Graves OphthalmopathyPhase 2NCT02203682
Doxycycline Treatment in Mild Thyroid-Associated Ophthalmopathy
A Phase 2 study testing Doxycycline hyclate in people with Graves Ophthalmopathy and Graves Disease, run by Sun Yat-sen University at 1 site in China.
Trial summary
The aim of this study is to evaluate the effects of subantimicrobial dose doxycycline (50 mg/d), administered for 12 weeks, on patients with mild Thyroid-Associated Ophthalmopathy (TAO). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Graves Ophthalmopathy, Graves Disease, Thyroid-associated Ophthalmopathy
- What is being tested?
- Doxycycline hyclate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- Jul 2014to Jul 2022
- Phase
- Phase 2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of Thyroid-associated ophthalmopathy
- Mild TAO
- Normal serum free thyroxine and free triiodothyronine concentrations
- No previous specific therapy for TAO, except for local measures
- Written informed consent is obtained
Who cannot join
- Pregnant females as determined by positive (serum or urine) hCG test at screening or prior to dosing, or lactating females
- Uncontrolled diabetes or hypertension
- History of mental / psychiatric disorder
- Hepatic dysfunction (Alb, AST, ALT and Alkaline phosphates levels must be within normal range for eligibility)
- Renal impairment (Urea and Creatinine levels must be within normal range)
- Tetracycline allergy or intolerance
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhongshan Ophthalmic Center
Guangzhou, Guangdong, 510060
Dan Liang, MD, 0086-20-87331766, liangd2@mail.sysu.edu.cn
About this study
Official title: The Effect of Subantimicrobial Dose Doxycycline in Mild Thyroid-Associated Ophthalmopathy
The aim of this study is to evaluate the effects of subantimicrobial dose doxycycline (50 mg/d), administered for 12 weeks, on patients with mild Thyroid-Associated Ophthalmopathy (TAO).
Read the detailed description
Thyroid-Associated Ophthalmopathy is an autoimmune disease that can be treated by corticosteroids and surgery. But they often cause severe side-effects and are usually used for treating moderate-sever and sight-threatening TAO. Wait and see will be the first choice for the patient with mild TAO.
Subantimicrobial dose (SD) doxycycline displays a strong anti-inflammatory and immunomodulatory function, which is independent of its antibiotic properties. Data from clinical trials demonstrated that SD doxycycline was effective in moderating inflammation in a variety of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, rosacea and periodontitis.
We propose to test the effect of subantimicrobial dose doxycycline for mild TAO.
- Conditions
- Graves Ophthalmopathy, Graves Disease, Thyroid-associated Ophthalmopathy, Thyroid Diseases, Endocrine System Diseases, Eye Diseases, Hereditary
- Being tested
- Doxycycline hyclate, Placebo
- Keywords
- Graves' orbitopathy, Graves´ ophthalmopathy, Thyroid eye disease, Thyroid-associated ophthalmopathy, Doxycycline, EUGOGO, CAS
- Medical subject headings
- Graves Ophthalmopathy, Graves Disease, Thyroid Diseases, Endocrine System Diseases, Eye Diseases, Hereditary, Hyperthyroidism, Autoimmune Diseases, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Doxycycline hyclateDrug
Tab. Doxycycline 50 mg PO per day for 12 weeks
PlaceboDrug
Tablet placebo for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline | Experimental | Tablets Doxycycline 50 mg PO per day for 12 weeks Receives: Drug: Doxycycline hyclate |
| Placebo | Placebo comparator | Tablet placebo for 12 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
the rate of improvement
Improvement was defined that at least one item was met in the study eye without deterioration in any item of both eyes:
- reduction of eyelid aperture by at least 2mm;
- reduction in exophthalmos by at least 2mm;
- increase in ocular motility by at least 8 degrees in any duction;
- increase on either GO-QOL scales by at least 6 points. The higher of the rate of improvement gets, the better the outcome is. The primary outcome ranges from -100% to 100%.
Measured: 12 weeks
Secondary outcomes (9)
Clinical Activity Score (CAS)
Patients will be assessed according to the 7 item European Group on Graves' Ophthalmopathy (EUGOGO) amended Clinical Activity Score (CAS) For each item present, one point is given. The sum of the points is the total score ranges from 0 to 7.
- Spontaneous orbital pain.
- Gaze evoked orbital pain.
- Eyelid swelling that is considered to be due to active (inflammatory phase) GO.
- Eyelid erythema.
- Conjunctival redness that is considered to be due to active (inflammatory phase) GO (ignore "equivocal" redness).
- Chemosis.
- Inflammation of caruncle or plica.
