Celecoxib for Thyroid Eye Disease

Study Overview
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Brief Summary
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Thyroid eye disease (TED) is an autoimmune disorder in which the immune system attacks orbital tissues, resulting in characteristic changes in eyelid position, globe position in the orbit, extraocular muscle balance, and optic nerve function. TED is a potentially blinding disease, and current treatments largely consist of nonspecific reduction of inflammation using corticosteroids or radiation therapy. Regardless of treatment, once TED progresses from its inflammatory phase to a more fibrotic, resolution phase, the orbital changes become fixed and can be modified only by surgery. The investigators propose to treat a cohort of patients with active TED using a selective COX-2 inhibitor, celecoxib, and to compare these patients to an observational control group. The investigators hypothesize that celecoxib will reduce the severity of disease and/or prevent progression to proptosis, diplopia, and corneal exposure or compressive optic neuropathy.

Detailed Description
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The investigators intend to use celecoxib, a non-steroidal anti-inflammatory drug approved by the Food and Drug Administration (FDA) for the treatment of pain, osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, as a treatment for active TED. In vitro data have shown that transformation of orbital fibroblasts into adipocytes is mediated by cyclooxygenase-2 (COX-2), and a case report suggests that COX-2 inhibition can improve TED in the acute phase. Thus, the investigators intend to evaluate the efficacy of COX-2 inhibition in the treatment of active TED and its ability to improve both the acute inflammatory signs and more permanent fibrotic changes of quiescent disease. The investigators will enroll patients with active TED and treat them for 3 months (a characteristic period of disease activity) and compare this to standard treatments for mild active TED (observation, with over the counter interventions such as lubrication with artificial tears) to assess efficacy.

Official Title
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An Open Label Trial of Celecoxib in the Treatment of Mild Thyroid Eye Disease

Conditions
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Thyroid Eye Disease

Intervention / Treatment
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* Drug: Celecoxib
* Drug: artificial tears


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recent diagnosis of thyroid eye disease (within the past 3 months) Have ocular symptoms or signs of TED with a clinical activity score (CAS) of at least 3 Exclusion Criteria: Pregnancy Previous treatment with corticosteroid for TED for >2wks Previous treatment with orbital radiation for TED Impaired renal function Impaired hepatic function Treatment with antihypertensive medications except beta-blockers History of congestive heart failure, cardiac valvular disease, or coronary artery disease Allergy to NSAID or previous adverse reaction (ie. GI bleeding) Vision loss due to compressive optic neuropathy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Celecoxib<br>Patients who are randomized to treatment with celecoxib 100mg pills by mouth twice a day for 3 months, in addition to standard of care treatment as described under the Control arm | Drug: Celecoxib<br>* celecoxib 100mg PO twice per day for 3 months<br>* Other names: Celebrex;Drug: artificial tears<br>* Standard care for mild thyroid eye disease is lubrication with artificial tears (over the counter), avoidance of cigarette smoke.<br>|
| Active Comparator: Control<br>Patients who are randomized to standard treatment (requiring no prescription medication, but standard recommendations such as artificial tears, avoiding cigarette smoke) | Drug: artificial tears<br>* Standard care for mild thyroid eye disease is lubrication with artificial tears (over the counter), avoidance of cigarette smoke.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thyroid Eye Disease Clinical Activity Score | A clinical score based on examination findings at each clinic visit. Clinical Activity Scores ranged from 0 to 10; 0 = Normal 1-3 = Mild 4-6 = Moderate 7-10 = Severe | At baseline, 1, 3 and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proptosis as Measured in Millimeters With an Exophthalmometer (Right Eye) | A clinical measure of how prominent the eyes are and any change in this measure over the duration of the study, as measured in millimeters with an exophthalmometer. | At baseline, 1, 3 and 6 months | 
| Proptosis as Measured in Millimeters With an Exophthalmometer (Left Eye) | A clinical measure of how prominent the eyes are and any change in this measure over the duration of the study, as measured in millimeters with an exophthalmometer. | At baseline, 1, 3 and 6 months | 
| Number of Participants With Ocular Misalignment | Presence or absence of ocular misalignment measured in prism diopters. | At baseline | 
| Number of Participants With Ocular Misalignment | Presence or absence of ocular misalignment measured in prism diopters. | At 1 month | 
| Number of Participants With Ocular Misalignment | Presence or absence of ocular misalignment measured in prism diopters. | At 3 months | 
| Number of Participants With Ocular Misalignment | Presence or absence of ocular misalignment measured in prism diopters. | At 6 months | 
| Eyelid Retraction as Measured in Millimeters (Right Eye) | A clinical measure of the most common manifestation of thyroid eye disease--change in eyelid retraction as measured in millimeters at each visit over the duration of the study. | At baseline, 1, 3 and 6 months | 
| Eyelid Retraction as Measured in Millimeters (Left Eye) | A clinical measure of the most common manifestation of thyroid eye disease--change in eyelid retraction as measured in millimeters at each visit over the duration of the study. | At baseline, 1, 3 and 6 months | 
| Quality of Life as Assessed by a Thyroid Eye Disease Specific Survey of Quality of Life | Thyroid eye disease specific survey of quality of life will be administered, and change in quality of life score over the duration of the study will be measured. | 6 months |