<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/NCT02226640</url>
  </required_header>
  <id_info>
    <org_study_id>TRIMDFH 238153</org_study_id>
    <nct_id>NCT02226640</nct_id>
  </id_info>
  <brief_title>Uncovering the 'ORIGINS' of Diabetes</brief_title>
  <acronym>ORIGINS</acronym>
  <official_title>Uncovering the 'ORIGINS' of Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AdventHealth Translational Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AdventHealth</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sanford-Burnham Medical Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>UCSF Benioff Children's Hospital Oakland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Duke Univeristy Sarah W. Stedman Nutrition &amp; Metabolism Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>AdventHealth Translational Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study to identify different subtypes of type 2 diabetes. The investigators will&#xD;
      look for information at the molecular level, which may lead to personalized diagnosis and&#xD;
      therapies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Type 2 diabetes mellitus (T2DM) is approaching epidemic prevalence in the US adult population&#xD;
      (over 1 in 10 of all US adults over 20). Diabetes is diagnosed based on fasting&#xD;
      hyperglycemia, oral glucose intolerance or markers of hyperglycemia such as HbA1c. However,&#xD;
      we now recognize that diabetes is a heterogeneous disorder. With the existing overly&#xD;
      simplistic diagnostic criteria, treatment failure rates are high for virtually every agent&#xD;
      currently in the drug arsenal - including insulin. In the late 1990's oncologists pioneered&#xD;
      the use of high-throughput molecular technologies, such as transcriptome profiling and more&#xD;
      recently metabolomics to identify discrete sub-classes of cancers that cannot be&#xD;
      distinguished histologically or by a small number of biochemical markers. That effort rapidly&#xD;
      accelerated the pace of scientific discovery and quickly led to the development of&#xD;
      personalized cancer therapeutics. We believe that those cancer efforts provide a roadmap for&#xD;
      biomarker discovery and personalized therapy in diabetes. molecular phenotyping (profiling&#xD;
      the metabolome, transcriptome, and epigenome) with advanced bioinformatics analysis will&#xD;
      identify discrete subtypes of diabetes - ushering in a new era of personalized diagnosis and&#xD;
      therapy in diabetes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2010</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Perform 'deep' clinical and molecular phenotyping of 360 adults- Diabetic and Non-Diabetic</measure>
    <time_frame>up to Day 9</time_frame>
    <description>Phenotyping will include whole body composition (DEXA), substrate metabolism, classic diabetes phenotypes, and detailed molecular phenotyping of circulating mononuclear cells/ plasma, muscle and adipose tissue.</description>
  </primary_outcome>
  <number_of_groups>8</number_of_groups>
  <enrollment type="Actual">80</enrollment>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Non-Diabetic Lean Athletes</arm_group_label>
    <description>Athletes with a Body Mass Index (BMI) less than or equal to 25 kg/m2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Diabetic Lean No Diabetes History</arm_group_label>
    <description>Adults with a BMI &lt; 25 kg/m2 and no family history of diabetes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Diabetic Lean Yes Diabetes History</arm_group_label>
    <description>Adults with a BMI &lt; 25 kg/m2 and family history of diabetes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Diabetic Obese</arm_group_label>
    <description>Adults with BMI greater than or equal to 30 kg/m2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Diabetic Obese Female PCOS</arm_group_label>
    <description>Female adults with BMI &gt; 30 kg/m2 and Polycystic Ovarian Syndrome (PCOS).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic No Medication</arm_group_label>
    <description>Have diabetes and currently receiving no medication or early treatment with one medication. Some participants receiving insulin may also be included in this study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic GAD Ab+</arm_group_label>
    <description>Have diabetes with Latent Autoimmune Diabetes in Adults (LADA).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic With NASH</arm_group_label>
    <description>Have diabetes with Nonalcoholic Steatohepatitis (NASH), which is chronic liver disease with fat in the liver, inflammation, and damage not associated with drinking alcohol.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood Urine Fat tissue Muscle Tissue&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Community sample&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18&#xD;
&#xD;
          -  HbA1C &lt; 8.0% *&#xD;
&#xD;
          -  You have not gained or lost more than 3 kg or 6.6 pounds in the last 8 weeks&#xD;
&#xD;
          -  You have not lost more than 10% of your heaviest body weight in your lifetime&#xD;
&#xD;
          -  BMI &lt; 25 kg/m2 or &gt; 30 kg/m2&#xD;
&#xD;
          -  Women: more than 1 year post-partum&#xD;
&#xD;
          -  Have diabetes and are able to maintain accurate and reliable home glucose monitoring&#xD;
             logs&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with more than 2 of the following: metformin (Fortamet, Glucophage,&#xD;
             Glumetza, Riomet), sulfonylureas (Glucotrol, Diabeta, Glynase, Micronase),&#xD;
             Glucagon-like peptide-1 analogs (Byetta) and/or Dipeptidyl peptidase IV inhibitors&#xD;
