment