<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01727973</url>
  </required_header>
  <id_info>
    <org_study_id>GO-DOXY-1</org_study_id>
    <nct_id>NCT01727973</nct_id>
  </id_info>
  <brief_title>Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy</brief_title>
  <official_title>Efficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves' Orbitopathy: a Prospective, Uncontrolled Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to evaluate the effects of subantimicrobial dose doxycycline (50&#xD;
      mg/d), administered for 12 wk, for patients with active moderate-severe Graves' Orbitopathy&#xD;
      (GO).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Graves'orbitopathy is an autoimmune disease characterised by an inflammatory phase followed&#xD;
      by fibrosis. Surgery to correct eyelid swelling, proptosis, and diplopia is effective, but&#xD;
      can not be done until the inflammatory phase has passed. To arrest the inflammatory phase,&#xD;
      several types of immunosuppressive treatments have been investigated. Corticosteroids are the&#xD;
      first-choice immunosuppressive treatment, but they often cause severe side-effects.&#xD;
&#xD;
      Subantimicrobial dose doxycycline posses known anti-inflammatory effects that are separate&#xD;
      from their antibacterial mode of action. This mode of action has lead to the routine use of&#xD;
      subantimicrobial dose doxycycline for rosacea, periodontitis and multiple sclerosis.&#xD;
&#xD;
      We propose to test the effect of subantimicrobial dose doxycycline for non-sight threatening,&#xD;
      moderate-severe, inflammatory GO.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">November 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>• Treatment response</measure>
    <time_frame>24 weeks</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability as assessed by adverse events, vital signs</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graves' orbitopathy-Specific Quality of Life (GO-QoL)</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Graves Ophthalmopathy</condition>
  <condition>Graves Disease</condition>
  <condition>Eye Diseases</condition>
  <condition>Thyroid Diseases</condition>
  <condition>Endocrine System Diseases</condition>
  <condition>Eye Diseases, Hereditary</condition>
  <condition>Hyperthyroidism</condition>
  <condition>Autoimmune Diseases</condition>
  <condition>Immune System Diseases</condition>
  <arm_group>
    <arm_group_label>Doxycycline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablets Doxycycline 50 mg PO per day for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxycycline</intervention_name>
    <description>Tab. Doxycycline 50 mg PO per day for 12 weeks</description>
    <arm_group_label>Doxycycline</arm_group_label>
    <other_name>Dolotard</other_name>
    <other_name>Tibirox</other_name>
    <other_name>Biomycin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of Graves' Orbitopathy&#xD;
&#xD;
          -  Moderate-severe GO According to EUGOGO statements, patients with moderate-severe GO&#xD;
             usually have any one or more of the following：moderate or severe soft tissue&#xD;
             involvement, exophthalmos≥3mm above normal for race and gender, inconstant, or&#xD;
             constant diplopia.&#xD;
&#xD;
          -  Clinical activity score ≥ 3&#xD;
&#xD;
          -  Being euthyroid for at least 1 month before the date of inclusion&#xD;
&#xD;
          -  Must be able to swallow tablets&#xD;
&#xD;
          -  Written informed consent is obtained&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Mild Graves' Orbitopathy&#xD;
&#xD;
          -  Sight-threatening Graves' Orbitopathy&#xD;
&#xD;
          -  Clinical activity score &lt; 3&#xD;
&#xD;
          -  Previous treatment for GO Oral steroids, intravenous steroids, radiotherapy&#xD;
&#xD;
          -  Pregnant females as determined by positive (serum or urine) Human chorionic&#xD;
             gonadotropin (hCG) test at screening or prior to dosing, or lactating females&#xD;
&#xD;
          -  Uncontrolled diabetes or hypertension&#xD;
&#xD;
          -  History of mental / psychiatric disorder&#xD;
&#xD;
          -  Hepatic dysfunction (Albumin (Alb),Aspartate Transaminase (AST), Alanine&#xD;
             Aminotransferase (ALT) and Alkaline phosphates levels must be within normal range for&#xD;
