<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/NCT03011008</url>
  </required_header>
  <id_info>
    <org_study_id>0002</org_study_id>
    <nct_id>NCT03011008</nct_id>
  </id_info>
  <brief_title>Liraglutide as Additional Treatment to Insulin in Patients With Autoimmune Diabetes Mellitus</brief_title>
  <official_title>Effect of Liraglutide as Additional Treatment to Insulin in Patients With Autoimmune Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Second Xiangya Hospital of Central South University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Second Xiangya Hospital of Central South University</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the therapeutic effect of Liraglutide on&#xD;
      autoimmune diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Autoimmune Diabetes Mellitus (AIDM) is a subtype of diabetes mellitus caused by autoimmune&#xD;
      destruction of beta cells in the islet, including Type 1 diabetes and Latent Autoimmune&#xD;
      Diabetes in Adults (LADA). Insulin has been used as a routine therapy for AIDM to alleviate&#xD;
      the hyperglycemic status, yet cannot effectively prevent the progressing destruction of beta&#xD;
      cells or preserve its function. Glucagon-like peptide (GLP-1) analog Liraglutide has been&#xD;
      tested in large-scale clinical trial to prove its various benefits for beta cells and&#xD;
      glucolipid metabolism in Type 2 diabetes and obesity patients. However, its clinical&#xD;
      application in AIDM is not well-defined so far. The aim of this study is to investigate the&#xD;
      potential use of Liraglutide on glycemic control in AIDM.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">June 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean amplitude of glycemic excursions (MAGE)</measure>
    <time_frame>1 year</time_frame>
    <description>MAGE is measured by applying continuous glucose monitoring system (CGMS) on subjects in each follow-up of this one-year study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in HbA1C</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in C-peptide</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in insulin dose</measure>
    <time_frame>1 year</time_frame>
    <description>hyperglycemic and hypoglycemic events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hyperglycemic and hypoglycemic events</measure>
    <time_frame>1 year</time_frame>
    <description>Blood sugar level higher than 11.1 mmol/l or lower than 3.9 mmol/l.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Life quality evaluation</measure>
    <time_frame>1 year</time_frame>
    <description>Number of subjects with disturbance of emotion, sleep, resting or energy.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <condition>Autoimmune Diabetes</condition>
  <arm_group>
    <arm_group_label>Liraglutide + insulin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be subjected to a dose escalation of liraglutide up to 1.2 mg, then continue to receive the reached liraglutide dose once daily for 6 months thereafter. Insulin will be continued as routine therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Insulin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive insulin injection as a routine therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liraglutide</intervention_name>
    <description>Dose escalation of liraglutide starts from 0.6 mg up to 1.2 mg per day.</description>
    <arm_group_label>Liraglutide + insulin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin</intervention_name>
    <description>Receive insulin following clinician's instruction.</description>
    <arm_group_label>Insulin</arm_group_label>
    <arm_group_label>Liraglutide + insulin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes according to ADA criteria &lt;3 years.&#xD;
&#xD;
          -  Age≥ 18 years.&#xD;
&#xD;
          -  Positive for at least one of the anti-islet autoantibodies: GADA, IA2A, ZnT8A&#xD;
&#xD;
          -  Fasting or postprandial plasma C-peptide more than 100 pmol/L&#xD;
&#xD;
          -  Written informed consent from the patient or family representative&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or family history of medullary thyroid carcinoma or MEN 2 syndrome;&#xD;
&#xD;
          -  History of chronic or acute pancreatitis;&#xD;
&#xD;
          -  Allergic to liraglutide or any components in Victoza®;&#xD;
&#xD;
          -  Hepatic abnormalities (transaminase &gt; 2 times normal);&#xD;
&#xD;
          -  Renal impairments (serum creatinine &gt;133 umol/L);&#xD;
&#xD;
          -  Cardiovascular diseases (hypertension, coronary heart disease, etc.);&#xD;
&#xD;
          -  Presence of acute metabolic disorders; In the case of acute ketone acidosis, with&#xD;
             blood ketone over 0.3mmol/L and pH lower than 7.30;&#xD;
&#xD;
          -  Any history of malignancy;&#xD;
&#xD;
          -  Female patients who are pregnant or breastfeeding; any female who is unwilling to use&#xD;
             a reliable and effective form of contraception for 2 years after recruitment;&#xD;
&#xD;
          -  Presence of any infectious diseases, including active skin infections, flu, fever,&#xD;
             upper or lower respiratory tract infections; those who wish to participate in the&#xD;
             study should keep the infection under control for at least 1 week before receiving&#xD;
             Treg product infusion;&#xD;
