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Reinnervation and Neuromuscular Transmission in ALS (RANTAL)

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ClinicalTrials.gov Identifier: NCT06219759
Recruitment Status : Recruiting
First Posted : January 23, 2024
Last Update Posted : January 25, 2024
Sponsor:
Collaborator:
Aarhus University Hospital
Information provided by (Responsible Party):
University of Aarhus

Study Description
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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.

Condition or disease Intervention/treatment
Amyotrophic Lateral Sclerosis Other: Observational study

Study Design
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Study Type : Observational
Estimated Enrollment : 120 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Reinnervation and Neuromuscular Transmission in Patients With Amyotrophic Lateral Sclerosis
Estimated Study Start Date : January 2024
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
ALS patients

Patients enrolled prior to determination of diagnosis on referral to neurophysiological examination. When the diagnosis is later established they get categorized as ALS patients.

ALS patients with recent diagnosis might also be included directly.

 Other: Observational study
Observational study.
ALS mimic disease patients
Patients enrolled prior to determination of diagnosis on referral to neurophysiological examination. When diagnosis is later established and the diagnosis is NOT ALS they get categorized as ALS mimic disease patients.
 Other: Observational study
Observational study.
Healthy controls
Healthy controls.
 Other: Observational study
Observational study.
Disease controls
Patients with another motor neuron disease than ALS with slow progression.
 Other: Observational study
Observational study.


Outcome Measures
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Primary Outcome Measures :
  1. Reinnervation [ Time Frame: From baseline and 8 months ]
    Difference between fast and slow progressing patients in change in mean amplitude size of motor units as estimated by MScanFit motor unit number estimation.

  2. Blood biomarkers [ Time Frame: Baseline ]
    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.

  3. Fatigue and decrement [ Time Frame: Baseline ]
    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.


Other Outcome Measures:
  1. Difference in mean amplitude size over time in patients. [ Time Frame: Baseline, 4 months and 8 months. ]
    Mean amplitude size measured by MScanFit technique.

  2. Difference in motor unit number estimation over time in patients. [ Time Frame: Baseline, 4 months and 8 months. ]
    Motor unit number estimation measured by MScanFit technique.

  3. Difference in mean amplitude size between patients and control groups [ Time Frame: Baseline. ]
    Mean amplitude size measured by MScanFit technique.

  4. Muscle strength assessed with manual muscle strength testing [ Time Frame: Baseline, 4 months and 8 months. ]
    Difference in measures from manual muscle strength testing.

  5. Difference in isometric ankle dorsiflexion strength measured on dynamometer. [ Time Frame: Baseline, 4 months and 8 months. ]
    Measured on dynamometer.

  6. Difference in handgrip strength measured on dynamometer. [ Time Frame: Baseline, 4 months and 8 months. ]
    Measured with handgrip dynamometer.

  7. Correlation between decrement at repetitive nerve stimulation and signs of reinnervation as measured by mean amplitude size. [ Time Frame: Baseline, 4 months and 8 months. ]
    Decrement measured with repetitive nerve stimulation and mean amplitude size measured with MScanFit technique.

  8. Blood concentration of c-terminal agrin fragment and neural cell adhesion molecule. [ Time Frame: Baseline, 4 months and 8 months. ]
    Difference in blood measurements of c-terminal agrin fragment, neural cell adhesion molecule, neurofilament light chain and routine kidney and liver markers.

  9. Difference in muscle thickness as measured by ultrasound examination of muscles [ Time Frame: Baseline, 4 months and 8 months. ]
    Measured by ultrasound examination.

  10. Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised scores [ Time Frame: Baseline, 4 months and 8 months. ]
    Difference in scores from Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Scale 0-48, with 48 being the best.

  11. Multidimensional Fatigue Inventory scores [ Time Frame: Baseline, 4 months and 8 months. ]
    Difference in scores from Multidimensional Fatigue Inventory. Scale 4-20, with 20 indicating worst degree of fatigue.

  12. Fatigue Severity Scale scores [ Time Frame: Baseline, 4 months and 8 months. ]
    Difference in scores from Fatigue Severity Scale. Scale 9-63, with 63 indicating worst degree of fatigue.

  13. Difference in free fatt mass as measured by bioelectrical impedance analysis. [ Time Frame: Baseline, 4 months and 8 months. ]
    Measured by bioelectrical impedance analysis.


Biospecimen Retention:   Samples With DNA
Blood samples stored for batch analysis.

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients refered for neurophysiological examination or patients followed at out-patient clinics.
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06219759


Contacts
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Contact: Jesper Storgaard, MD 004520231903 jesstg@rm.dk

Locations
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Denmark
Department of Neurology, Aarhus University Hospital Recruiting
Aarhus, Region Midtjylland, Denmark, 8200
Contact: Jesper H Storgaard, MD    004520231903    jesstg@rm.dk   
Sponsors and Collaborators
University of Aarhus
Aarhus University Hospital
Investigators
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Principal Investigator: Jesper H Storgaard, MD Aarhus University and Department of Neurology, Aarhus University Hospital
More Information
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Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT06219759    
Other Study ID Numbers: 8340
1-10-72-153-23 ( Other Identifier: Regional Research Ethics Committee Region Midtjylland )
First Posted: January 23, 2024    Key Record Dates
Last Update Posted: January 25, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
 Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases