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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01727973
Recruitment Status : Completed
First Posted : November 16, 2012
Last Update Posted : December 10, 2013
Information provided by (Responsible Party):
Dan Liang, Sun Yat-sen University

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).

Condition or disease Intervention/treatment Phase
Graves Ophthalmopathy Graves Disease Eye Diseases Thyroid Diseases Endocrine System Diseases Eye Diseases, Hereditary Hyperthyroidism Autoimmune Diseases Immune System Diseases Drug: Doxycycline Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy: a Prospective, Uncontrolled Pilot Study
Study Start Date : October 2012
Actual Primary Completion Date : November 2013
Actual Study Completion Date : November 2013

Arm Intervention/treatment
Experimental: Doxycycline
Tablets Doxycycline 50 mg PO per day for 12 weeks
Drug: Doxycycline
Tab. Doxycycline 50 mg PO per day for 12 weeks
Other Names:
  • Dolotard
  • Tibirox
  • Biomycin

Primary Outcome Measures :
  1. • 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.

Secondary Outcome Measures :
  1. Safety and tolerability as assessed by adverse events, vital signs [ Time Frame: 24 weeks ]
  2. Graves' orbitopathy-Specific Quality of Life (GO-QoL) [ Time Frame: 24 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01727973

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China, Guangdong
Zhongshan Ophthalmic Center
Guangzhou, Guangdong, China, 510060
Sponsors and Collaborators
Sun Yat-sen University
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Principal Investigator: Dan Liang, MD Zhongsh Ophthalmic Center

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Dan Liang, MD, Sun Yat-sen University Identifier: NCT01727973     History of Changes
Other Study ID Numbers: GO-DOXY-1
First Posted: November 16, 2012    Key Record Dates
Last Update Posted: December 10, 2013
Last Verified: December 2013

Keywords provided by Dan Liang, Sun Yat-sen University:
Graves' orbitopathy
Graves´ ophthalmopathy
Thyroid eye disease
Thyroid-associated ophthalmopathy

Additional relevant MeSH terms:
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Eye Diseases
Autoimmune Diseases
Graves Disease
Immune System Diseases
Thyroid Diseases
Endocrine System Diseases
Genetic Diseases, Inborn
Eye Diseases, Hereditary
Orbital Diseases
Graves Ophthalmopathy
Anti-Bacterial Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents