search
Back to results

Doxycycline Treatment in Mild Thyroid-Associated Ophthalmopathy

Primary Purpose

Graves Ophthalmopathy, Graves Disease, Thyroid-associated Ophthalmopathy

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Doxycycline hyclate
Placebo
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graves Ophthalmopathy focused on measuring Graves' orbitopathy, Graves´ ophthalmopathy, Thyroid eye disease, Thyroid-associated ophthalmopathy, Doxycycline, EUGOGO, CAS

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Zhongshan Ophthalmic CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Doxycycline

Placebo

Arm Description

Tablets Doxycycline 50 mg PO per day for 12 weeks

Tablet placebo for 12 weeks

Outcomes

Primary Outcome Measures

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%.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
July 28, 2014
Last Updated
November 16, 2021
Sponsor
Sun Yat-sen University
search

1. Study Identification

Unique Protocol Identification Number
NCT02203682
Brief Title
Doxycycline Treatment in Mild Thyroid-Associated Ophthalmopathy
Official Title
The Effect of Subantimicrobial Dose Doxycycline in Mild Thyroid-Associated Ophthalmopathy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Unknown status
Study Start Date
July 2014 (undefined)
Primary Completion Date
July 2022 (Anticipated)
Study Completion Date
July 2022 (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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graves Ophthalmopathy, Graves Disease, Thyroid-associated Ophthalmopathy, Thyroid Diseases, Endocrine System Diseases, Eye Diseases, Hereditary, Hyperthyroidism, Autoimmune Diseases, Immune System Diseases
Keywords
Graves' orbitopathy, Graves´ ophthalmopathy, Thyroid eye disease, Thyroid-associated ophthalmopathy, Doxycycline, EUGOGO, CAS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Doxycycline
Arm Type
Experimental
Arm Description
Tablets Doxycycline 50 mg PO per day for 12 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Tablet placebo for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Doxycycline hyclate
Intervention Description
Tab. Doxycycline 50 mg PO per day for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablet placebo for 12 weeks
Primary Outcome Measure Information:
Title
the rate of improvement
Description
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%.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Clinical Activity Score (CAS)
Description
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.
Time Frame
4weeks and 12 weeks
Title
Proptosis measured by Hertel instrument
Description
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.
Time Frame
4weeks and 12 weeks
Title
Eyelid aperture
Description
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.
Time Frame
4weeks and 12 weeks
Title
Lid retraction
Description
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.
Time Frame
4weeks and 12 weeks
Title
Lid lag
Description
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.
Time Frame
4weeks and 12 weeks
Title
Eye motility
Description
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.
Time Frame
4weeks and 12 weeks
Title
Graves' Ophthalmopathy Quality of Life Scale
Description
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.
Time Frame
4weeks and 12 weeks
Title
C-OSDI
Description
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.
Time Frame
4weeks and 12 weeks
Title
the category of adverse events and the frequency of the occurrence of adverse events
Description
The category of adverse events and the frequency of the occurrence of adverse events are listed to describe the safety.
Time Frame
4weeks and 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dan Liang, MD
Phone
0086-20-87331766
Email
linml0754@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan Liang, MD
Organizational Affiliation
Zhongsh Ophthalmic Center
Official's Role
Principal Investigator
Facility Information:
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

12. IPD Sharing Statement

Citations:
PubMed Identifier
36173609
Citation
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.
Results Reference
derived

Learn more about this trial

Doxycycline Treatment in Mild Thyroid-Associated Ophthalmopathy

We'll reach out to this number within 24 hrs