An observational study in Thyroid Eye Disease, sponsored by University of Pittsburgh. Terminated at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2019-11-18.
Sponsored by University of Pittsburgh · Observational
Thyroid eye disease (TED) is an autoimmune inflammation of the orbital tissues that develops in up to 50% of patients with Graves' disease. Although about 80% respond to IVGC initially, the relapse rate is high and about 75% require further surgery despite initial response. Although the natural history of TED is associated with spontaneous remissions after about 1 to 3 years, many irreversible serious ophthalmic and orbital complications can arise during this time. Therefore, there is a need for improved intervention strategies in the early active inflammatory phase of TED, to avoid progression to the cicatricial stage where disease manifestations can only be addressed in a rehabilitative fashion. The primary immunopathogenesis of Graves' disease is considered to be activation of B cells that then produce autoantibody against thyrotropin receptors in the thyroid (TRAb). Like in many autoimmune diseases, the inflammatory CD4+ T cell subset known as Th17 cells is also increased in blood of patients with active Graves' disease; the putative Th17 cytokine, IL-17, is also increased in serum and tears of TED patients. There is also an emerging pathogenic role for Th17 cells that co-express the chemokine receptor CXCR5 and drive autoantibody production. The contribution of Th17 cells to TED is not well defined. This study is an observational, longitudinal, prospective study of patients receiving treatment for thyroid eye disease.
All enrolled subjects will receive Intravenous Glucocorticoid (IVGC) therapy, which is currently the standard of care for TED patients. Subjects will receive the IVGC therapy at a facility chosen by them and their physician. If their disease does not respond to IVGC therapy, they will receive rituximab and/or surgical decompression and/or radiation which is also currently standard of care at a facility chosen by them and their physician. Prior to initiation of treatment and during the course of treatment, study patients will get research labs done along with routine labs and fill out questionnaires regarding their disease symptoms.
We will obtain 30 mL or 2 tablespoons of blood from subjects at initial evaluation and approximately Wk4, Wk 12, Wk 26, Wk 38, and Wk 52 (this may vary depending on when the patient comes in for their follow up visits, but the schedule approximates what is typical for standard of care in these patients) for mechanistic studies.
740 studies on the registry are indexed under Eye Diseases; 117 are open to participants now.
This study's enrollment of 2 is below the median of 120 across 172 observational studies indexed under Eye Diseases.
Browse Eye Diseases studies →University of Pittsburgh is the lead sponsor of 1,385 studies on the registry; 167 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 4 (50%) have results posted.
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The study will be introduced during a clinic visit with one of the physicians who are investigators on this study. These will be subjects who are being referred for intravenous glucocorticoid (IVGC) therapy due to the severe nature of their thyroid eye disease.
Exclusion Criteria:
Patients will be excluded from the study based on the following criteria:
Blood samples will be drawn from subjects diagnosed with Thyroid Eye Disease. This study is observational. No interventions will be given as part of this study.
Remission of disease activity (decrease in CAS of ≥ 2) at 26 weeks after first rituximab/placebo infusion
Remission of symptoms and disease activity by 26 weeks after the first dose of medication. Subjects will be followed for one year to assess relapse
Time frame: 26 weeks
Remission of disease activity (decrease in CAS of ≥ 2) at 6 and 14 weeks after first rituximab/placebo infusion.
Remission of symptoms by week 6 after treatment and again at week 14.
Time frame: 6 weeks
Maintenance of CAS (defined as no worsening of CAS or requirement of other interventions such as surgical decompression/orbital radiation by 26 weeks after first rituximab/placebo infusion .
Maintaining an absence of symptoms and disease activity.
Time frame: 26 weeks
Improvement in disease activity, as measured by CAS as a continuous variable at 6, 14, 26, 38 and 52 weeks after first infusion of rituximab,
Improvement in symptoms and disease activity
Time frame: 1 year
ll adverse effects related to RTX
Tracking any adverse events or serious adverse events related to rituximab.
Time frame: 1 year
Efficacy outcome as measured by Time to ≥ 2 points improvement on the CAS.
Time to ≥ 2 points improvement on the CAS.
Time frame: 1 year
Efficacy outcome as measured by Decrease in exophthalmos (measured in mm using the same Hertel exophthalmometer and same intercanthal distance for an individual patient).
Decrease in exophthalmos (measured in mm using the same Hertel exophthalmometer and same intercanthal distance for an individual patient).
Time frame: 1 year
Efficacy outcome
Decrease in lid aperture (distance between the lid margins in mm with patient looking in the primary position, sitting relaxed and with distant fixation).
Time frame: 1 year
Efficacy outcome as measured by Subjective diplopia score
Subjective diplopia score (0=no diplopia; 1=intermittent, i.e. diplopia in primary position of gaze, when tired or when first awakening; 2= inconstant, i.e. diplopia at extremes of gaze; 3=constant, i.e. continuous diplopia in primary or reading position).
Time frame: 1 year
Efficacy outcome as measured by Improvement in quality of life as measured by an SF-36 and GoQoL.
Improvement in quality of life as measured by an SF-36 and GoQoL.
Time frame: 1 year
Efficacy outcome as measured by Immunologic markers and mechanistic analyses to include studies of peripheral blood and thyroid B and T cells and autoantibody levels, thyroid volume, cellularity and function.
Immunologic markers and mechanistic analyses to include studies of peripheral blood and thyroid B and T cells and autoantibody levels, thyroid volume, cellularity and function.
Time frame: 1 year
This study is terminated, as verified in Nov 2019. You cannot join it, but the record below documents what was studied.
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