Hydroxychloroquine in Mild Graves' Orbitopathy

A Randomized Controlled Trial on the Effect of Hydroxychloroquine in Mild Graves' Orbitopathy

This study is aimed to investigate the effect of hydroxychloroquine in patients with mild Graves' orbitopathy (GO).

Study Overview

• Status: Recruiting
• Conditions: Graves Ophthalmopathy
• Intervention / Treatment: Drug: Hydroxychloroquine

Detailed Description

Graves' orbitopathy (GO) is one of the common manifestations of Graves' disease (GD), which results in proptosis, eyelid retraction, soft tissue swelling, diplopia or even visual acuity impairment. In addition, mental health and quality of life are often affected. In current guidelines, limited treatment options are suggested for patients with mild GO.

Recently, cell study revealed that there are multiple effects of hydroxychloroquine (HCQ) on orbital fibroblasts in patients with mild GO, including suppression of cell proliferation, adipogenesis and production of hyaluronic acid, which poses a great potential in the treatment of mild GO clinically. This randomized controlled trial is aimed to investigate the effects of HCQ in patients with mild GO on the effects of ophthalmic outcomes, quality of life, orbital volumetry on orbital computed tomography, serum inflammatory and fibrosis markers.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Shyang-Rong Shih; Phone Number: +886-2-23123456; Email: srshih@ntu.edu.tw
• Study Contact Backup: Name: Hung-Yuan Li; Phone Number: +886-2-23123456; Email: larsli@ntuh.gov.tw

Study Locations

• Taiwan
  • Hsinchu, Taiwan
    • Recruiting
    • National Taiwan University Hospital, Hsin-Chu Branch
    • Contact: Chia-Hung Lin, M.D.; Phone Number: +886-3-6677600; Email: chiahunglin@ntuh.gov.tw
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Shyang-Rong Shih; Phone Number: +886-2-23123456; Email: srshih@ntu.edu.tw
    • Contact: Hung-Yuan Li; Phone Number: +886-2-23123456; Email: larsli@ntuh.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Mild GO according European Group on Graves' orbitopathy (EUGOGO) guidelines diagnosed by endocrinologist and ophthalmologist.
• No previous treatment of GO except for eyedrops
• Euthyroidism (normalized free T4 and TSH) for at least 2 months. If radioactive iodine is used for hyperthyroidism, euthyroidism needs to be achieved for at least 6 months.

Exclusion Criteria:

• Moderate-to-sever or sight-threatening GO according to EUGOGO guidelines diagnosed by endocrinologist and ophthalmologist.
• Pregnancy
• Drug or alcohol abuse
• Unable to comply with the study protocol
• Unable to obtain informed consent
• Use of hydroxychloroquine or systemic steroid within 3 months prior to enrollment
• History of side effects of hydroxychloroquine
• History of retinopathy
• Renal dysfunction (estimated glomerular filtration rate (eGFR) < 60ml/min)
• Hepatic dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x upper limit)
• Anemia (hemoglobin (Hb) < 10g/dl)
• Neutropenia (absolute neutrophil count < 100/uL)
• Thrombocytopenia (platelet (PLT) < 150000/uL)
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Porphyria cutaneous tarda
• Allergy to 4-aminoquinoline

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: Hydroxychloroquine; Hydroxychloroquine 200mg twice daily for 6 months.	Drug: Hydroxychloroquine; Compare the effects of hydroxychloroquine 200mg twice daily for 6 months with those without treatment.; Other Names: Plaquenil
No Intervention: Control; Observation and active surveillance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of ophthalmic outcome	The ophthalmic outcome is a composite outcome which includes three components: eyelid aperture, soft tissue involvement and exophthalmos. The outcome is defined as "improvement" if any of the three components improves without deterioration of any other components. The outcome of "deterioration" is defined if upgrading of soft tissue involvement or evidence of worsening sight or optic nerve compression. The outcome of "stable" is defined if the ophthalmic outcome does not fit the definition of "improvement" or "deterioration".	at 24 weeks and 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of quality of life (GO-QoL)	The outcome is grading as improvement, stable and deterioration. Improvement is defined if there are more than 6 points increase in any of the category in GO-QoL. Deterioration is defined if there are more than 6 points decrease in any of the category in GO-QoL. Stable is defined if none of above criteria is achieved.	at 24 weeks and 48 weeks
The change of muscle volume (cm^3) on computed tomography	Change of muscle volume on noncontrast orbital CT	at 24 weeks and 48 weeks
The change of fat volume (cm^3) on computed tomography	Change of fat volume on noncontrast orbital CT	at 24 weeks and 48 weeks
The change of orbital volume (cm^3) on computed tomography	Change of orbital volume on noncontrast orbital CT	at 24 weeks and 48 weeks
The change of muscle density on computed tomography	The density of muscle is measured and recorded in Hounsfield units.	at 24 weeks and 48 weeks
The change of fat density on computed tomography	The density of fat is measured and recorded in Hounsfield units.	at 24 weeks and 48 weeks
The change of diplopia score	The Gorman diplopia score includes four categories: no diplopia(absent), diplopia when the patient is tired or awakening (intermittent), diplopia at extremes of gaze (inconstant), and continuous diplopia in the primary or reading position (constant).	at 24 weeks and 48 weeks
The change of clinical activity score (CAS)	Clinical activity score (CAS) is a 7-point scale using to evaluate the activity of GO in each eye. It includes 7 items to be scored respectively in each eye with minimum 0 point and maximum 7 points. More points indicate that GO in the eye is more active. The 7 items are listed as below: Spontaneous orbital pain; Gaze evoked orbital pain; Eyelid swelling that is considered to be due to active GO; Eyelid erythema; Conjunctival redness that is considered to be due to active GO; Chemosis; Inflammation of caruncle OR plica	at 24 weeks and 48 weeks
The change of visual acuity	Evaluation of visual acuity will be done by the same ophthalmologist	at 24 weeks and 48 weeks
The change of antithyroid peroxidase antibody (anti-TPO) (IU/mL)	Change of thyroid autoantibodies	at 24 weeks and 48 weeks
The change of thyroglobulin antibody (TA) (IU/mL)	Change of thyroid autoantibodies	at 24 weeks and 48 weeks
The change of thyrotropin-binding inhibiting immunoglobulin (TBII) (%).	Change of thyroid autoantibodies	at 24 weeks and 48 weeks

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2022
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 5, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): November 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 23, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Hydroxychloroquine; Graves' disease; Graves' ophthalmopathy; Orbital volumetry; GO-QoL questionnaire
• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Autoimmune Diseases; Immune System Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Eye Diseases; Graves Ophthalmopathy; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Hydroxychloroquine
• Other Study ID Numbers: 202101055MINB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) sharing is available upon request.
• IPD Sharing Time Frame: Data will become available after completed study enrollment.
• IPD Sharing Access Criteria: Individual participant data (IPD) sharing is available upon request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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