Measured: 4weeks and 12 weeks
Proptosis measured by Hertel instrument
For the assessment of proptosis, the same Hertel instrument and ideally the same observer should be used on each occasion. Additionally the same intercanthal distance (ICD) should be used on each occasion. The Hertel values will be measured for each eye at each visit and repeated three times. The mean value is recorded. Proptosis ranges from 10mm to 30mm.
Measured: 4weeks and 12 weeks
Eyelid aperture
For the assessment of eyelid aperture, the same millimeter ruler should be used by the same observer. These measurements are repeated three times, and the mean value is recorded. When performed this assessment, participants should relax their eyes and keep looking ahead and the observers should keep the ruler perpendicular to their eyelid.
Measured: 4weeks and 12 weeks
Lid retraction
For the assessment of eyelid aperture, the same millimeter ruler should be used by the same observer. The upper eyelid positions above (positive value) and below (negative value) the superior limbus and The lower eyelid positions above (positive value) and below (negative value) the posterior limbus were measured in millimeters in primary position. These measurements are repeated three times, and the mean value is recorded.
Measured: 4weeks and 12 weeks
Lid lag
For the assessment of eyelid aperture, the same millimeter ruler should be used by the same observer. Lid lag is defined that the lid margin distance in downgaze. The upper eyelid positions above (positive value) and below (negative value) the superior limbus were measured in millimeters.
Measured: 4weeks and 12 weeks
Eye motility
The head of each participant is adjusted to fix on the modified perimeter to set the visual axis of the examined eye on the center of the optimal visual target in visual chart. The other eye should be covered. The examined eye should follow the movement of the visual target until the participant cannot identify the exact visual target in vertical and horizontal directions. And the extreme scales of these four directions are obtained. These measurements are repeated three times, and the mean value is recorded.
Measured: 4weeks and 12 weeks
Graves' Ophthalmopathy Quality of Life Scale
The Graves' Ophthalmopathy Quality of Life (GO-QOL) questionnaire (Terwee \& al, 1998) includes visual functioning and psychosocial functioning. A raw score of each part is calculated by adding each score of 8 question, namely 1, 2, or 3 for each question which means marked, mild, or absent limitation, the final score ranging from 0 (full limitation) to 100 (no limitation) is calculated as the following rule: (raw score - 8) ÷ 16 × 100]. GO-QOL will be completed at screening, weeks 0, 4, 12. were also recorded to assess activity of TAO and impact on quality of life respectively.
The GO-QOL is a 16 item self-administered questionnaire used to assess the perceived effects of TAO by the patients on their daily physical and psychosocial functioning.
Measured: 4weeks and 12 weeks
C-OSDI
The Ocular Surface Disease Index (OSDI), developed by the Outcomes Research Group at Allergan Inc (Irvine, Calif), is a 12-item questionnaire designed to provide a rapid assessment of the symptoms of ocular irritation and vision-related functioning.
Measured: 4weeks and 12 weeks
the category of adverse events and the frequency of the occurrence of adverse events
The category of adverse events and the frequency of the occurrence of adverse events are listed to describe the safety.
Measured: 4weeks and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionJul 2022 (estimated)
- Study completionJul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graves OphthalmopathyStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 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, Principal investigator, Zhongsh Ophthalmic Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02203682
- Sponsor's protocol ID
- 2013MEKY033
- Status last verified
- Oct 2021
- First submitted
- 28 Jul 2014
- Last updated
- 17 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pan Y, Chen YX, Zhang J, Lin ML, Liu GM, Xu XL, Fan XQ, Zhong Y, Li Q, Ai SM, Xu W, Tan J, Zhou HF, Xu DD, Zhang HY, Xu B, Wang S, Ma JJ, Zhang S, Gan LY, Cui JT, Li L, Xie YY, Guo X, Pan-Doh N, Zhu ZT, Lu Y, Shi YX, Xia YW, Li ZY, Liang D. Doxycycline vs Placebo at 12 Weeks in Patients With Mild Thyroid-Associated Ophthalmopathy: A Randomized Clinical Trial. JAMA Ophthalmol. 2022 Nov 1;140(11):1076-1083. doi: 10.1001/jamaophthalmol.2022.3779.
