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

Autoimmune Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01727973
• Other study ID #: GO-DOXY-1
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 12, 2012
• Last updated: December 7, 2013
• Start date: October 2012
• Est. completion date: November 2013

Study information

• Verified date: December 2013
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autoimmune Diseases
• Endocrine System Diseases
• Eye Diseases
• Eye Diseases, Hereditary
• Graves Disease
• Graves Ophthalmopathy
• Hyperthyroidism
• Immune System Diseases
• Thyroid Diseases

Intervention

Drug:
• Doxycycline
Tab. Doxycycline 50 mg PO per day for 12 weeks

Locations

Country	Name	City	State
China	Zhongshan Ophthalmic Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	• 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.	24 weeks	No
Secondary	Safety and tolerability as assessed by adverse events, vital signs		24 weeks	Yes
Secondary	Graves' orbitopathy-Specific Quality of Life (GO-QoL)		24 weeks	No

External Links

•   Drug Information available for: Doxycycline Dolotard Tibirox Biomycin
•   Genetics Home Reference related topics: Lenz microphthalmia syndrome oculofaciocardiodental syndrome Peters plus syndrome
•   MedlinePlus related topics: Antibiotics Eye Diseases Thyroid Diseases
•   U.S. FDA Resources