Clinical trial NCT06860347: Biomarkers for Fatigue in Patients with Myasthenia Gravis
Official title: Biomarkers for Fatigue in Patients with Myasthenia Gravis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myasthenia Gravis
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2025-03-06
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Myasthenia Gravis recruited after previous participation in the cross-sectional fatigue survey study (P15.287).

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


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

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.

Exclusion criteria for muscle biopsy

* The use of anticoagulants therapy.
* Allergy for lidocaine

Primary outcomes:
measure: blood biomarker
timeFrame: 2022
Secondary outcomes:
measure: Brain muscle axis
timeFrame: 2022-2023
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: Zuid-Holland
Study officials:
affiliation: Leiden University Medical Center
name: Martijn Tannemaat, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.