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Prednisone Versus Doxycycline in the Treatment of Graves' Orbitopathy
The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified December 2013 by Dan Liang, Sun Yat-sen University.
Recruitment status was: Recruiting
Recruitment status was: Recruiting
Sponsor:
Sun Yat-sen University
Information provided by (Responsible Party):
Dan Liang, Sun Yat-sen University
ClinicalTrials.gov Identifier:
NCT01809444
First received: December 2, 2012
Last updated: December 7, 2013
Last verified: December 2013
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Purpose
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).
| Condition | Intervention | Phase |
|---|---|---|
| Thyroid Associated Opthalmopathies | Drug: Prednisone+placebo of Doxycycline Drug: Doxycycline+placebo of Prednisone | Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | The Effect of Prednisone Versus Doxycycline in Active, Moderately Severe Graves' Orbitopathy: A Randomized, Multi-center, Double-blind, Parallel-controlled Trial |
Resource links provided by NLM:
MedlinePlus related topics:
Steroids
Drug Information available for:
Prednisone
Doxycycline
Doxycycline monohydrate
Doxycycline hyclate
Doxycycline calcium
U.S. FDA Resources
Further study details as provided by Dan Liang, Sun Yat-sen University:
Primary Outcome Measures:
- Overall treatment response [ Time Frame: 24 weeks ]
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.
Secondary Outcome Measures:
- • Health related quality of life questionnaires (GO-QoL) [ Time Frame: 24 weeks ]
- • Safety and tolerability as assessed by adverse events, vital signs [ Time Frame: 48 weeks ]
- • Quantitative changes of rectus diameter measured by MRI scan [ Time Frame: 24 weeks ]
- Relapse [ Time Frame: 48 weeks ]
| Estimated Enrollment: | 146 |
| Study Start Date: | November 2012 |
| Estimated Study Completion Date: | January 2016 |
| Estimated Primary Completion Date: | January 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
|
Drug: 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
Other Name: deltacortisone
|
|
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.
|
Drug: Doxycycline+placebo of Prednisone
Doxycycline: 50 mg PO per day for 12 weeks, and placebo for another 4 weeks; Placebo of prednisone: administered for 16 weeks.
Other Names:
|
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| Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01809444
Please refer to this study by its ClinicalTrials.gov identifier: NCT01809444
Contacts
| Contact: Dan Liang, MD | 0086-20-87331766 | liangd2@mail.sysu.edu.cn | |
| Contact: Miaoli Lin, md | 0086-20-87331537 | linml0754@gmail.com |
Locations
| China, Beijing | |
| Peking Union Medical College Hospital | Recruiting |
| Beijing, Beijing, China, 100730 | |
| Contact: Yong Zhong, MD +86-10-69156114 yzhong_eye@yahoo.com.cn | |
| China, Guangdong | |
| Zhongshan Ophthalmic Center | Recruiting |
| Guangzhou, Guangdong, China, 510060 | |
| Contact: Dan Liang, MD 0086-20-87331766 liangd2@mail.sysu.edu.cn | |
| JOINT SHANTOU INTERNATIONALL EYE CENTER of Shantou University and the Chinese University of Hong Kong | Recruiting |
| Shantou, Guangdong, China, 515041 | |
| Contact: Mingzhi Zhang, MD +86-754-88393501 zmz@jsiec.org | |
| Shenzhen Eye Hospital | Recruiting |
| Shenzhen, Guangdong, China, 518040 | |
| Contact: Guiqin Liu, MD +86-755-23959600 liuguiqin9@yahoo.com.cn | |
| China, Henan | |
| Henan Eye Institue, Henan, China | Recruiting |
| Zhengzhou, Henan, China, 450003 | |
| Contact: Liya wang, MD 0086-13937169191 wangliya55@126.com | |
| China, Hunan | |
| The second xiangya hospital of central south university | Recruiting |
| Changsha, Hunan, China, 410011 | |
| Contact: Wei Xiong, MD 0086-138-0846-9035 weixiong420@163.com | |
Sponsors and Collaborators
Sun Yat-sen University
Investigators
| Study Chair: | Dan Liang, MD | Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China |
| 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 |
More Information
Additional Information:
| Responsible Party: | Dan Liang, Zhongshan Ophthalmic Center, Sun Yat-sen University |
| ClinicalTrials.gov Identifier: | NCT01809444 History of Changes |
| Other Study ID Numbers: |
5010-doxy |
| Study First Received: | December 2, 2012 |
| Last Updated: | December 7, 2013 |
Additional relevant MeSH terms:
|
Graves Ophthalmopathy Graves Disease Eye Diseases, Hereditary Eye Diseases Exophthalmos Orbital Diseases Goiter Thyroid Diseases Endocrine System Diseases Hyperthyroidism Autoimmune Diseases Immune System Diseases Prednisone |
Doxycycline Anti-Inflammatory Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents Anti-Bacterial Agents Anti-Infective Agents Antimalarials Antiprotozoal Agents Antiparasitic Agents |
ClinicalTrials.gov processed this record on August 16, 2017