Celecoxib for Thyroid Eye Disease

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02845336

Enrollment

Registered

2016-07-27

Start date

2017-03-05

Completion date

2019-06-30

Last updated

2020-07-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Thyroid Eye Disease

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.

Interventions

DRUGCelecoxib

celecoxib 100mg PO twice per day for 3 months

DRUGartificial tears

Standard care for mild thyroid eye disease is lubrication with artificial tears (over the counter), avoidance of cigarette smoke.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Thyroid Eye Disease Clinical Activity Score	At baseline, 1, 3 and 6 months	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

Secondary

Measure	Time frame	Description
Proptosis as Measured in Millimeters With an Exophthalmometer (Left Eye)	At baseline, 1, 3 and 6 months	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.
Number of Participants With Ocular Misalignment	At baseline	Presence or absence of ocular misalignment measured in prism diopters.
Proptosis as Measured in Millimeters With an Exophthalmometer (Right Eye)	At baseline, 1, 3 and 6 months	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.
Eyelid Retraction as Measured in Millimeters (Left Eye)	At baseline, 1, 3 and 6 months	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.
Quality of Life as Assessed by a Thyroid Eye Disease Specific Survey of Quality of Life	6 months	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.
Eyelid Retraction as Measured in Millimeters (Right Eye)	At baseline, 1, 3 and 6 months	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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 Celecoxib: celecoxib 100mg PO twice per day for 3 months artificial tears: Standard care for mild thyroid eye disease is lubrication with artificial tears (over the counter), avoidance of cigarette smoke.	6
Control Patients who are randomized to standard treatment (requiring no prescription medication, but standard recommendations such as artificial tears, avoiding cigarette smoke) artificial tears: Standard care for mild thyroid eye disease is lubrication with artificial tears (over the counter), avoidance of cigarette smoke.	1
Total	7

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Inability to get medication	2	0
Overall Study	Lost to Follow-up	3	1

Baseline characteristics

Characteristic	Control	Total	Celecoxib
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	1 Participants	1 Participants
Age, Categorical Between 18 and 65 years	1 Participants	6 Participants	5 Participants
Race and Ethnicity Not Collected	—	0 Participants	—
Region of Enrollment United States	1 Participants	7 Participants	6 Participants
Sex: Female, Male Female	0 Participants	4 Participants	4 Participants
Sex: Female, Male Male	1 Participants	3 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 1	0 / 0
other Total, other adverse events	0 / 1	0 / 0
serious Total, serious adverse events	0 / 1	0 / 0

Outcome results

Primary

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

Time frame: At baseline, 1, 3 and 6 months