Hydroxychloroquine in Mild Graves' Orbitopathy
- Registration Number
- NCT05126147
- Lead Sponsor
- National Taiwan University Hospital
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 108
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Hydroxychloroquine Hydroxychloroquine Hydroxychloroquine 200mg twice daily for 6 months.
- Primary Outcome Measures
Name Time Method The change of ophthalmic outcome at 24 weeks and 48 weeks 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".
- Secondary Outcome Measures
Name Time Method The change of quality of life (GO-QoL) at 24 weeks and 48 weeks 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.
The change of muscle volume (cm^3) on computed tomography at 24 weeks and 48 weeks Change of muscle volume on noncontrast orbital CT
The change of fat volume (cm^3) on computed tomography at 24 weeks and 48 weeks Change of fat volume on noncontrast orbital CT
The change of orbital volume (cm^3) on computed tomography at 24 weeks and 48 weeks Change of orbital volume on noncontrast orbital CT
The change of muscle density on computed tomography at 24 weeks and 48 weeks The density of muscle is measured and recorded in Hounsfield units.
The change of fat density on computed tomography at 24 weeks and 48 weeks The density of fat is measured and recorded in Hounsfield units.
The change of diplopia score at 24 weeks and 48 weeks 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).
The change of clinical activity score (CAS) at 24 weeks and 48 weeks 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:
1. Spontaneous orbital pain
2. Gaze evoked orbital pain
3. Eyelid swelling that is considered to be due to active GO
4. Eyelid erythema
5. Conjunctival redness that is considered to be due to active GO
6. Chemosis
7. Inflammation of caruncle OR plicaThe change of visual acuity at 24 weeks and 48 weeks Evaluation of visual acuity will be done by the same ophthalmologist
The change of antithyroid peroxidase antibody (anti-TPO) (IU/mL) at 24 weeks and 48 weeks Change of thyroid autoantibodies
The change of thyroglobulin antibody (TA) (IU/mL) at 24 weeks and 48 weeks Change of thyroid autoantibodies
The change of thyrotropin-binding inhibiting immunoglobulin (TBII) (%). at 24 weeks and 48 weeks Change of thyroid autoantibodies
Trial Locations
- Locations (2)
National Taiwan University Hospital, Hsin-Chu branch
🇨🇳Hsinchu, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan