A randomized controlled trial on the effect of hydroxychloroquine in mild Graves’ orbitopathy (GO-HCQ): study protocol

TL;DR

This study will test if hydroxychloroquine helps treat mild Graves’ orbitopathy by measuring eye-related outcomes and quality of life in patients.

Contribution

This is the first randomized controlled trial to evaluate hydroxychloroquine's efficacy in mild Graves’ orbitopathy.

Findings

The trial will assess ophthalmic parameters like eyelid aperture and exophthalmos as primary outcomes.

Orbital CT scans will provide objective data on changes in fat and muscle volumes.

Quality of life and disease activity will be evaluated as secondary endpoints.

Abstract

Graves’ orbitopathy (GO) is a prevalent manifestation of Graves’ disease (GD), characterized by proptosis, eyelid retraction, soft tissue swelling, diplopia, and potential visual acuity impairment. Furthermore, even mild GO can significantly impact mental health and overall quality of life for patients with GD. Despite its severity, available medical treatments for mild GO are limited. Recent basic studies on orbital fibroblasts suggest hydroxychloroquine (HCQ) as a promising therapeutic agent for GO patients. This randomized controlled trial (RCT) was designed to assess the efficacy of HCQ in treating mild GO.

This multi-center open-label RCT will be conducted in Taiwan with a total of 108 participants randomized into HCQ and control groups at 2:1 allocation ratio. The primary endpoint of this study is a composite outcome of ophthalmic parameters including eyelid aperture, soft tissue involvement, and exophthalmos. Secondary endpoints comprise changes in quality of life (GO-QoL), orbital volumetry via computed tomography (CT), diplopia scores, clinical activity scores (CAS), visual acuity, and thyroid autoantibodies.

This RCT will elucidate the clinical benefits of oral HCQ in patients with mild GO, assessing ophthalmic outcomes, quality of life, disease activity, and thyroid autoantibodies. In addition, data obtained from orbital CT measurements will provide valuable insights into subtle changes in orbital fat and extra-ocular muscle volumes, potentially offering an objective tool for monitoring GO progression.

ClinicalTrials.gov NCT05126147. Registered on November 2021. https://clinicaltrials.gov/study/NCT05126147. All items from the World Health Organization (WHO) Trial Registration Data Set are addressed within the relevant sections of this protocol.

The online version contains supplementary material available at 10.1186/s13063-025-09002-6.

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