Graves OphthalmopathyPhase 4NCT05126147
Hydroxychloroquine in Mild Graves' Orbitopathy
A Phase 4 study testing Hydroxychloroquine in people with Graves Ophthalmopathy, run by National Taiwan University Hospital at 2 sites in Taiwan.
Trial summary
This study is aimed to investigate the effect of hydroxychloroquine in patients with mild Graves' orbitopathy (GO). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Graves Ophthalmopathy
- What is being tested?
- Hydroxychloroquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 2 sitesTaiwan
- Study dates
- 21 Mar 2022to 31 Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan2 sites, 2 recruiting
- Recruiting
National Taiwan University Hospital, Hsin-Chu branch
Hsinchu
Chia-Hung Lin, M.D., +886-3-6677600, chiahunglin@ntuh.gov.tw
- Recruiting
National Taiwan University Hospital
Taipei
Shyang-Rong Shih, +886-2-23123456, srshih@ntu.edu.tw
Hung-Yuan Li, +886-2-23123456, larsli@ntuh.gov.tw
About this study
Official title: 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).
Read the 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.
- Conditions
- Graves Ophthalmopathy
- Being tested
- Hydroxychloroquine
- Keywords
- Graves' ophthalmopathy, Graves' disease, Hydroxychloroquine, Orbital volumetry, GO-QoL questionnaire
- Medical subject headings
- Graves Ophthalmopathy, Graves Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Plaquenil
Compare the effects of hydroxychloroquine 200mg twice daily for 6 months with those without treatment.
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine | Experimental | Hydroxychloroquine 200mg twice daily for 6 months. Receives: Drug: Hydroxychloroquine |
| Control | No intervention | Observation and active surveillance. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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".
Measured: at 24 weeks and 48 weeks
Secondary outcomes (12)
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.
Measured: at 24 weeks and 48 weeks
The change of muscle volume (cm^3) on computed tomography
Change of muscle volume on noncontrast orbital CT
Measured: at 24 weeks and 48 weeks
The change of fat volume (cm^3) on computed tomography
Change of fat volume on noncontrast orbital CT
Measured: at 24 weeks and 48 weeks
The change of orbital volume (cm^3) on computed tomography
Change of orbital volume on noncontrast orbital CT
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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
Measured: at 24 weeks and 48 weeks
The change of visual acuity
Evaluation of visual acuity will be done by the same ophthalmologist
Measured: at 24 weeks and 48 weeks
The change of antithyroid peroxidase antibody (anti-TPO) (IU/mL)
Change of thyroid autoantibodies
Measured: at 24 weeks and 48 weeks
The change of thyroglobulin antibody (TA) (IU/mL)
Change of thyroid autoantibodies
Measured: at 24 weeks and 48 weeks
The change of thyrotropin-binding inhibiting immunoglobulin (TBII) (%).
Change of thyroid autoantibodies
Measured: at 24 weeks and 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2021
- Study start21 Mar 2022
- Primary completion30 Sep 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graves OphthalmopathyStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05126147
- Sponsor's protocol ID
- 202101055MINB
- Status last verified
- Jan 2025
- First submitted
- 5 Oct 2021
- Last updated
- 25 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) sharing is available upon request.
Publications
Lin CH, Wei YH, Lu JY, Li HY, Lee CW, Yang CY, Chang CH, Wu WC, Wang CY, Shih SR. A randomized controlled trial on the effect of hydroxychloroquine in mild Graves' orbitopathy (GO-HCQ): study protocol. Trials. 2025 Aug 4;26(1):272. doi: 10.1186/s13063-025-09002-6.
PubMed 40760017
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial on the Effect of Hydroxychloroquine in Mild Graves' Orbitopathy
- ClinicalTrials.gov ID
- NCT05126147
- Acronym / sponsor ID
- 202101055MINB
- Conditions
- Graves Ophthalmopathy
- Keywords
- Graves' ophthalmopathy, Graves' disease, Hydroxychloroquine, Orbital volumetry, GO-QoL questionnaire
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 21 Mar 2022 (actual)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 18 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine | Experimental | Drug: HydroxychloroquineHydroxychloroquine 200mg twice daily for 6 months. |
| Control | No intervention | –Observation and active surveillance. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxychloroquineAlso: PlaquenilCompare the effects of hydroxychloroquine 200mg twice daily for 6 months with those without treatment. | Drug | Hydroxychloroquine |
Primary outcome
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".
12 secondary outcomes
The change of quality of life (GO-QoL)
Time frame: at 24 weeks and 48 weeks
The change of muscle volume (cm^3) on computed tomography
Time frame: at 24 weeks and 48 weeks
The change of fat volume (cm^3) on computed tomography
Time frame: at 24 weeks and 48 weeks
The change of orbital volume (cm^3) on computed tomography
Time frame: at 24 weeks and 48 weeks
The change of muscle density on computed tomography
Time frame: at 24 weeks and 48 weeks
The change of fat density on computed tomography
Time frame: at 24 weeks and 48 weeks
The change of diplopia score
Time frame: at 24 weeks and 48 weeks
The change of clinical activity score (CAS)
Time frame: at 24 weeks and 48 weeks
The change of visual acuity
Time frame: at 24 weeks and 48 weeks
The change of antithyroid peroxidase antibody (anti-TPO) (IU/mL)
Time frame: at 24 weeks and 48 weeks
The change of thyroglobulin antibody (TA) (IU/mL)
Time frame: at 24 weeks and 48 weeks
The change of thyrotropin-binding inhibiting immunoglobulin (TBII) (%).
Time frame: at 24 weeks and 48 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2025.
- Derived from this study: PubMed 40760017Lin CH, Wei YH, Lu JY, Li HY, Lee CW, Yang CY, Chang CH, Wu WC, Wang CY, Shih SR. A randomized controlled trial on the effect of hydroxychloroquine in mild Graves' orbitopathy (GO-HCQ): study protocol. Trials. 2025 Aug 4;26(1):272. doi: 10.1186/s13063-025-09002-6.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) sharing is available upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydroxychloroquine in people with Graves Ophthalmopathy, run by National Taiwan University Hospital at 2 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shyang-Rong Shih (+886-2-23123456, srshih@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change of ophthalmic outcome (time frame: at 24 weeks and 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05126147, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2025.