&#xD;
          -  Any medical condition that, in the opinion of the investigator, will interfere with&#xD;
             safe participation in the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Zhiguang Zhou, MD/PhD</last_name>
    <phone>86-731-85292154</phone>
    <email>zhouzg@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410011</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhiguang Zhou, MD/PhD</last_name>
      <phone>86-731-85292154</phone>
      <email>zhouzg@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Rondas D, D'Hertog W, Overbergh L, Mathieu C. Glucagon-like peptide-1: modulator of beta-cell dysfunction and death. Diabetes Obes Metab. 2013 Sep;15 Suppl 3:185-92. doi: 10.1111/dom.12165.</citation>
    <PMID>24003936</PMID>
  </reference>
  <reference>
    <citation>Chang TJ, Tseng HC, Liu MW, Chang YC, Hsieh ML, Chuang LM. Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation. Sci Rep. 2016 Mar 21;6:23403. doi: 10.1038/srep23403. Erratum In: Sci Rep. 2016 May 31;6:26917.</citation>
    <PMID>26997114</PMID>
  </reference>
  <reference>
    <citation>Mathieu C, Gillard P. Arresting type 1 diabetes after diagnosis: GAD is not enough. Lancet. 2011 Jul 23;378(9788):291-2. doi: 10.1016/S0140-6736(11)60978-1. Epub 2011 Jun 27. No abstract available.</citation>
    <PMID>21715000</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>January 2, 2017</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>March 17, 2020</last_update_submitted>
  <last_update_submitted_qc>March 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Second Xiangya Hospital of Central South University</investigator_affiliation>
    <investigator_full_name>Zhiguang Zhou</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liraglutide</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/NCT03011008
org study id: 0002
nct id: NCT03011008
lead sponsor: 
The purpose of this study is to investigate the therapeutic effect of Liraglutide on
      autoimmune diabetes.
Autoimmune Diabetes Mellitus (AIDM) is a subtype of diabetes mellitus caused by autoimmune
      destruction of beta cells in the islet, including Type 1 diabetes and Latent Autoimmune
      Diabetes in Adults (LADA). Insulin has been used as a routine therapy for AIDM to alleviate
      the hyperglycemic status, yet cannot effectively prevent the progressing destruction of beta
      cells or preserve its function. Glucagon-like peptide (GLP-1) analog Liraglutide has been
      tested in large-scale clinical trial to prove its various benefits for beta cells and
      glucolipid metabolism in Type 2 diabetes and obesity patients. However, its clinical
      application in AIDM is not well-defined so far. The aim of this study is to investigate the
      potential use of Liraglutide on glycemic control in AIDM.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean amplitude of glycemic excursions (MAGE)
time frame: 1 year
description: MAGE is measured by applying continuous glucose monitoring system (CGMS) on subjects in each follow-up of this one-year study.
measure: Change in HbA1C
time frame: 1 year
measure: Change in C-peptide
time frame: 1 year
measure: Change in insulin dose
time frame: 1 year
description: hyperglycemic and hypoglycemic events.
measure: Hyperglycemic and hypoglycemic events
time frame: 1 year
description: Blood sugar level higher than 11.1 mmol/l or lower than 3.9 mmol/l.
measure: Life quality evaluation
time frame: 1 year
description: Number of subjects with disturbance of emotion, sleep, resting or energy.
arm group label: Liraglutide + insulin
arm group type: Experimental
description: Patients will be subjected to a dose escalation of liraglutide up to 1.2 mg, then continue to receive the reached liraglutide dose once daily for 6 months thereafter. Insulin will be continued as routine therapy.
arm group label: Insulin
arm group type: Active Comparator
description: Patients will receive insulin injection as a routine therapy.
intervention type: Drug
intervention name: Liraglutide
description: Dose escalation of liraglutide starts from 0.6 mg up to 1.2 mg per day.
arm group label: Liraglutide + insulin
intervention type: Drug
intervention name: Insulin
description: Receive insulin following clinician's instruction.
arm group label: Insulin
arm group label: Liraglutide + insulin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Zhiguang Zhou, MD/PhD
phone: 86-731-85292154
email: zhouzg@hotmail.com
facility: 
status: Recruiting
contact: 
country: China
citation: Rondas D, D'Hertog W, Overbergh L, Mathieu C. Glucagon-like peptide-1: modulator of beta-cell dysfunction and death. Diabetes Obes Metab. 2013 Sep;15 Suppl 3:185-92. doi: 10.1111/dom.12165.
PMID: 24003936
citation: Chang TJ, Tseng HC, Liu MW, Chang YC, Hsieh ML, Chuang LM. Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation. Sci Rep. 2016 Mar 21;6:23403. doi: 10.1038/srep23403. Erratum In: Sci Rep. 2016 May 31;6:26917.
PMID: 26997114
citation: Mathieu C, Gillard P. Arresting type 1 diabetes after diagnosis: GAD is not enough. Lancet. 2011 Jul 23;378(9788):291-2. doi: 10.1016/S0140-6736(11)60978-1. Epub 2011 Jun 27. No abstract available.
PMID: 21715000
responsible party type: Principal Investigator
investigator affiliation: Second Xiangya Hospital of Central South University
investigator full name: Zhiguang Zhou
investigator title: Principal Investigator
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Liraglutide