Immunological Follow-up of Patients With Basedow's Orbitopathy

Graves Orbitopathy Clinical Trial

— SIPO  

Official title:

Immunological Follow-up of Patients With Basedow's Orbitopathy : SIPO

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04610723
• Other study ID #: RECHMPL20_0597
• Status: Completed
• Start date: November 1, 2020
• Est. completion date: November 30, 2021

Study information

• Verified date: January 2022
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: November 30, 2021
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Graves Ophthalmopathy
• Graves Orbitopathy

Locations

Country	Name	City	State
France	Uhmontpellier	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantify the subpopulations of CD4, CD8, Th, Treg and B-cells	Quantify the subpopulations of CD4, CD8, Th, Treg and B-cells in the peripheral blood of subjects with Graves' disease	1 day
Secondary	Compare the frequency and activation of lymphocyte subpopulations	Compare the frequency and activation of lymphocyte subpopulations in peripheral blood regarding TRAK levels	1 day
Secondary	Compare the phenotypic characteristics of Tregs present	Compare the phenotypic characteristics of Tregs present in the peripheral blood of Graves' disease patients with Tregs in the peripheral blood of RA patients (previous laboratory data).	1 day