- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01809444
Prednisone Versus Doxycycline in the Treatment of Graves' Orbitopathy
The Effect of Prednisone Versus Doxycycline in Active, Moderately Severe Graves' Orbitopathy: A Randomized, Multi-center, Double-blind, Parallel-controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Miaoli Lin, md
- Phone Number: 0086-20-87331537
- Email: linml0754@gmail.com
Study Locations
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Beijing
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Beijing, Beijing, China, 100730
- Recruiting
- Peking Union Medical College Hospital
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Contact:
- Yong Zhong, MD
- Phone Number: +86-10-69156114
- Email: yzhong_eye@yahoo.com.cn
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Guangdong
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Guangzhou, Guangdong, China, 510060
- Recruiting
- Zhongshan Ophthalmic Center
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Shantou, Guangdong, China, 515041
- Recruiting
- JOINT SHANTOU INTERNATIONALL EYE CENTER of Shantou University and the Chinese University of Hong Kong
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Contact:
- Mingzhi Zhang, MD
- Phone Number: +86-754-88393501
- Email: zmz@jsiec.org
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Shenzhen, Guangdong, China, 518040
- Recruiting
- Shenzhen Eye Hospital
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Contact:
- Guiqin Liu, MD
- Phone Number: +86-755-23959600
- Email: liuguiqin9@yahoo.com.cn
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Henan
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Zhengzhou, Henan, China, 450003
- Recruiting
- Henan Eye Institue, Henan, China
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Contact:
- Liya wang, MD
- Phone Number: 0086-13937169191
- Email: wangliya55@126.com
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Hunan
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Changsha, Hunan, China, 410011
- Recruiting
- The second Xiangya Hospital of Central South University
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Contact:
- Wei Xiong, MD
- Phone Number: 0086-138-0846-9035
- Email: weixiong420@163.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Prednisone+placebo of Doxycycline
Prednisone: 50 mg/d for 14 day, tailed by 40 mg/d for 14 day, 30 mg/d for 28 day, 20 mg/d for 28 day, 15 mg/d for 14 day, 10 mg/d for 14 day, in total 16 weeks; Placebo of doxycycline: administered for 16 weeks.
|
Prednisone: 50 mg/d for 14 day, tailed by 40 mg/d for 14 day, 30 mg/d for 28 day, 20 mg/d for 28 day, 15 mg/d for 14 day, 10 mg/d for 14 day, in total 16 weeks; Placebo of doxycycline: administered for 16 weeks
Other Names:
|
EXPERIMENTAL: Doxycycline+placebo of Prednisone
Doxycycline: 50 mg/d for 12 weeks, and placebo for another 4 weeks; Placebo of prednisone: administered for 16 weeks.
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Doxycycline: 50 mg PO per day for 12 weeks, and placebo for another 4 weeks; Placebo of prednisone: administered for 16 weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall treatment response
Time Frame: 24 weeks
|
Overall treatment response was graded as: improvement, deterioration, and no success.
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
• Health related quality of life questionnaires (GO-QoL)
Time Frame: 24 weeks
|
24 weeks
|
• Safety and tolerability as assessed by adverse events, vital signs
Time Frame: 48 weeks
|
48 weeks
|
• Quantitative changes of rectus diameter measured by MRI scan
Time Frame: 24 weeks
|
24 weeks
|
Relapse
Time Frame: 48 weeks
|
48 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Liya Wang, MD, Henan Eye Institue, Henan, China
- Principal Investigator: Luosheng Tang, MD, The second xiangya hospital of central south university, Hunan, China
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Eye Diseases
- Endocrine System Diseases
- Genetic Diseases, Inborn
- Thyroid Diseases
- Eye Diseases, Hereditary
- Graves Disease
- Exophthalmos
- Orbital Diseases
- Goiter
- Hyperthyroidism
- Graves Ophthalmopathy
- Physiological Effects of Drugs
- Anti-Infective Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Anti-Bacterial Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Prednisone
- Doxycycline
Other Study ID Numbers
- 5010-doxy
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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