Thymic Disease, Autoimmunity, and Neuromuscular Junction Integrity in Myasthenia Gravis
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorIRCCS San Raffaele
About this trial
The goal of this observational study is to investigate the clinical, immunological, and neuromuscular features associated with the development and progression of myasthenia gravis (MG) in adult patients with thymic abnormalities and/or MG-related antibodies, including individuals with or without clinically manifest disease.
The main questions it aims to answer are:
* Whether integrated clinical, serological, and histopathological profiles are associated with the presence of MG and can predict disease onset or progression * Wheter systemic immune markers are associated with disease activity, progression, and neuromuscular junction alterations
Participants will:
* Undergo clinical, neurological, and neurophysiological assessments at baseline and during follow-up * Provide blood samples for serological and immunological analyses * Provide thymic tissue and residual intercostal muscle samples (when undergoing clinically indicated thymectomy) for research analyses * Attend follow-up visits at 6, 12, and 18 months * Record daily symptoms using an electronic patient-reported outcome tool (for participants with MG)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years at the time of informed consent
Ability to provide written informed consent and comply with study procedures
Availability of a serum sample for testing MG-related antibodies
Availability of chest imaging (CT and/or MRI) to classify thymic status
Disqualifiers
Inability to provide informed consent
Other neuromuscular diseases that could interfere with interpretation of clinical or neurophysiological findings
Severe uncontrolled systemic illness that, in the investigator's judgment, may limit participation or confound study outcomes
Any medical or psychiatric condition, or history of substance abuse, that may compromise adherence to study procedures
Trial population
The study population consists of adult patients (≥18 years) undergoing evaluation for thymic abnormalities and/or myasthenia gravis at a tertiary referral center. Participants include individuals with thymoma or other thymic pathology, with or without MG-related antibodies and with or without clinically manifest myasthenia gravis, as well as patients with established myasthenia gravis without evidence of thymic abnormalities. Participants are recruited from routine clinical care settings, including neurology and thoracic surgery units, and reflect a spectrum of clinical and immunological phenotypes relevant to disease development and progression. This population enables the investigation of the relationship between thymic pathology, systemic immune profiles, and neuromuscular junction involvement in myasthenia gravis.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
40 Participants
are grouped into 4 trial groupsGroup A: Patients with thymoma and MG-related antibodies
Group B: Patients with other thymic abnormalities and MG-related antibodies
Group C: Thymoma patients without MG-related antibodies
Group D: Patients with established MG without thymic abnormalities
Trial outcomes
Primary outcomes
1
Qualitative assessment of neuromuscular junction structural abnormalities in intercostal muscle samples
The primary outcome is the qualitative assessment of neuromuscular junction structural abnormalities in residual intercostal muscle samples collected from participants undergoing clinically indicated thymectomy. Neuromuscular junction integrity will be evaluated using histological, immunofluorescence, and ultrastructural analyses, including assessment of acetylcholine receptor clustering, IgG and complement deposition, postsynaptic fold morphology, and features of synaptic remodeling or immune-mediated injury. Structural abnormalities will be described in terms of presence or absence and, where applicable, semi-quantitative grading. Findings will be compared across participant groups according to thymic pathology, MG-related antibody status, and the presence or absence of clinically manifest myasthenia gravis.
Time frame
At the time of thymectomy (baseline)Secondary outcomes
1
Qualitative assessment of thymic histopathological features
Qualitative assessment of thymic histopathological features in thymic tissue collected from participants undergoing clinically indicated thymectomy. Thymic tissue will be evaluated for histopathological features including thymoma subtype, thymic hyperplasia, germinal centers, lymphoid infiltrates, and AIRE expression, where applicable. Histopathological findings will be described in terms of presence or absence and, where applicable, semi-quantitative grading. These features will be analyzed in relation to neuromuscular junction structural abnormalities identified in intercostal muscle samples, as well as according to MG-related antibody status and the presence or absence of clinically manifest myasthenia gravis.
Time frame
At the time of thymectomy (baseline)2
Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) score
The MG-ADL is an 8-item scale assessing myasthenia gravis-related symptoms and functional impairment, with a total score ranging from 0 to 24. Higher scores indicate greater disease burden. Changes from baseline will be evaluated during follow-up and analyzed in relation to biological markers, neuromuscular junction findings, and electronically collected patient-reported symptom scores.
Time frame
Baseline, 6, 12, and 18 months3
Change in Quantitative Myasthenia Gravis (QMG) score
The QMG is a 13-item examiner-administered scale assessing muscle weakness and fatigability, with a total score ranging from 0 to 39. Higher scores indicate greater disease severity. Changes from baseline will be evaluated during follow-up and analyzed in relation to biological markers, neuromuscular junction findings, and electronically collected patient-reported symptom scores.
Time frame
Baseline, 6, 12, and 18 months4
Change in serum MG-related autoantibody levels over time
Measurement of serum levels of MG-related autoantibodies, including acetylcholine receptor (AChR) antibodies, assessed using cell-based assays and ELISA assays. Autoantibody levels will be reported as titers and evaluated at baseline and during follow-up to describe their distribution and longitudinal changes. These measurements will be analyzed in relation to clinical and neurophysiological findings, as well as thymyc histopathology and neuromuscular junction structural features.
Time frame
Baseline, 6, 12, and 18 monthsSponsors and contacts
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Source ClinicalTrials.gov
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