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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy: a Prospective, Uncontrolled Pilot Study

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 Summary:

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.


Sponsor: Sun Yat-sen University

Current Primary Outcome: • 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.


Original Primary Outcome: • European Group on Graves' Orbitopathy (EUGOGO) Clinical Activity Score [ Time Frame: Primary study measures - 6 months ]

Clinical Activity Score is a validated index of Graves' orbitopathy that assigns one point to the presence of: 1.spontaneous retrobulbar pain, 2. pain on up/downgaze, 3. redness of eyelids, 4. redness of conjunctiva, 5. swelling of eyelids, 6. inflammation of caruncle/plica, 7. chemosis. The maximal clinical activity score (CAS) is thus 7.


Current Secondary Outcome:

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


Original Secondary Outcome: • Health related quality of life questionnaires (GO-QoL) [ Time Frame: Primary study measures - 6 months ]

Information By: Sun Yat-sen University

Dates:
Date Received: November 12, 2012
Date Started: October 2012
Date Completion:
Last Updated: December 7, 2013
Last Verified: December 2013