Clinical trial NCT05126147: Hydroxychloroquine in Mild Graves' Orbitopathy
Official title: A Randomized Controlled Trial on the Effect of Hydroxychloroquine in Mild Graves' Orbitopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Graves Ophthalmopathy
Keywords: Graves' ophthalmopathy
Graves' disease
Hydroxychloroquine
Orbital volumetry
GO-QoL questionnaire
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2021-11-18
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: The change of ophthalmic outcome
timeFrame: at 24 weeks and 48 weeks
Secondary outcomes:
measure: The change of quality of life (GO-QoL)
timeFrame: at 24 weeks and 48 weeks
measure: The change of muscle volume (cm^3) on computed tomography
timeFrame: at 24 weeks and 48 weeks
measure: The change of fat volume (cm^3) on computed tomography
timeFrame: at 24 weeks and 48 weeks
measure: The change of orbital volume (cm^3) on computed tomography
timeFrame: at 24 weeks and 48 weeks
measure: The change of muscle density on computed tomography
timeFrame: at 24 weeks and 48 weeks
measure: The change of fat density on computed tomography
timeFrame: at 24 weeks and 48 weeks
measure: The change of diplopia score
timeFrame: at 24 weeks and 48 weeks
measure: The change of clinical activity score (CAS)
timeFrame: at 24 weeks and 48 weeks
measure: The change of visual acuity
timeFrame: at 24 weeks and 48 weeks
measure: The change of antithyroid peroxidase antibody (anti-TPO) (IU/mL)
timeFrame: at 24 weeks and 48 weeks
measure: The change of thyroglobulin antibody (TA) (IU/mL)
timeFrame: at 24 weeks and 48 weeks
measure: The change of thyrotropin-binding inhibiting immunoglobulin (TBII) (%).
timeFrame: at 24 weeks and 48 weeks
Other outcomes:
Locations:
city: Hsinchu
country: Taiwan
facility: National Taiwan University Hospital, Hsin-Chu branch
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References: