Doxycycline Treatment in Mild Thyroid-Associated Ophthalmopathy

Sponsor
Sun Yat-sen University (Other)
Overall Status
Recruiting
CT.gov ID
NCT02203682
Collaborator
(none)
100
Enrollment
1
Location
2
Arms
96
Duration (Months)
1
Patients Per Site Per Month

Study Details

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
The Effect of Subantimicrobial Dose Doxycycline in Mild Thyroid-Associated Ophthalmopathy
Study Start Date :
Jul 1, 2014
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Jul 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Doxycycline

Tablets Doxycycline 50 mg PO per day for 12 weeks

Drug: Doxycycline hyclate
Tab. Doxycycline 50 mg PO per day for 12 weeks

Placebo Comparator: Placebo

Tablet placebo for 12 weeks

Drug: Placebo
Tablet placebo for 12 weeks

Outcome Measures

Primary Outcome Measures

  1. the rate of improvement [12 weeks]

    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

  1. Clinical Activity Score (CAS) [4weeks and 12 weeks]

    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.

  2. Proptosis measured by Hertel instrument [4weeks and 12 weeks]

    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.

  3. Eyelid aperture [4weeks and 12 weeks]

    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.

  4. Lid retraction [4weeks and 12 weeks]

    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.

  5. Lid lag [4weeks and 12 weeks]

    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.

  6. Eye motility [4weeks and 12 weeks]

    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.

  7. Graves' Ophthalmopathy Quality of Life Scale [4weeks and 12 weeks]

    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.

  8. C-OSDI [4weeks and 12 weeks]

    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.

  9. the category of adverse events and the frequency of the occurrence of adverse events [4weeks and 12 weeks]

    The category of adverse events and the frequency of the occurrence of adverse events are listed to describe the safety.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Zhongshan Ophthalmic CenterGuangzhouGuangdongChina510060

Sponsors and Collaborators

  • Sun Yat-sen University

Investigators

  • Principal Investigator: Dan Liang, MD, Zhongsh Ophthalmic Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Dan Liang, MD, Sun Yat-sen University
ClinicalTrials.gov Identifier:
NCT02203682
Other Study ID Numbers:
  • 2013MEKY033
First Posted:
Jul 30, 2014
Last Update Posted:
Nov 17, 2021
Last Verified:
Oct 1, 2021

Study Results

No Results Posted as of Nov 17, 2021