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Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy

Primary Purpose

Graves Ophthalmopathy, Graves Disease, Eye Diseases

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Doxycycline
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 - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Sites / Locations

  • Zhongshan Ophthalmic Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Doxycycline

Arm Description

Tablets Doxycycline 50 mg PO per day for 12 weeks

Outcomes

Primary Outcome Measures

• 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.

Secondary Outcome Measures

Safety and tolerability as assessed by adverse events, vital signs
Graves' orbitopathy-Specific Quality of Life (GO-QoL)

Full Information

First Posted
November 12, 2012
Last Updated
December 7, 2013
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT01727973
Brief Title
Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy
Official Title
Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy: a Prospective, Uncontrolled Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graves Ophthalmopathy, Graves Disease, Eye Diseases, 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 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Doxycycline
Arm Type
Experimental
Arm Description
Tablets Doxycycline 50 mg PO per day for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Doxycycline
Other Intervention Name(s)
Dolotard, Tibirox, Biomycin
Intervention Description
Tab. Doxycycline 50 mg PO per day for 12 weeks
Primary Outcome Measure Information:
Title
• Treatment response
Description
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.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Safety and tolerability as assessed by adverse events, vital signs
Time Frame
24 weeks
Title
Graves' orbitopathy-Specific Quality of Life (GO-QoL)
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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
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

12. IPD Sharing Statement

Citations:
PubMed Identifier
26221138
Citation
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.
Results Reference
derived
Links:
URL
http://ghr.nlm.nih.gov/
Description
Genetics Home Reference related topics: Lenz microphthalmia syndrome oculofaciocardiodental syndrome Peters plus syndrome
URL
http://www.nlm.nih.gov/medlineplus
Description
MedlinePlus related topics: Antibiotics Eye Diseases Thyroid Diseases
URL
http://druginfo.nlm.nih.gov/drugportal/drugportal.jsp
Description
Drug Information available for: Doxycycline Dolotard Tibirox Biomycin
URL
http://www.clinicaltrials.gov/ct2/info/fdalinks
Description
U.S. FDA Resources

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Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy

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