Biomarkers for Fatigue in Patients with Myasthenia Gravis

NCT06860347 | Completed DMC

• 1 other identifier: NL72266.058.20
• Study Type: observational
• Target: 115
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Myasthenia Gravis (MG) is a chronic autoimmune disease affecting the neuromuscular junction. Although a hallmark of MG is muscle fatigability due to dysfunction of the neuromuscular junction (peripheral fatigue), a large number of MG patients also report symptoms of central or cognitive fatigue. Central fatigue is defined as an experienced lack of energy, physically and/or mentally. In October 2019 we performed a cross-sectional survey study (P15.287) among 420 Dutch MG patients showing a clinically relevant central fatigue rate of 62% on the Checklist Individual Strength-Fatigue subscale (CIS-f). In this prior study, we identified a number of factors associated with fatigue, but these factors cannot fully explain the observed high prevalence of fatigue in MG and very little is known on its biological substrates and pathophysiology. Objectives: The main objective is to investigate if there are biomarkers for fatigue in MG. The secondary objective is to investigate the muscle origin of these biomarkers. Study design: This study will be an exploratory study, subdivided in part I and part II (optional). Study population: Patients with Myasthenia Gravis recruited after previous participation in the cross-sectional fatigue survey study (P15.287). Intervention: Phase I: Visit 1, time: 0

• blood withdrawal
• muscle biopsy (not mandatory for participation)
• QMG
• questionnaires on medication, disease severity, fatigue, depressive symptoms and physical condition Phase II (optional): Visit 2, time: 6-12 months after visit 1, after analysis of phase I results.
• blood withdrawal (similar analysis as phase I)
• QMG
• questionnaires on medication, disease severity, fatigue, depressive symptoms and physical condition

Conditions

Myasthenia Gravis

Outcome Measures

Primary Outcomes (1)

• blood biomarker

  To investigate whether there is a potential biomarker, which corresponds with fatigue in MG, among the biomarkers that were previously identified in other disorders. For this objective we aim to determine and compare the diagnostic yield of several serum biomarkers which were (possibly) associated with central fatigue in other disorders in previous studies.

  2022

Secondary Outcomes (1)

• Brain muscle axis

  2022-2023

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Myasthenia Gravis recruited after previous participation in the cross-sectional fatigue survey study (P15.287).

You may qualify if:

• Male of female patients aged ≥ 18 years
• Subjects must understand the requirements of the study and provide written informed consent.
• Diagnosis of MG:
• Clinical signs or symptoms characteristic for MG and
• A positive serologic test for AChR antibodies

You may not qualify if:

• A medical history of other active auto-immune disorders for which the patient currently receives a medical treatment, such as thyroid disease or rheumatoid arthritis.
• A medical history of neoplasms within the last year.
• Substance abuse.
• The use of anticoagulants therapy.
• Allergy for lidocaine

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333ZA, Netherlands

Location

Related Publications (2)

• Ruiter AM, Verschuuren JJGM, Tannemaat MR. Prevalence and associated factors of fatigue in autoimmune myasthenia gravis. Neuromuscul Disord. 2021 Jul;31(7):612-621. doi: 10.1016/j.nmd.2021.04.002. Epub 2021 Apr 24.

  PMID: 34034925 BACKGROUND

• Ruiter AM, Verschuuren JJGM, Tannemaat MR. Fatigue in patients with myasthenia gravis. A systematic review of the literature. Neuromuscul Disord. 2020 Aug;30(8):631-639. doi: 10.1016/j.nmd.2020.06.010. Epub 2020 Jul 1.

  PMID: 32718868 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and muscle biopsy

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Martijn Tannemaat, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: August 3, 2022
• First Posted: March 6, 2025
• Study Start: May 19, 2022
• Primary Completion: September 1, 2022
• Study Completion: April 1, 2023
• Last Updated: March 6, 2025

Record last verified: 2025-03

Locations

NL (1)