Prednisone Versus Doxycycline in the Treatment of Graves' Orbitopathy
|ClinicalTrials.gov Identifier: NCT01809444|
Recruitment Status : Unknown
Verified December 2013 by Dan Liang, Sun Yat-sen University.
Recruitment status was: Recruiting
First Posted : March 12, 2013
Last Update Posted : December 10, 2013
|Condition or disease||Intervention/treatment||Phase|
|Thyroid Associated Opthalmopathies||Drug: Prednisone+placebo of Doxycycline Drug: Doxycycline+placebo of Prednisone||Phase 2 Phase 3|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||146 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||The Effect of Prednisone Versus Doxycycline in Active, Moderately Severe Graves' Orbitopathy: A Randomized, Multi-center, Double-blind, Parallel-controlled Trial|
|Study Start Date :||November 2012|
|Estimated Primary Completion Date :||January 2016|
|Estimated Study Completion Date :||January 2016|
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.
- 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.
- • 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01809444
|Contact: Dan Liang, MDfirstname.lastname@example.org|
|Contact: Miaoli Lin, email@example.com|
|Peking Union Medical College Hospital||Recruiting|
|Beijing, Beijing, China, 100730|
|Contact: Yong Zhong, MD +86-10-69156114 firstname.lastname@example.org|
|Zhongshan Ophthalmic Center||Recruiting|
|Guangzhou, Guangdong, China, 510060|
|Contact: Dan Liang, MD 0086-20-87331766 email@example.com|
|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 firstname.lastname@example.org|
|Shenzhen Eye Hospital||Recruiting|
|Shenzhen, Guangdong, China, 518040|
|Contact: Guiqin Liu, MD +86-755-23959600 email@example.com|
|Henan Eye Institue, Henan, China||Recruiting|
|Zhengzhou, Henan, China, 450003|
|Contact: Liya wang, MD 0086-13937169191 firstname.lastname@example.org|
|The second xiangya hospital of central south university||Recruiting|
|Changsha, Hunan, China, 410011|
|Contact: Wei Xiong, MD 0086-138-0846-9035 email@example.com|
|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|