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Hydroxychloroquine in Mild Graves' Orbitopathy

Primary Purpose

Graves Ophthalmopathy

Status
Recruiting
Phase
Phase 4
Locations
Taiwan
Study Type
Interventional
Intervention
Hydroxychloroquine
Sponsored by
National Taiwan University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graves Ophthalmopathy focused on measuring Graves' ophthalmopathy, Graves' disease, Hydroxychloroquine, Orbital volumetry, GO-QoL questionnaire

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Mild or moderate-to-severe GO according European Group on Graves' orbitopathy (EUGOGO) guidelines diagnosed by endocrinologist and ophthalmologist. Three categories of participants are included:

    1. Mild GO
    2. Active moderate-to-severe GO with contraindication to glucocorticoid
    3. Inactive moderate-to-severe GO
  • 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:

  • 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

Sites / Locations

  • National Taiwan University Hospital, Hsin-Chu branchRecruiting
  • National Taiwan University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Hydroxychloroquine

Control

Arm Description

Hydroxychloroquine 200mg twice daily for 6 months.

Observation and active surveillance.

Outcomes

Primary Outcome Measures

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".

Secondary Outcome Measures

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.
The change of muscle volume (cm^3) on computed tomography
Change of muscle volume on noncontrast orbital CT
The change of fat volume (cm^3) on computed tomography
Change of fat volume on noncontrast orbital CT
The change of orbital volume (cm^3) on computed tomography
Change of orbital volume on noncontrast orbital CT
The change of muscle density on computed tomography
The density of muscle is measured and recorded in Hounsfield units.
The change of fat density on computed tomography
The density of fat is measured and recorded in Hounsfield units.
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).
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
The change of visual acuity
Evaluation of visual acuity will be done by the same ophthalmologist
The change of antithyroid peroxidase antibody (anti-TPO) (IU/mL)
Change of thyroid autoantibodies
The change of thyroglobulin antibody (TA) (IU/mL)
Change of thyroid autoantibodies
The change of thyrotropin-binding inhibiting immunoglobulin (TBII) (%).
Change of thyroid autoantibodies

Full Information

First Posted
October 5, 2021
Last Updated
December 1, 2022
Sponsor
National Taiwan University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05126147
Brief Title
Hydroxychloroquine in Mild Graves' Orbitopathy
Official Title
A Randomized Controlled Trial on the Effect of Hydroxychloroquine in Mild Graves' Orbitopathy
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2022 (Actual)
Primary Completion Date
March 21, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graves Ophthalmopathy
Keywords
Graves' ophthalmopathy, Graves' disease, Hydroxychloroquine, Orbital volumetry, GO-QoL questionnaire

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
108 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hydroxychloroquine
Arm Type
Experimental
Arm Description
Hydroxychloroquine 200mg twice daily for 6 months.
Arm Title
Control
Arm Type
No Intervention
Arm Description
Observation and active surveillance.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Other Intervention Name(s)
Plaquenil
Intervention Description
Compare the effects of hydroxychloroquine 200mg twice daily for 6 months with those without treatment.
Primary Outcome Measure Information:
Title
The change of ophthalmic outcome
Description
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".
Time Frame
at 24 weeks and 48 weeks
Secondary Outcome Measure Information:
Title
The change of quality of life (GO-QoL)
Description
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.
Time Frame
at 24 weeks and 48 weeks
Title
The change of muscle volume (cm^3) on computed tomography
Description
Change of muscle volume on noncontrast orbital CT
Time Frame
at 24 weeks and 48 weeks
Title
The change of fat volume (cm^3) on computed tomography
Description
Change of fat volume on noncontrast orbital CT
Time Frame
at 24 weeks and 48 weeks
Title
The change of orbital volume (cm^3) on computed tomography
Description
Change of orbital volume on noncontrast orbital CT
Time Frame
at 24 weeks and 48 weeks
Title
The change of muscle density on computed tomography
Description
The density of muscle is measured and recorded in Hounsfield units.
Time Frame
at 24 weeks and 48 weeks
Title
The change of fat density on computed tomography
Description
The density of fat is measured and recorded in Hounsfield units.
Time Frame
at 24 weeks and 48 weeks
Title
The change of diplopia score
Description
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).
Time Frame
at 24 weeks and 48 weeks
Title
The change of clinical activity score (CAS)
Description
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
Time Frame
at 24 weeks and 48 weeks
Title
The change of visual acuity
Description
Evaluation of visual acuity will be done by the same ophthalmologist
Time Frame
at 24 weeks and 48 weeks
Title
The change of antithyroid peroxidase antibody (anti-TPO) (IU/mL)
Description
Change of thyroid autoantibodies
Time Frame
at 24 weeks and 48 weeks
Title
The change of thyroglobulin antibody (TA) (IU/mL)
Description
Change of thyroid autoantibodies
Time Frame
at 24 weeks and 48 weeks
Title
The change of thyrotropin-binding inhibiting immunoglobulin (TBII) (%).
Description
Change of thyroid autoantibodies
Time Frame
at 24 weeks and 48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shyang-Rong Shih
Phone
+886-2-23123456
Email
srshih@ntu.edu.tw
First Name & Middle Initial & Last Name or Official Title & Degree
Hung-Yuan Li
Phone
+886-2-23123456
Email
larsli@ntuh.gov.tw
Facility Information:
Facility Name
National Taiwan University Hospital, Hsin-Chu branch
City
Hsinchu
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chia-Hung Lin, M.D.
Phone
+886-3-6677600
Email
G02299@hch.gov.tw
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shyang-Rong Shih
Phone
+886-2-23123456
Email
srshih@ntu.edu.tw
First Name & Middle Initial & Last Name & Degree
Hung-Yuan Li
Phone
+886-2-23123456
Email
larsli@ntuh.gov.tw

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data (IPD) sharing is available upon request.
IPD Sharing Time Frame
Data will become available after completed study enrollment.
IPD Sharing Access Criteria
Individual participant data (IPD) sharing is available upon request.

Learn more about this trial

Hydroxychloroquine in Mild Graves' Orbitopathy

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