Clinical trial NCT05104710: Intermuscular Coherence as a Biomarker for ALS
Official title: Intermuscular Coherence: A Biomarker for Early Diagnosis and Follow-up of ALS
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Massachusetts General Hospital
name: Washington University School of Medicine
name: University of California, Irvine
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2021-11-03
Enrollment: 650
Sex: ALL
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility 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 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.

Primary outcomes:
measure: Change in the sensitivity for diagnosing ALS when a measure of intermuscular coherence is added to the Awaji criteria.
timeFrame: 5 years
Secondary outcomes:
measure: Time to diagnosis of ALS
timeFrame: 5 years
measure: Rate of ALS disease progression
timeFrame: 5 years
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Center for Clinical Research
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University Medical Center
state: Missouri
Study officials:
affiliation: University of Chicago
name: Kourosh Rezania, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.