Back to resultsPrednisone Versus Doxycycline in the Treatment of Graves' Orbitopathy
Primary Purpose
Thyroid Associated Opthalmopathies
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Prednisone+placebo of Doxycycline
Doxycycline+placebo of Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Thyroid Associated Opthalmopathies
Eligibility 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
Sites / Locations
- Peking Union Medical College HospitalRecruiting
- Zhongshan Ophthalmic CenterRecruiting
- JOINT SHANTOU INTERNATIONALL EYE CENTER of Shantou University and the Chinese University of Hong KongRecruiting
- Shenzhen Eye HospitalRecruiting
- Henan Eye Institue, Henan, ChinaRecruiting
- The second xiangya hospital of central south universityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Prednisone+placebo of Doxycycline
Doxycycline+placebo of Prednisone
Arm Description
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.
Doxycycline: 50 mg/d for 12 weeks, and placebo for another 4 weeks; Placebo of prednisone: administered for 16 weeks.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
• 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
Full Information
NCT ID
NCT01809444
First Posted
December 2, 2012
Last Updated
December 7, 2013
Sponsor
Sun Yat-sen University
1. Study Identification
Unique Protocol Identification Number
NCT01809444
Brief Title
Prednisone Versus Doxycycline in the Treatment of Graves' Orbitopathy
Official Title
The Effect of Prednisone Versus Doxycycline in Active, Moderately Severe Graves' Orbitopathy: A Randomized, Multi-center, Double-blind, Parallel-controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Unknown status
Study Start Date
November 2012 (undefined)
Primary Completion Date
January 2016 (Anticipated)
Study Completion Date
January 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thyroid Associated Opthalmopathies
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
146 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Prednisone+placebo of Doxycycline
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Doxycycline+placebo of Prednisone
Arm Type
Experimental
Arm Description
Doxycycline: 50 mg/d for 12 weeks, and placebo for another 4 weeks; Placebo of prednisone: administered for 16 weeks.
Intervention Type
Drug
Intervention Name(s)
Prednisone+placebo of Doxycycline
Other Intervention Name(s)
deltacortisone
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Doxycycline+placebo of Prednisone
Other Intervention Name(s)
Dolotard, Tibirox, Biomycin
Intervention Description
Doxycycline: 50 mg PO per day for 12 weeks, and placebo for another 4 weeks; Placebo of prednisone: administered for 16 weeks.
Primary Outcome Measure Information:
Title
Overall treatment response
Description
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.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
• Health related quality of life questionnaires (GO-QoL)
Time Frame
24 weeks
Title
• Safety and tolerability as assessed by adverse events, vital signs
Time Frame
48 weeks
Title
• Quantitative changes of rectus diameter measured by MRI scan
Time Frame
24 weeks
Title
Relapse
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dan Liang, MD
Phone
0086-20-87331766
Email
liangd2@mail.sysu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Miaoli Lin, md
Phone
0086-20-87331537
Email
linml0754@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan Liang, MD
Organizational Affiliation
Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Liya Wang, MD
Organizational Affiliation
Henan Eye Institue, Henan, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Luosheng Tang, MD
Organizational Affiliation
The second xiangya hospital of central south university, Hunan, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yong Zhong, MD
Phone
+86-10-69156114
Email
yzhong_eye@yahoo.com.cn
Facility Name
Zhongshan Ophthalmic Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dan Liang, MD
Phone
0086-20-87331766
Email
liangd2@mail.sysu.edu.cn
Facility Name
JOINT SHANTOU INTERNATIONALL EYE CENTER of Shantou University and the Chinese University of Hong Kong
City
Shantou
State/Province
Guangdong
ZIP/Postal Code
515041
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mingzhi Zhang, MD
Phone
+86-754-88393501
Email
zmz@jsiec.org
Facility Name
Shenzhen Eye Hospital
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518040
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guiqin Liu, MD
Phone
+86-755-23959600
Email
liuguiqin9@yahoo.com.cn
Facility Name
Henan Eye Institue, Henan, China
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liya wang, MD
Phone
0086-13937169191
Email
wangliya55@126.com
Facility Name
The second xiangya hospital of central south university
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410011
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Xiong, MD
Phone
0086-138-0846-9035
Email
weixiong420@163.com
12. IPD Sharing Statement
Links:
URL
http://ghr.nlm.nih.gov/
Description
Genetics Home Reference related topics: Lenz microphthalmia syndrome oculofacioc
URL
http://www.nlm.nih.gov/medlineplus
Description
MedlinePlus related topics: Antibiotics Eye Diseases Thyroid Diseases
URL
http://www.clinicaltrials.gov/ct2/info/fdalinks
Description
U.S. FDA Resources
Learn more about this trial
Prednisone Versus Doxycycline in the Treatment of Graves' Orbitopathy
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