Clinical trial NCT06219759: Reinnervation and Neuromuscular Transmission in ALS
Official title: Reinnervation and Neuromuscular Transmission in Patients With Amyotrophic Lateral Sclerosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2024-01-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients refered for neurophysiological examination or patients followed at out-patient clinics.

Brief summary: The aim of this study is to describe the changes in the neuromuscular connection in patients with amyotrophic lateral sclerosis (ALS). The study consist of three substudies that have the following main hypothesis:

1. that ALS patients do not demonstrate equal capacity for muscle reinnervation and that reinnervation preserves muscle function and thereby slows down progression.
2. that blood concentrations of c-terminal agrin fragment (bCAF) reflect neuromuscular transmission deficiency and that blood concentration of neural cell adhesion molecule reflects degree of muscle denervation in patients.
3. that ALS patients with decrement when examined with repetitive nerve stimulation have more physical fatigue, slower progression, higher degree of reinnervation and higher bCAF compared to ALS patients without decrement.

There will be 3 inclusion groups.

1. patients referred for neurophysiological examination on suspicion of motor neuron disease.
2. healthy controls
3. disease control: patients with another motor neuron disease with slow progression.

All participants will be invited for at least 1 visit (baseline). If participants in group 1 eventually receive the diagnosis of ALS they will be invited for 2 additional visits 4 og 8 months after baseline visit, respectively.

Examinations will consist of:

* nerve conduction study
* repetitive nerve stimulation (except for healthy controls) to examine impairment of the neuromuscular connection.
* motor unit number estimation with MScanFit to estimate number and size of motor units.
* ultrasound examination of muscles to measure size and condition of muscles.
* questionnaires on fatigue and functional status.
* blood sample for measurement of specialized analysis (c-terminal agrin fragment and neural cell adhesion molecule) and routine analysis (liver and kidney function as well as neurofilament light chain)
* muscle strength assessment manually and by dynamometer to follow progression of muscle weakness
* bioelectrical impedance measurement to follow the overall body composition.


Eligibility criteria: Inclusion Criteria:

* Referred to clinical neurophysiological examination on suspicion of motor neuron disease or diagnosed with ALS according to Gold Coast criteria within the last 3 months.
* Age ≥18 years old
* Able and willing to provide informed consent

Exclusion Criteria:

* Former central or peripheral nervous system disease
* Diabetes
* Electrophysiological signs of polyneuropathy at baseline visit
* Pacemaker
* Pregnancy

For disease controls the exclusion criteria are the same, but the inclusion criteria:

* Diagnosed with disease with slow, progressive loss of motor neurons
* Age ≥18 years old
* Able and willing to provide informed consent

Primary outcomes:
measure: Reinnervation
timeFrame: From baseline and 8 months
measure: Blood biomarkers
timeFrame: Baseline
measure: Fatigue and decrement
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
measure: Difference in mean amplitude size over time in patients.
timeFrame: Baseline, 4 months and 8 months.
measure: Difference in motor unit number estimation over time in patients.
timeFrame: Baseline, 4 months and 8 months.
measure: Difference in mean amplitude size between patients and control groups
timeFrame: Baseline.
measure: Muscle strength assessed with manual muscle strength testing
timeFrame: Baseline, 4 months and 8 months.
measure: Difference in isometric ankle dorsiflexion strength measured on dynamometer.
timeFrame: Baseline, 4 months and 8 months.
measure: Difference in handgrip strength measured on dynamometer.
timeFrame: Baseline, 4 months and 8 months.
measure: Correlation between decrement at repetitive nerve stimulation and signs of reinnervation as measured by mean amplitude size.
timeFrame: Baseline, 4 months and 8 months.
measure: Blood concentration of c-terminal agrin fragment and neural cell adhesion molecule.
timeFrame: Baseline, 4 months and 8 months.
measure: Difference in muscle thickness as measured by ultrasound examination of muscles
timeFrame: Baseline, 4 months and 8 months.
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised scores
timeFrame: Baseline, 4 months and 8 months.
measure: Multidimensional Fatigue Inventory scores
timeFrame: Baseline, 4 months and 8 months.
measure: Fatigue Severity Scale scores
timeFrame: Baseline, 4 months and 8 months.
measure: Difference in free fatt mass as measured by bioelectrical impedance analysis.
timeFrame: Baseline, 4 months and 8 months.
Locations:
city: Aarhus
country: Denmark
facility: Department of Neurology, Aarhus University Hospital
state: Region Midtjylland
Study officials:
affiliation: Aarhus University and Department of Neurology, Aarhus University Hospital
name: Jesper H Storgaard, MD
role: PRINCIPAL_INVESTIGATOR
References: