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NCT Number: NCT05126147

Hydroxychloroquine in Mild Graves' Orbitopathy

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

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Key information

Conditions

Graves Ophthalmopathy Autoimmune Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Endocrine System Diseases Exophthalmos Eye Diseases Eye Diseases, Hereditary Genetic Diseases, Inborn Goiter Graves Disease Hyperthyroidism Immune System Diseases Orbital Diseases Thyroid Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

National Taiwan University Hospital, Hsin-Chu branch, Hsinchu, Taiwan

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Hydroxychloroquine

Drug

Compare the effects of hydroxychloroquine 200mg twice daily for 6 months with those without treatment.

Other names: Plaquenil

Primary outcomes

  1. The change of ophthalmic outcome

    Time frame: 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 outcomes

  1. The change of quality of life (GO-QoL)

    Time frame: 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.

  2. The change of muscle volume (cm^3) on computed tomography

    Time frame: at 24 weeks and 48 weeks

    Change of muscle volume on noncontrast orbital CT

  3. The change of fat volume (cm^3) on computed tomography

    Time frame: at 24 weeks and 48 weeks

    Change of fat volume on noncontrast orbital CT

  4. The change of orbital volume (cm^3) on computed tomography

    Time frame: at 24 weeks and 48 weeks

    Change of orbital volume on noncontrast orbital CT

  5. The change of muscle density on computed tomography

    Time frame: at 24 weeks and 48 weeks

    The density of muscle is measured and recorded in Hounsfield units.

  6. The change of fat density on computed tomography

    Time frame: at 24 weeks and 48 weeks

    The density of fat is measured and recorded in Hounsfield units.

  7. The change of diplopia score

    Time frame: 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).

  8. The change of clinical activity score (CAS)

    Time frame: 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:

    • 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

  9. The change of visual acuity

    Time frame: at 24 weeks and 48 weeks

    Evaluation of visual acuity will be done by the same ophthalmologist

  10. The change of antithyroid peroxidase antibody (anti-TPO) (IU/mL)

    Time frame: at 24 weeks and 48 weeks

    Change of thyroid autoantibodies

  11. The change of thyroglobulin antibody (TA) (IU/mL)

    Time frame: at 24 weeks and 48 weeks

    Change of thyroid autoantibodies

  12. The change of thyrotropin-binding inhibiting immunoglobulin (TBII) (%).

    Time frame: at 24 weeks and 48 weeks

    Change of thyroid autoantibodies

Study contacts

Contact information is provided by the study sponsor or research team.

Hung-Yuan Li

CONTACT

[email protected]

+886-2-23123456

Shyang-Rong Shih

CONTACT

[email protected]

+886-2-23123456

Sponsors and collaborators

Lead sponsor

National Taiwan University Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2025
Study completion
2026
First posted
Nov 18, 2021
Registry last updated
Feb 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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