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

Sponsor
Sun Yat-sen University (Other)
Overall Status
Completed
CT.gov ID
NCT01727973
Collaborator
(none)
14
1
1
13
1.1

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 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
14 participants
Allocation:
N/A
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 :
Oct 1, 2012
Actual Primary Completion Date :
Nov 1, 2013
Actual Study Completion Date :
Nov 1, 2013

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. • Treatment response [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 [24 weeks]

    2. Graves' orbitopathy-Specific Quality of Life (GO-QoL) [24 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Zhongshan Ophthalmic Center Guangzhou Guangdong China 510060

    Sponsors and Collaborators

    • Sun Yat-sen University

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Dan Liang, MD, Sun Yat-sen University
    ClinicalTrials.gov Identifier:
    NCT01727973
    Other Study ID Numbers:
    • GO-DOXY-1
    First Posted:
    Nov 16, 2012
    Last Update Posted:
    Dec 10, 2013
    Last Verified:
    Dec 1, 2013

    Study Results

    No Results Posted as of Dec 10, 2013