Reinnervation and Neuromuscular Transmission in ALS

Amyotrophic Lateral Sclerosis Clinical Trial

— RANTAL  

Official title:

Reinnervation and Neuromuscular Transmission in Patients With Amyotrophic Lateral Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06219759
• Other study ID #: 8340
• Secondary ID: 1-10-72-153-23
• Status: Recruiting
• Start date: May 2024
• Est. completion date: December 2026

Study information

• Verified date: January 2024
• Source: University of Aarhus
• Contact: Jesper Storgaard, MD
• Phone: 004520231903
• Email: jesstg[@]rm.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Other:
• Observational study
Observational study.

Locations

Country	Name	City	State
Denmark	Department of Neurology, Aarhus University Hospital	Aarhus	Region Midtjylland

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Difference in mean amplitude size over time in patients.	Mean amplitude size measured by MScanFit technique.	Baseline, 4 months and 8 months.
Other	Difference in motor unit number estimation over time in patients.	Motor unit number estimation measured by MScanFit technique.	Baseline, 4 months and 8 months.
Other	Difference in mean amplitude size between patients and control groups	Mean amplitude size measured by MScanFit technique.	Baseline.
Other	Muscle strength assessed with manual muscle strength testing	Difference in measures from manual muscle strength testing.	Baseline, 4 months and 8 months.
Other	Difference in isometric ankle dorsiflexion strength measured on dynamometer.	Measured on dynamometer.	Baseline, 4 months and 8 months.
Other	Difference in handgrip strength measured on dynamometer.	Measured with handgrip dynamometer.	Baseline, 4 months and 8 months.
Other	Correlation between decrement at repetitive nerve stimulation and signs of reinnervation as measured by mean amplitude size.	Decrement measured with repetitive nerve stimulation and mean amplitude size measured with MScanFit technique.	Baseline, 4 months and 8 months.
Other	Blood concentration of c-terminal agrin fragment and neural cell adhesion molecule.	Difference in blood measurements of c-terminal agrin fragment, neural cell adhesion molecule, neurofilament light chain and routine kidney and liver markers.	Baseline, 4 months and 8 months.
Other	Difference in muscle thickness as measured by ultrasound examination of muscles	Measured by ultrasound examination.	Baseline, 4 months and 8 months.
Other	Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised scores	Difference in scores from Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Scale 0-48, with 48 being the best.	Baseline, 4 months and 8 months.
Other	Multidimensional Fatigue Inventory scores	Difference in scores from Multidimensional Fatigue Inventory. Scale 4-20, with 20 indicating worst degree of fatigue.	Baseline, 4 months and 8 months.
Other	Fatigue Severity Scale scores	Difference in scores from Fatigue Severity Scale. Scale 9-63, with 63 indicating worst degree of fatigue.	Baseline, 4 months and 8 months.
Other	Difference in free fatt mass as measured by bioelectrical impedance analysis.	Measured by bioelectrical impedance analysis.	Baseline, 4 months and 8 months.
Primary	Reinnervation	Difference between fast and slow progressing patients in change in mean amplitude size of motor units as estimated by MScanFit motor unit number estimation.	From baseline and 8 months
Primary	Blood biomarkers	Difference in blood concentration of c-terminal agrin fragment and neural cell adhesion molecule at baseline between ALS patients, healthy controls and ALS mimic disease patients.	Baseline
Primary	Fatigue and decrement	Difference in proportion of participants with decrement between ALS patients and ALS mimic disease patients as well as degree of fatigue among ALS patients with and without neuromuscular transmission deficiency.	Baseline