Thyroid Associated OpthalmopathiesPhase 2/3NCT01809444
Prednisone Versus Doxycycline in the Treatment of Graves' Orbitopathy
A Phase 2/3 study of Thyroid Associated Opthalmopathies, run by Sun Yat-sen University at 6 sites in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Thyroid Associated Opthalmopathies
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 146 participants
- Where
- 6 sitesChina
- Study dates
- Nov 2012to Jan 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
China6 sites, 6 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Yong Zhong, MD, +86-10-69156114, yzhong_eye@yahoo.com.cn
- Recruiting
The second xiangya hospital of central south university
Changsha, Hunan, 410011
Wei Xiong, MD, 0086-138-0846-9035, weixiong420@163.com
- Recruiting
Zhongshan Ophthalmic Center
Guangzhou, Guangdong, 510060
Dan Liang, MD, 0086-20-87331766, liangd2@mail.sysu.edu.cn
- Recruiting
JOINT SHANTOU INTERNATIONALL EYE CENTER of Shantou University and the Chinese University of Hong Kong
Shantou, Guangdong, 515041
Mingzhi Zhang, MD, +86-754-88393501, zmz@jsiec.org
- Recruiting
Shenzhen Eye Hospital
Shenzhen, Guangdong, 518040
Guiqin Liu, MD, +86-755-23959600, liuguiqin9@yahoo.com.cn
- Recruiting
Henan Eye Institue, Henan, China
Zhengzhou, Henan, 450003
Liya wang, MD, 0086-13937169191, wangliya55@126.com
About this study
Official title: The Effect of Prednisone Versus Doxycycline in Active, Moderately Severe Graves' Orbitopathy: A Randomized, Multi-center, Double-blind, Parallel-controlled Trial
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).
Read the 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.
- Conditions
- Thyroid Associated Opthalmopathies
- Being tested
- Prednisone+placebo of Doxycycline, Doxycycline+placebo of Prednisone
- Medical subject headings
- Graves Ophthalmopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prednisone+placebo of DoxycyclineDrug
Also called deltacortisone
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+placebo of PrednisoneDrug
Also called Dolotard, Tibirox, Biomycin
Doxycycline: 50 mg PO per day for 12 weeks, and placebo for another 4 weeks; Placebo of prednisone: administered for 16 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Prednisone+placebo of Doxycycline | Active comparator | 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. Receives: Drug: Prednisone+placebo of Doxycycline |
| Doxycycline+placebo of Prednisone | Experimental | Doxycycline: 50 mg/d for 12 weeks, and placebo for another 4 weeks; Placebo of prednisone: administered for 16 weeks. Receives: Drug: Doxycycline+placebo of Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (4)
• Health related quality of life questionnaires (GO-QoL)
Measured: 24 weeks
• Safety and tolerability as assessed by adverse events, vital signs
Measured: 48 weeks
• Quantitative changes of rectus diameter measured by MRI scan
Measured: 24 weeks
Relapse
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2013 (estimated)
- Study startNov 2012
- Primary completionJan 2016 (estimated)
- Study completionJan 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thyroid Associated OpthalmopathiesStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 146 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dan Liang, Sun Yat-sen University
- Investigators
- Dan Liang, MD, Study chair, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaLiya Wang, MD, Principal investigator, Henan Eye Institue, Henan, ChinaLuosheng Tang, MD, Principal investigator, The second xiangya hospital of central south university, Hunan, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01809444
- Sponsor's protocol ID
- 5010-doxy
- Status last verified
- Dec 2013
- First submitted
- 2 Dec 2012
- Last updated
- 10 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Prednisone Versus Doxycycline in Active, Moderately Severe Graves' Orbitopathy: A Randomized, Multi-center, Double-blind, Parallel-controlled Trial
- ClinicalTrials.gov ID
- NCT01809444
- Acronym / sponsor ID
- 5010-doxy
- Conditions
- Thyroid Associated Opthalmopathies
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 146 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- Jan 2016 (estimated)
- Study completion
- Jan 2016 (estimated)
- First posted
- 12 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prednisone+placebo of Doxycycline | Active comparator | Drug: Prednisone+placebo of DoxycyclinePrednisone: 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+placebo of Prednisone | Experimental | Drug: Doxycycline+placebo of PrednisoneDoxycycline: 50 mg/d for 12 weeks, and placebo for another 4 weeks; Placebo of prednisone: administered for 16 weeks. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Confirmed diagnosis of Graves' Orbitopathy (as defined by Bartley and Gorman)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prednisone+placebo of DoxycyclineAlso: deltacortisonePrednisone: 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 |
| Doxycycline+placebo of PrednisoneAlso: Dolotard, Tibirox, BiomycinDoxycycline: 50 mg PO per day for 12 weeks, and placebo for another 4 weeks; Placebo of prednisone: administered for 16 weeks. | Drug | Doxycycline+placebo of Prednisone |
Primary outcome
Overall treatment response
Time frame: 24 weeks
Overall treatment response was graded as: improvement, deterioration, and no success. 1. 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. 2. 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. 3. No success was defined if there was no change or the changes did not reach the improvement criteria.
4 secondary outcomes
• 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2013.
- Genetics Home Reference related topics: Lenz microphthalmia syndrome oculofaciocLink provided by the sponsor.
- MedlinePlus related topics: Antibiotics Eye Diseases Thyroid DiseasesLink provided by the sponsor.
- U.S. FDA ResourcesLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dan Liang, MD study chair
Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
Liya Wang, MD principal investigator
Henan Eye Institue, Henan, China
Luosheng Tang, MD principal investigator
The second xiangya hospital of central south university, Hunan, China
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study of Thyroid Associated Opthalmopathies, run by Sun Yat-sen University at 6 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dan Liang, MD (0086-20-87331766, liangd2@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall treatment response (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2013.