Clinical trial NCT01727973: Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy
Official title: Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy: a Prospective, Uncontrolled Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Graves Ophthalmopathy
Graves Disease
Eye Diseases
Thyroid Diseases
Endocrine System Diseases
Eye Diseases, Hereditary
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases
Keywords: Graves' orbitopathy
Graves´ ophthalmopathy
Thyroid eye disease
Thyroid-associated ophthalmopathy
Doxycycline
EUGOGO
CAS
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2012-11-16
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: • Treatment response
timeFrame: 24 weeks
Secondary outcomes:
measure: Safety and tolerability as assessed by adverse events, vital signs
timeFrame: 24 weeks
measure: Graves' orbitopathy-Specific Quality of Life (GO-QoL)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhongshan Ophthalmic Center
state: Guangdong
Study officials:
affiliation: Zhongsh Ophthalmic Center
name: Dan Liang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lin M, Mao Y, Ai S, Liu G, Zhang J, Yan J, Yang H, Li A, Zou Y, Liang D. Efficacy of Subantimicrobial Dose Doxycycline for Moderate-to-Severe and Active Graves' Orbitopathy. Int J Endocrinol. 2015;2015:285698. doi: 10.1155/2015/285698. Epub 2015 Jun 29.