             eligibility)&#xD;
&#xD;
          -  Renal impairment (Urea and Creatinine levels must be within normal range)&#xD;
&#xD;
          -  Doxycycline allergy or intolerance&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dan Liang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zhongsh Ophthalmic Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Zhongshan Ophthalmic Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://ghr.nlm.nih.gov/</url>
    <description>Genetics Home Reference related topics: Lenz microphthalmia syndrome oculofaciocardiodental syndrome Peters plus syndrome</description>
  </link>
  <link>
    <url>http://www.nlm.nih.gov/medlineplus</url>
    <description>MedlinePlus related topics: Antibiotics Eye Diseases Thyroid Diseases</description>
  </link>
  <link>
    <url>http://druginfo.nlm.nih.gov/drugportal/drugportal.jsp</url>
    <description>Drug Information available for: Doxycycline Dolotard Tibirox Biomycin</description>
  </link>
  <link>
    <url>http://www.clinicaltrials.gov/ct2/info/fdalinks</url>
    <description>U.S. FDA Resources</description>
  </link>
  <verification_date>December 2013</verification_date>
  <study_first_submitted>November 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 16, 2012</study_first_posted>
  <last_update_submitted>December 7, 2013</last_update_submitted>
  <last_update_submitted_qc>December 7, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 10, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Dan Liang</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Graves' orbitopathy</keyword>
  <keyword>Graves´ ophthalmopathy</keyword>
  <keyword>Thyroid eye disease</keyword>
  <keyword>Thyroid-associated ophthalmopathy</keyword>
  <keyword>Doxycycline</keyword>
  <keyword>EUGOGO</keyword>
  <keyword>CAS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Eye Diseases</mesh_term>
    <mesh_term>Graves Disease</mesh_term>
    <mesh_term>Graves Ophthalmopathy</mesh_term>
    <mesh_term>Eye Diseases, Hereditary</mesh_term>
    <mesh_term>Genetic Diseases, Inborn</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
    <mesh_term>Endocrine System Diseases</mesh_term>
    <mesh_term>Hyperthyroidism</mesh_term>
    <mesh_term>Autoimmune Diseases</mesh_term>
    <mesh_term>Immune System Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxycycline</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01727973
org study id: GO-DOXY-1
nct id: NCT01727973
lead sponsor: 
has dmc: Yes
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).
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: • Treatment response
time frame: 24 weeks
description: 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.
measure: Safety and tolerability as assessed by adverse events, vital signs
time frame: 24 weeks
measure: Graves' orbitopathy-Specific Quality of Life (GO-QoL)
time frame: 24 weeks
arm group label: Doxycycline
arm group type: Experimental
description: Tablets Doxycycline 50 mg PO per day for 12 weeks
intervention type: Drug
intervention name: Doxycycline
description: Tab. Doxycycline 50 mg PO per day for 12 weeks
arm group label: Doxycycline
other name: Dolotard
other name: Tibirox
other name: Biomycin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Dan Liang, MD
role: Principal Investigator
affiliation: Zhongsh Ophthalmic Center
facility: 
country: China
url: http://ghr.nlm.nih.gov/
description: Genetics Home Reference related topics: Lenz microphthalmia syndrome oculofaciocardiodental syndrome Peters plus syndrome
url: http://www.nlm.nih.gov/medlineplus
description: MedlinePlus related topics: Antibiotics Eye Diseases Thyroid Diseases
url: http://druginfo.nlm.nih.gov/drugportal/drugportal.jsp
description: Drug Information available for: Doxycycline Dolotard Tibirox Biomycin
url: http://www.clinicaltrials.gov/ct2/info/fdalinks
description: U.S. FDA Resources
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Dan Liang
investigator title: MD
mesh term: Eye Diseases
mesh term: Graves Disease
mesh term: Graves Ophthalmopathy
mesh term: Eye Diseases, Hereditary
mesh term: Genetic Diseases, Inborn
mesh term: Thyroid Diseases
mesh term: Endocrine System Diseases
mesh term: Hyperthyroidism
mesh term: Autoimmune Diseases
mesh term: Immune System Diseases
mesh term: Doxycycline