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

NCT01727973 | Completed Phase 1 DMC

• 1 other identifier: GO-DOXY-1
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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).

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

Outcome Measures

Primary Outcomes (1)

• • 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

Secondary Outcomes (2)

• Safety and tolerability as assessed by adverse events, vital signs

  24 weeks

• Graves' orbitopathy-Specific Quality of Life (GO-QoL)

  24 weeks

Study Arms (1)

Doxycycline

EXPERIMENTAL

Tablets Doxycycline 50 mg PO per day for 12 weeks

Drug: Doxycycline

Interventions

Doxycycline DRUG

Tab. Doxycycline 50 mg PO per day for 12 weeks

Also known as: Dolotard, Tibirox, Biomycin

Doxycycline

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Must be able to swallow tablets
• Written informed consent is obtained

You may not qualify if:

• 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

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Zhongshan Ophthalmic Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (1)

• 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.

  PMID: 26221138 DERIVED

Related Links

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

MeSH Terms

Conditions

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

Interventions

Doxycycline; sulfadiazine, tetroxoprim drug combination; Chlortetracycline

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Dan Liang, MD

  Zhongsh Ophthalmic Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 12, 2012
• First Posted: November 16, 2012
• Study Start: October 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: December 10, 2013

Record last verified: 2013-12

Locations

CN (1)