Thyroid Associated Opthalmopathies Clinical Trial
Official title:
The Effect of Prednisone Versus Doxycycline in Active, Moderately Severe Graves' Orbitopathy: A Randomized, Multi-center, Double-blind, Parallel-controlled Trial
The aim of this study is to compare the efficacy and safety of prednisone versus sub-antimicrobial dose doxycycline (50 mg/d) in the treatment of active moderate-severe Graves' Orbitopathy (GO).
| Status | Recruiting |
| Enrollment | 146 |
| Est. completion date | January 2016 |
| Est. primary completion date | January 2016 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 60 Years |
| Eligibility |
Inclusion Criteria: - Confirmed diagnosis of Graves' Orbitopathy (as defined by Bartley and Gorman) - Eyelid retraction (upper eyelid margin at or above the superior corneoscleral limbus in primary gaze without frontalis muscle contraction) in association with any one of the following: - Thyroid dysfunction or abnormal regulation (increased serum thyroxine or triiodothyronine level, decreased serum thyroid stimulating hormone level, absence of thyroid radioiodine uptake suppression after administration of triiodothyronine, or the presence of thyroid stimulating immunoglobulins in serum) - Exophthalmos - Extraocular muscle involvement (restrictive myopathy or objective evidence of enlarged muscles) - Optic nerve dysfunction (abnormal visual acuity, color vision, pupillary reaction or perimetry not attributable to other causes) OR - Thyroid dysfunction or abnormal regulation in association with any one of the following: - Exophthalmos - Extraocular muscle involvement - Optic nerve dysfunction - Moderate-severe GO According to EUGOGO statement, patients with moderate-severe GO usually have any one or more of the following:lid retraction=2mm, moderate or severe soft tissue involvement, exophthalmos=3mm above normal for race and gender, inconstant, or constant diplopia. - Clinical activity score = 3 - Being euthyroid for at least 1 months before the date of inclusion - Must be able to swallow tablets - Written informed consent is obtained Exclusion Criteria: - Mild Graves' Orbitopathy - Sight-threatening Graves' Orbitopathy - Clinical activity score < 3 - Previous treatment for GO Oral steroids, intravenous steroids, radiotherapy - Pregnant females as determined by positive (serum or urine) human chorionic gonadotrophin (hCG) test at screening or prior to dosing, or lactating females - Uncontrolled diabetes or hypertension - History of mental / psychiatric disorder - Hepatic dysfunction (Albumin (Alb) , Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline phosphates levels must be within normal range for eligibility) - Renal impairment (Urea and Creatinine levels must be within normal range) - Doxycycline or Prednisone allergy or intolerance |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| China | Peking Union Medical College Hospital | Beijing | Beijing |
| China | The second xiangya hospital of central south university | Changsha | Hunan |
| China | Zhongshan Ophthalmic Center | Guangzhou | Guangdong |
| China | JOINT SHANTOU INTERNATIONALL EYE CENTER of Shantou University and the Chinese University of Hong Kong | Shantou | Guangdong |
| China | Shenzhen Eye Hospital | Shenzhen | Guangdong |
| China | Henan Eye Institue, Henan, China | Zhengzhou | Henan |
| Lead Sponsor | Collaborator |
|---|---|
| Sun Yat-sen University |
China,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall treatment response | Overall treatment response was graded as: improvement, deterioration, and no success. Improvement, when at least one major criteria or two minor criteria were achieved, in absence of deterioration of any criterion in that observed eye.Three major criteria were: improvement in diplopia grade (disappearance or change in grade); improvement of =8 degrees in any direction of eye movements; reduction of three points or more in CAS. Four minor criteria were: reduction of 2 mm or more in eyelid aperture; reduction of 2 mm or more in proptosis; improvement in grade of soft tissue swelling; decrease in CAS by at least two points. Deterioration, defined as occurrence of DON, and/or worsening of soft tissue swelling, and/or worsening of diplopia, and/or an increase of =2 mm in lid aperture, and/or an increase of =2 mm in proptosis, and/or a decrease of =8 degrees in duction. No success was defined if there was no change or the changes did not reach the improvement criteria. |
24 weeks | No |
| Secondary | • Health related quality of life questionnaires (GO-QoL) | 24 weeks | No | |
| Secondary | • Safety and tolerability as assessed by adverse events, vital signs | 48 weeks | Yes | |
| Secondary | • Quantitative changes of rectus diameter measured by MRI scan | 24 weeks | No | |
| Secondary | Relapse | 48 weeks | No |