Celecoxib for Thyroid Eye Disease

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

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.

Study Overview

• Status: Terminated
• Conditions: Thyroid Eye Disease
• Intervention / Treatment: Drug: Celecoxib; Drug: artificial tears

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute, Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Celecoxib; 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; celecoxib 100mg PO twice per day for 3 months; Other Names: Celebrex; Drug: artificial tears; Standard care for mild thyroid eye disease is lubrication with artificial tears (over the counter), avoidance of cigarette smoke.
Active Comparator: Control; Patients who are randomized to standard treatment (requiring no prescription medication, but standard recommendations such as artificial tears, avoiding cigarette smoke)	Drug: artificial tears; Standard care for mild thyroid eye disease is lubrication with artificial tears (over the counter), avoidance of cigarette smoke.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Timothy J McCulley, MD, Wilmer Eye Institute, Johns Hopkins School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2017
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: July 20, 2016
• First Submitted That Met QC Criteria: July 22, 2016
• First Posted (Estimate): July 27, 2016

Study Record Updates

• Last Update Posted (Actual): July 31, 2020
• Last Update Submitted That Met QC Criteria: July 15, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Eye Diseases; Graves Ophthalmopathy; Thyroid Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Pharmaceutical Solutions; Ophthalmic Solutions; Celecoxib; Lubricant Eye Drops
• Other Study ID Numbers: IRB00094787

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes