Immunological Follow-up of Patients With Basedow's Orbitopathy

NCT ID: NCT04610723

Last Updated: 2022-01-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 15 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-11-01
• Study Completion Date: 2021-11-30

Brief Summary

Graves' disease is characterized by the combination of anti-TSH receptor antibodies (Thyroid-Stimulating Hormone or thyroidotropic hormone), specific to this disease, with inconsistent symptoms such as hyperthyroidism, orbitopathy, goiter, or myxedema dermatological involvement. The activation of TSH receptors (RTSH) by these antibodies (known as "TRAK") causes the secretion of thyroid hormones as well as the development of the thyroid gland, responsible for a goiter. The cellular infiltrate responsible for the goiter consists mainly of T-lymphocytes but also of activated B lymphocytes secreting TRAK. Although Graves' disease is antibody mediated, cytokine secretion by Th1 therefore seems essential to pathogenesis. The treatment of orbitopathy requires primarily euthyroidism and the discontinuation of smoking. Despite these measures, moderate to severe attacks may require immunomodulatory treatment to limit local inflammation. This treatment is currently based on a first-line corticosteroid treatment (per os or preferably by weekly intravenous infusions). In the context of inadequate response, the therapeutic strategy is not very well established since some immunosuppressive treatments targeting B-cells or T- cells have been studied but with little benefit.

Many new concepts concerning immune tolerance and autoimmunity have emerged in recent years, particularly in Graves' disease, with sometimes complex cellular interactions. Certain mechanisms could occur either independently or in combination: i) modulation of T cell activation, differentiation and apoptosis; ii) inhibition of BL maturation and immunoglobulin production; iii) alteration of the balance between T helper (Th)-17 and T regulatory lymphocytes (Treg), by promoting Treg differentiation and inhibiting Th17 differentiation.

Conditions

Graves Orbitopathy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Patients aged 18 to 80 years included
• Subjects with Grave's disease and unsuccessful or intolerant to corticosteroid bolus therapy (EUGOGO protocol)
• Subjects with positive TRAKs

Exclusion Criteria

• Current treatment or within 6 months before inclusion by anti-CD20 monoclonal antibodies
• Current treatment or in the month prior to inclusion with corticosteroids >10 mg/day (oral or intravenous)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yves-Marie PERS, MD,PhD

Role: STUDY_DIRECTOR

University Hospital, Montpellier

Locations

Uhmontpellier

Montpellier, , France

Countries

France

Other Identifiers

RECHMPL20_0597

Identifier Type: -

Identifier Source: org_study_id