Graves OphthalmopathyPhase 1/2NCT01727973
Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy
A Phase 1/2 study testing Doxycycline 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 wk, for patients with 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
- Graves Ophthalmopathy, Graves Disease, Eye Diseases
- What is being tested?
- Doxycycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteChina
- Study dates
- Oct 2012to Nov 2013
- Phase
- Phase 1/2
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Clinical diagnosis of Graves' Orbitopathy
- Moderate-severe GO According to EUGOGO statements, patients with moderate-severe GO usually have any one or more of the following：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 month 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 gonadotropin (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 Transaminase (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 allergy or intolerance
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy: a Prospective, Uncontrolled Pilot Study
The aim of this study is to evaluate the effects of subantimicrobial dose doxycycline (50 mg/d), administered for 12 wk, for patients with active moderate-severe Graves' Orbitopathy (GO).
Read the detailed description
Graves'orbitopathy is an autoimmune disease characterised 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, but they often cause severe side-effects.
Subantimicrobial 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 subantimicrobial dose doxycycline for rosacea, periodontitis and multiple sclerosis.
We propose to test the effect of subantimicrobial dose doxycycline for non-sight threatening, moderate-severe, inflammatory GO.
- Conditions
- Graves Ophthalmopathy, Graves Disease, Eye Diseases, Thyroid Diseases, Endocrine System Diseases, Eye Diseases, Hereditary
- Being tested
- Doxycycline
- Keywords
- Graves' orbitopathy, Graves´ ophthalmopathy, Thyroid eye disease, Thyroid-associated ophthalmopathy, Doxycycline, EUGOGO, CAS
- Medical subject headings
- Graves Ophthalmopathy, Graves Disease, Eye Diseases, Thyroid Diseases, Endocrine System Diseases, Eye Diseases, Hereditary, Hyperthyroidism, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
Also called Dolotard, Tibirox, Biomycin
Tab. Doxycycline 50 mg PO per day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline | Experimental | Tablets Doxycycline 50 mg PO per day for 12 weeks Receives: Drug: Doxycycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
• Treatment response
As definition of treatment response, we used the major and minor criteria . 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. A successful response was defined as an improvement in one or more major criteria or in two minor criteria, in absence of deterioration of any criterion in that observed eye. Deterioration was 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 success criteria.
Measured: 24 weeks
Secondary outcomes (2)
Safety and tolerability as assessed by adverse events, vital signs
Measured: 24 weeks
Graves' orbitopathy-Specific Quality of Life (GO-QoL)
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2012 (estimated)
- Study startOct 2012
- Primary completionNov 2013
- Study completionNov 2013
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
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
- NCT01727973
- Sponsor's protocol ID
- GO-DOXY-1
- Status last verified
- Dec 2013
- First submitted
- 12 Nov 2012
- Last updated
- 10 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lin M, Mao Y, Ai S, Liu G, Zhang J, Yan J, Yang H, Li A, Zou Y, Liang D. Efficacy of Subantimicrobial Dose Doxycycline for Moderate-to-Severe and Active Graves' Orbitopathy. Int J Endocrinol. 2015;2015:285698. doi: 10.1155/2015/285698. Epub 2015 Jun 29.
PubMed 26221138
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
- Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy: a Prospective, Uncontrolled Pilot Study
- ClinicalTrials.gov ID
- NCT01727973
- Acronym / sponsor ID
- GO-DOXY-1
- Conditions
- Graves Ophthalmopathy, Graves Disease, Eye Diseases, Thyroid Diseases, Endocrine System Diseases, Eye Diseases, Hereditary
- Keywords
- Graves' orbitopathy, Graves´ ophthalmopathy, Thyroid eye disease, Thyroid-associated ophthalmopathy, Doxycycline, EUGOGO, CAS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 16 Nov 2012 (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 wk, for patients with active moderate-severe Graves' Orbitopathy (GO).
Detailed description
Graves'orbitopathy is an autoimmune disease characterised 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, but they often cause severe side-effects.
Subantimicrobial 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 subantimicrobial dose doxycycline for rosacea, periodontitis and multiple sclerosis.
We propose to test the effect of subantimicrobial dose doxycycline for non-sight threatening, moderate-severe, inflammatory GO.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Doxycycline | Experimental | Drug: DoxycyclineTablets Doxycycline 50 mg PO per day for 12 weeks |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Clinical diagnosis of Graves' Orbitopathy
- Moderate-severe GO According to EUGOGO statements, patients with moderate-severe GO usually have any one or more of the following：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 month 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 gonadotropin (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 |
|---|---|---|
| DoxycyclineAlso: Dolotard, Tibirox, BiomycinTab. Doxycycline 50 mg PO per day for 12 weeks | Drug | Doxycycline |
Primary outcome
• Treatment response
Time frame: 24 weeks
As definition of treatment response, we used the major and minor criteria . 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. A successful response was defined as an improvement in one or more major criteria or in two minor criteria, in absence of deterioration of any criterion in that observed eye. Deterioration was 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 success criteria.
2 secondary outcomes
Safety and tolerability as assessed by adverse events, vital signs
Time frame: 24 weeks
Graves' orbitopathy-Specific Quality of Life (GO-QoL)
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2013.
- Derived from this study: PubMed 26221138Lin M, Mao Y, Ai S, Liu G, Zhang J, Yan J, Yang H, Li A, Zou Y, Liang D. Efficacy of Subantimicrobial Dose Doxycycline for Moderate-to-Severe and Active Graves' Orbitopathy. Int J Endocrinol. 2015;2015:285698. doi: 10.1155/2015/285698. Epub 2015 Jun 29.
- Genetics Home Reference related topics: Lenz microphthalmia syndrome oculofaciocardiodental syndrome Peters plus syndromeLink provided by the sponsor.
- MedlinePlus related topics: Antibiotics Eye Diseases Thyroid DiseasesLink provided by the sponsor.
- Drug Information available for: Doxycycline Dolotard Tibirox BiomycinLink 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 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 1/2 study testing Doxycycline 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 6 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: finished, 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 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• 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?
On the ClinicalTrials.gov record for NCT01727973, 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 10 Dec 2013.