Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

T and B Cells in Graves' Orbitopathy (LYMPHGO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03195296
Recruitment Status : Completed
First Posted : June 22, 2017
Last Update Posted : February 12, 2018
Sponsor:
Information provided by (Responsible Party):
Marinò Michele, University of Pisa

Brief Summary:
Graves orbitopathy (GO) is an inflammatory eye disease associated in 95% of patients with Graves' hyperthyroidism (GH), in ~3-4% with hypothyroid autoimmune thyroiditis, and in ~1-2% with thyroid autoimmunity in the absence of thyroid dysfunction, the former known as euthyroid GO. The pathogenesis of GO is autoimmune, with the TSH-receptor being considered the major autoantigen, thereby establishing a pathogenetic link between the thyroid and orbital tissue. Thus, TSH-receptor is expressed by orbital fibroblasts, where it forms a complex with the IGF-1 receptor. Unlike GH, which is notoriously caused by TSH-receptor stimulating autoantibodies, GO is believed to reflect cell-mediated autoimmunity, as suggested by studies showing a Th1-like pattern of cytokine release by primary cultures of orbital infiltrating lymphocytes from GO patients. On the other hand, a role of B lymphocytes has emerged in recent years based on the observation that the anti-CD20 monoclonal antibody rituximab has a beneficial effect on GO activity, as demonstrated by a recent randomized clinical trial in which rituximab was compared with intravenous glucocorticoids (GC), being the former the standard treatment of moderately-severe GO. The explanation for the findings was that B lymphocytes are involved in the pathogenesis of GO as antigen-presenting cells. However, in spite of the above mentioned promising observations, another randomized clinical trial in which rituximab was compared with placebo provided opposite results. Thus, rituximab had no effect at all on GO. Data from the two studies were confronted and major differences between the two cohorts emerged, especially concerning GO activity, leading to the conclusion that rituximab may be effective for active, but not for inactive GO. Rituximab has been employed also for autoimmune diseases other than GO, including type 1 diabetes. In the former, it was shown that the effectiveness of rituximab paralleled the presence of CD20-positive infiltrating lymphocytes in pancreas islets. We therefore postulated that something similar may occur in GO, because of which we planned the present, perspective, observational study, aimed at determining the presence and immunohistochemical features of lymphocytes infiltrating orbital tissues in patients with GO and to relate them with the clinical features of GO.

Condition or disease Intervention/treatment
Graves Ophthalmopathy Other: No intervention

Layout table for study information
Study Type : Observational
Actual Enrollment : 20 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: T and B Cells Infiltrating Orbital Tissues in Graves' Orbitopathy (GO) and Their Relation With GO Features
Actual Study Start Date : January 1, 2017
Actual Primary Completion Date : May 31, 2017
Actual Study Completion Date : May 31, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eye Diseases

Group/Cohort Intervention/treatment
Graves' Orbitopathy
Patients with Graves' Orbitopathy subjected to orbital decompression
Other: No intervention
No intervention related to the study is foreseen




Primary Outcome Measures :
  1. Correlation between lymphocytes infiltrating orbital tissue and GO activity [ Time Frame: an average of 1 week ]

    Correlation between the number of lymphocytes infiltrating orbital tissues and the clinical activity score.

    The number of infiltrating lymphocytes is the sum of the number counted in four representative fields.

    The clinical activity score comprises 7 items (eyelid edema, conjuctival redness, eyelid redness, chemosis, caruncle edema, spontaneous eye pain, gaze-evoked eye pain), resulting in a numerical score going from 1 to 7



Secondary Outcome Measures :
  1. Correlation between CD3-positive lymphocytes infiltrating orbital tissue and GO activity [ Time Frame: an average of 1 week ]

    Correlation between the number of CD3-positive lymphocytes infiltrating orbital tissues and the clinical activity score.

    The number of CD3 positive infiltrating lymphocytes is the sum of the number counted in four representative fields, following immunohistochemical staining for CD3 The clinical activity score comprises 7 items (eyelid edema, conjuctival redness, eyelid redness, chemosis, caruncle edema, spontaneous eye pain, gaze-evoked eye pain), resulting in a numerical score going from 1 to 7


  2. Correlation between CD20-positive lymphocytes infiltrating orbital tissue and GO activity [ Time Frame: an average of 1 week ]

    Correlation between the number of CD20-positive lymphocytes infiltrating orbital tissues and the clinical activity score.

    The number of CD20 positive infiltrating lymphocytes is the sum of the number counted in four representative fields, following immunohistochemical staining for CD20 The clinical activity score comprises 7 items (eyelid edema, conjuctival redness, eyelid redness, chemosis, caruncle edema, spontaneous eye pain, gaze-evoked eye pain), resulting in a numerical score going from 1 to 7



Biospecimen Retention:   Samples Without DNA
Fibroadipose orbital tissue samples


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Consecutive patients with Graves' orbitopathy to undergo orbital decompression
Criteria

Inclusion Criteria:

  • Patients with Graves' orbitopathy subjected to orbital decompression

Exclusion Criteria:

  • None

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03195296


Sponsors and Collaborators
University of Pisa
Investigators
Layout table for investigator information
Principal Investigator: Michele Marinò, MD University of Pisa

Layout table for additonal information
Responsible Party: Marinò Michele, Ricercatore (Assistant Professor), University of Pisa
ClinicalTrials.gov Identifier: NCT03195296     History of Changes
Other Study ID Numbers: LYMPHGO
First Posted: June 22, 2017    Key Record Dates
Last Update Posted: February 12, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Graves Ophthalmopathy
Eye Diseases
Eye Diseases, Hereditary
Graves Disease
Exophthalmos
Orbital Diseases
Genetic Diseases, Inborn
Goiter
Thyroid Diseases
Endocrine System Diseases
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases