Clinical trial NCT02845336: Celecoxib for Thyroid Eye Disease
Official title: An Open Label Trial of Celecoxib in the Treatment of Mild Thyroid Eye Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Thyroid Eye Disease
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2016-07-27
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Thyroid Eye Disease Clinical Activity Score
timeFrame: At baseline, 1, 3 and 6 months
Secondary outcomes:
measure: Proptosis as Measured in Millimeters With an Exophthalmometer (Right Eye)
timeFrame: At baseline, 1, 3 and 6 months
measure: Proptosis as Measured in Millimeters With an Exophthalmometer (Left Eye)
timeFrame: At baseline, 1, 3 and 6 months
measure: Number of Participants With Ocular Misalignment
timeFrame: At baseline
measure: Number of Participants With Ocular Misalignment
timeFrame: At 1 month
measure: Number of Participants With Ocular Misalignment
timeFrame: At 3 months
measure: Number of Participants With Ocular Misalignment
timeFrame: At 6 months
measure: Eyelid Retraction as Measured in Millimeters (Right Eye)
timeFrame: At baseline, 1, 3 and 6 months
measure: Eyelid Retraction as Measured in Millimeters (Left Eye)
timeFrame: At baseline, 1, 3 and 6 months
measure: Quality of Life as Assessed by a Thyroid Eye Disease Specific Survey of Quality of Life
timeFrame: 6 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Wilmer Eye Institute, Johns Hopkins University
state: Maryland
Study officials:
affiliation: Wilmer Eye Institute, Johns Hopkins School of Medicine
name: Timothy J McCulley, MD
role: PRINCIPAL_INVESTIGATOR
References: