Thymic Disease, Autoimmunity, and Neuromuscular Junction Integrity in Myasthenia Gravis

NCT07571525 | Not Yet Recruiting

• 1 other identifier: OSRSCP_TAILOR-MG
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

Myasthenia Gravis (MG); Myasthenia Gravis Associated With Thymoma; Thymoma

Keywords

myasthenia gravis; thymoma

Outcome Measures

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.

  At the time of thymectomy (baseline)

Secondary Outcomes (6)

• Qualitative assessment of thymic histopathological features

  At the time of thymectomy (baseline)

• Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) score

  Baseline, 6, 12, and 18 months

• Change in Quantitative Myasthenia Gravis (QMG) score

  Baseline, 6, 12, and 18 months

• Change in serum MG-related autoantibody levels over time

  Baseline, 6, 12, and 18 months

• Change in plasma and serum levels of complement activation products

  Baseline, 6, 12, and 18 months

Study Arms (4)

Patients with thymoma and MG-related antibodies

Patients with histologically or radiologically confirmed thymoma and presence of MG-related antibodies (AChR), with or without clinically manifest myasthenia gravis.

Patients with other thymic abnormalities and MG-related antibodies

Patients with non-thymomatous thymic pathology (e.g., thymic hyperplasia) and presence of MG-related antibodies (AChR), with or without clinically manifest myasthenia gravis.

Thymoma patients without MG-related antibodies

Patients with confirmed thymoma, negative for MG-related antibodies, and without clinical signs or diagnosis of myasthenia gravis.

Patients with established MG without thymic abnormalities

Patients with an established diagnosis of myasthenia gravis based on clinical, serological, and/or neurophysiological criteria, and no evidence of thymic abnormalities.

Eligibility Criteria

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

Study 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.

You may qualify if:

• 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
• Participants must also meet the criteria for at least one of the following study groups:
• Cohort 1: Thymoma with MG-related antibodies
• Histologically or radiologically confirmed thymoma
• Presence of at least one pathogenic MG-related antibody (AChR)
• Presence or absence of clinically manifest myasthenia gravis
• Cohort 2: Other thymic abnormalities with MG-related antibodies
• Imaging or histological evidence of non-thymomatous thymic pathology (e.g., thymic hyperplasia)
• Presence of at least one pathogenic MG-related antibody (AChR)
• Presence or absence of clinically manifest myasthenia gravis
• Cohort 3: Thymoma without MG-related antibodies
• Histologically or radiologically confirmed thymoma

You may not qualify if:

• 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
• Pregnancy or breastfeeding

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral blood samples (serum, plasma, and PBMCs) will be collected at baseline and follow-up visits, with aliquots retained for analysis of autoantibodies and immune biomarkers. In participants undergoing clinically indicated thymectomy, thymic tissue and residual intercostal muscle samples will be collected and retained for histological and molecular analyses of thymic pathology and neuromuscular junction structure.

MeSH Terms

Conditions

Myasthenia Gravis; Thymoma

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; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Thymus Neoplasms; Thoracic Neoplasms; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Stefano C Previtali

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stefano C Previtali

CONTACT

0039 0226433036; neuromuscolare@hsr.it

Benedetta Sorrenti

CONTACT

0039 0226433036; neuromuscolare@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Head Neuromuscular Repair Research Unit

Study Record Dates

• First Submitted: April 22, 2026
• First Posted: May 6, 2026
• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): September 14, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)