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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dan Liang, Sun Yat-sen University
ClinicalTrials.gov Identifier:
NCT01727973
First received: November 12, 2012
Last updated: December 7, 2013
Last verified: December 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Sun Yat-sen University:

Primary Outcome Measures:
  • • Treatment response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Graves' orbitopathy-Specific Quality of Life (GO-QoL) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: October 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01727973

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

Additional Information:
No publications provided

Responsible Party: Dan Liang, MD, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT01727973     History of Changes
Other Study ID Numbers: GO-DOXY-1
Study First Received: November 12, 2012
Last Updated: December 7, 2013
Health Authority: China: Ethics Committee

Keywords provided by Sun Yat-sen University:
Graves' orbitopathy
Graves´ ophthalmopathy
Thyroid eye disease
Thyroid-associated ophthalmopathy
Doxycycline
EUGOGO
CAS

Additional relevant MeSH terms:
Autoimmune Diseases
Endocrine System Diseases
Eye Diseases
Eye Diseases, Hereditary
Genetic Diseases, Inborn
Graves Disease
Graves Ophthalmopathy
Hyperthyroidism
Immune System Diseases
Thyroid Diseases
Exophthalmos
Goiter
Orbital Diseases
Doxycycline
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014