PubMed 36173609
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Subantimicrobial Dose Doxycycline in Mild Thyroid-Associated Ophthalmopathy
- ClinicalTrials.gov ID
- NCT02203682
- Acronym / sponsor ID
- 2013MEKY033
- Conditions
- Graves Ophthalmopathy, Graves Disease, Thyroid-associated Ophthalmopathy, Thyroid Diseases, Endocrine System Diseases, Eye Diseases, Hereditary
- Keywords
- Graves' orbitopathy, Graves´ ophthalmopathy, Thyroid eye disease, Thyroid-associated ophthalmopathy, Doxycycline, EUGOGO, CAS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 30 Jul 2014 (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 evaluate the effects of subantimicrobial dose doxycycline (50 mg/d), administered for 12 weeks, on patients with mild Thyroid-Associated Ophthalmopathy (TAO).
Detailed description
Thyroid-Associated Ophthalmopathy is an autoimmune disease that can be treated by corticosteroids and surgery. But they often cause severe side-effects and are usually used for treating moderate-sever and sight-threatening TAO. Wait and see will be the first choice for the patient with mild TAO.
Subantimicrobial dose (SD) doxycycline displays a strong anti-inflammatory and immunomodulatory function, which is independent of its antibiotic properties. Data from clinical trials demonstrated that SD doxycycline was effective in moderating inflammation in a variety of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, rosacea and periodontitis.
We propose to test the effect of subantimicrobial dose doxycycline for mild TAO.
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 |
|---|---|---|
| Doxycycline | Experimental | Drug: Doxycycline hyclateTablets Doxycycline 50 mg PO per day for 12 weeks |
| Placebo | Placebo comparator | Drug: PlaceboTablet placebo for 12 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Clinical diagnosis of Thyroid-associated ophthalmopathy
- Mild TAO
- Normal serum free thyroxine and free triiodothyronine concentrations
- No previous specific therapy for TAO, except for local measures
- Written informed consent is obtained
Key exclusion criteria (6 listed)
- Pregnant females as determined by positive (serum or urine) hCG test at screening or prior to dosing, or lactating females
- Uncontrolled diabetes or hypertension
- History of mental / psychiatric disorder
- Hepatic dysfunction (Alb, AST, ALT and Alkaline phosphates levels must be within normal range for eligibility)
- Renal impairment (Urea and Creatinine levels must be within normal range)
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 |
|---|---|---|
| Doxycycline hyclateTab. Doxycycline 50 mg PO per day for 12 weeks | Drug | Doxycycline |
| PlaceboTablet placebo for 12 weeks | Drug | Placebo |
Primary outcome
the rate of improvement
Time frame: 12 weeks
Improvement was defined that at least one item was met in the study eye without deterioration in any item of both eyes: 1. reduction of eyelid aperture by at least 2mm; 2. reduction in exophthalmos by at least 2mm; 3. increase in ocular motility by at least 8 degrees in any duction; 4. increase on either GO-QOL scales by at least 6 points. The higher of the rate of improvement gets, the better the outcome is. The primary outcome ranges from -100% to 100%.
9 secondary outcomes
Clinical Activity Score (CAS)
Time frame: 4weeks and 12 weeks
Proptosis measured by Hertel instrument
Time frame: 4weeks and 12 weeks
Eyelid aperture
Time frame: 4weeks and 12 weeks
Lid retraction
Time frame: 4weeks and 12 weeks
Lid lag
Time frame: 4weeks and 12 weeks
Eye motility
Time frame: 4weeks and 12 weeks
Graves' Ophthalmopathy Quality of Life Scale
Time frame: 4weeks and 12 weeks
C-OSDI
Time frame: 4weeks and 12 weeks
the category of adverse events and the frequency of the occurrence of adverse events
Time frame: 4weeks and 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2021.
- Derived from this study: PubMed 36173609Pan Y, Chen YX, Zhang J, Lin ML, Liu GM, Xu XL, Fan XQ, Zhong Y, Li Q, Ai SM, Xu W, Tan J, Zhou HF, Xu DD, Zhang HY, Xu B, Wang S, Ma JJ, Zhang S, Gan LY, Cui JT, Li L, Xie YY, Guo X, Pan-Doh N, Zhu ZT, Lu Y, Shi YX, Xia YW, Li ZY, Liang D. Doxycycline vs Placebo at 12 Weeks in Patients With Mild Thyroid-Associated Ophthalmopathy: A Randomized Clinical Trial. JAMA Ophthalmol. 2022 Nov 1;140(11):1076-1083. doi: 10.1001/jamaophthalmol.2022.3779.
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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 principal investigator
Zhongsh Ophthalmic Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Doxycycline hyclate in people with Graves Ophthalmopathy and Graves Disease, run by Sun Yat-sen University at 1 site 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 5 inclusion and 6 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 17 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
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, linml0754@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the rate of improvement (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02203682, which also lists 1 linked publication.
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 17 Nov 2021; AzTrials last refreshed its copy on 6 Nov 2026.