Prednisone Versus Doxycycline in the Treatment of Graves' Orbitopathy
Information source: Sun Yat-sen University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Thyroid Associated Opthalmopathies
Intervention: Prednisone+placebo of Doxycycline (Drug); Doxycycline+placebo of Prednisone (Drug)
Phase: Phase 2/Phase 3
Status: Recruiting
Sponsored by: Sun Yat-sen University Official(s) and/or principal investigator(s): Dan Liang, MD, Study Chair, Affiliation: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China Liya Wang, MD, Principal Investigator, Affiliation: Henan Eye Institue, Henan, China Luosheng Tang, MD, Principal Investigator, Affiliation: The second xiangya hospital of central south university, Hunan, China
Overall contact: Dan Liang, MD, Phone: 0086-20-87331766, Email: liangd2@mail.sysu.edu.cn
Summary
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).
Clinical Details
Official title: The Effect of Prednisone Versus Doxycycline in Active, Moderately Severe Graves' Orbitopathy: A Randomized, Multi-center, Double-blind, Parallel-controlled Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Overall treatment response
Secondary outcome: • Health related quality of life questionnaires (GO-QoL)• Safety and tolerability as assessed by adverse events, vital signs • Quantitative changes of rectus diameter measured by MRI scan Relapse
Detailed description:
Graves' orbitopathy is an autoimmune disease characterized by an inflammatory phase followed
by fibrosis. Surgery to correct eyelid swelling, proptosis, and diplopia is effective, but
can not be done until the inflammatory phase has passed. To arrest the inflammatory phase,
several types of immunosuppressive treatments have been investigated. Corticosteroids are
the first-choice immunosuppressive treatment, having a successful outcome of 50-70% in
patients. However, long time usage of corticosteroids often cause severe side-effects.
Sub-antimicrobial dose doxycycline posses known anti-inflammatory effects that are separate
from their antibacterial mode of action. This mode of action has lead to the routine use of
sub-antimicrobial dose doxycycline for treating inflammatory or autoimmune diseases, such as
rosacea, periodontitis and multiple sclerosis. The mechanism is by inhibiting lymphocyte
proliferation and production of colony-stimulating factor, inflammatory cytokines, and
immunoglobulins, factors thought to play a role in the orbital autoimmune process. These
mechanisms make them, in theory, an attractive option of doxycycline for treating Graves'
Orbitopathy. In addition, only few adverse events were reported when doxycycline were
administered for 3 months in patients with periodontitis or rosacea.
We propose to compare the effect and safety of sub-antimicrobial dose doxycycline versus
prednisone for treating non-sight threatening, moderate-severe, inflammatory GO.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Dan Liang, MD, Phone: 0086-20-87331766, Email: liangd2@mail.sysu.edu.cn
Peking Union Medical College Hospital, Beijing, Beijing 100730, China; Recruiting Yong Zhong, MD, Phone: +86-10-69156114, Email: yzhong_eye@yahoo.com.cn
Zhongshan Ophthalmic Center, Guangzhou, Guangdong 510060, China; Recruiting Dan Liang, MD, Phone: 0086-20-87331766, Email: liangd2@mail.sysu.edu.cn
JOINT SHANTOU INTERNATIONALL EYE CENTER of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong 515041, China; Recruiting Mingzhi Zhang, MD, Phone: +86-754-88393501, Email: zmz@jsiec.org
Shenzhen Eye Hospital, Shenzhen, Guangdong 518040, China; Recruiting Guiqin Liu, MD, Phone: +86-755-23959600, Email: liuguiqin9@yahoo.com.cn
Henan Eye Institue, Henan, China, Zhengzhou, Henan 450003, China; Recruiting Liya wang, MD, Phone: 0086-13937169191, Email: wangliya55@126.com
The second xiangya hospital of central south university, Changsha, Hunan 410011, China; Recruiting Wei Xiong, MD, Phone: 0086-138-0846-9035, Email: weixiong420@163.com
Additional Information
Genetics Home Reference related topics: Lenz microphthalmia syndrome oculofacioc MedlinePlus related topics: Antibiotics Eye Diseases Thyroid Diseases U.S. FDA Resources
Starting date: November 2012
Last updated: December 7, 2013
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