             (Januvia, Onglyza)&#xD;
&#xD;
          -  Treatment with long acting Glucagon-like peptide-1 agonists within the last 3 months&#xD;
             (i.e. exenatide once weekly)&#xD;
&#xD;
          -  Treatment with thiazolidinediones (TZDs) (i.e. Avandia, Actos, Rezulin) within the&#xD;
             last 3 months&#xD;
&#xD;
          -  Known, untreated thyroid disease or abnormal thyroid function blood test.*&#xD;
&#xD;
          -  Known diagnosis of liver disease (except NASH) or elevated liver function blood test&#xD;
&#xD;
          -  Known diagnosis of kidney disease or elevated kidney function blood test&#xD;
&#xD;
          -  Uncontrolled high blood pressure (BP &gt; 140 systolic or &gt; 90 diastolic)&#xD;
&#xD;
          -  Start of or changes in oral contraceptives or hormone replacement therapy within the&#xD;
             last 3 months&#xD;
&#xD;
          -  Use of drugs or alcohol (&gt; 3 drinks per day) within the last 5 years.&#xD;
&#xD;
          -  Uncontrolled psychiatric disease that would interfere with study participation.&#xD;
&#xD;
          -  History of cancer within the last 5 years (skin cancers, with the exception of&#xD;
             melanoma, may be acceptable)&#xD;
&#xD;
          -  History of organ transplant&#xD;
&#xD;
          -  History of heart attack within the last 6 months&#xD;
&#xD;
          -  Current treatment with blood thinners or antiplatelet medications that cannot be&#xD;
             safely stopped for testing procedures&#xD;
&#xD;
          -  Current anemia&#xD;
&#xD;
          -  History of HIV, active Hepatitis B or C, or Tuberculosis&#xD;
&#xD;
          -  Presence of clinically significant abnormalities on electrocardiogram.&#xD;
&#xD;
          -  Current smokers (smoking any nicotine or non-nicotine product within the past 3&#xD;
             months)&#xD;
&#xD;
          -  Use of any medications known to influence glucose, fat and/or energy metabolism within&#xD;
             the last 3 months (e.g., growth hormone therapy, glucocorticoids [steroids], etc.)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven R Smith, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Translational Research Institute for Metabolism and Diabetes</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Translational Research Institute for Metabolism and Diabetes</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.tri-md.org</url>
    <description>Florida Hospital Translational Research Institute for Metabolism and Diabetes</description>
  </link>
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    <citation>Shoelson SE, Lee J, Yuan M. Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord. 2003 Dec;27 Suppl 3:S49-52. doi: 10.1038/sj.ijo.0802501.</citation>
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    <citation>Moro C, Bajpeyi S, Smith SR. Determinants of intramyocellular triglyceride turnover: implications for insulin sensitivity. Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E203-13. doi: 10.1152/ajpendo.00624.2007. Epub 2007 Nov 14.</citation>
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    <citation>Ritov VB, Menshikova EV, Azuma K, Wood R, Toledo FG, Goodpaster BH, Ruderman NB, Kelley DE. Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity. Am J Physiol Endocrinol Metab. 2010 Jan;298(1):E49-58. doi: 10.1152/ajpendo.00317.2009. Epub 2009 Nov 3.</citation>
    <PMID>19887598</PMID>
  </reference>
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  <verification_date>February 2018</verification_date>
  <study_first_submitted>May 16, 2014</study_first_submitted>
  <study_first_submitted_qc>August 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <last_update_submitted>February 21, 2018</last_update_submitted>
  <last_update_submitted_qc>February 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_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/NCT02226640
org study id: TRIMDFH 238153
nct id: NCT02226640
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
This is a study to identify different subtypes of type 2 diabetes. The investigators will
      look for information at the molecular level, which may lead to personalized diagnosis and
      therapies.
Type 2 diabetes mellitus (T2DM) is approaching epidemic prevalence in the US adult population
      (over 1 in 10 of all US adults over 20). Diabetes is diagnosed based on fasting
      hyperglycemia, oral glucose intolerance or markers of hyperglycemia such as HbA1c. However,
      we now recognize that diabetes is a heterogeneous disorder. With the existing overly
      simplistic diagnostic criteria, treatment failure rates are high for virtually every agent
      currently in the drug arsenal - including insulin. In the late 1990's oncologists pioneered
      the use of high-throughput molecular technologies, such as transcriptome profiling and more
      recently metabolomics to identify discrete sub-classes of cancers that cannot be
      distinguished histologically or by a small number of biochemical markers. That effort rapidly
      accelerated the pace of scientific discovery and quickly led to the development of
      personalized cancer therapeutics. We believe that those cancer efforts provide a roadmap for
      biomarker discovery and personalized therapy in diabetes. molecular phenotyping (profiling
      the metabolome, transcriptome, and epigenome) with advanced bioinformatics analysis will
      identify discrete subtypes of diabetes - ushering in a new era of personalized diagnosis and
      therapy in diabetes.
observational model: Cohort
time perspective: Prospective
measure: Perform 'deep' clinical and molecular phenotyping of 360 adults- Diabetic and Non-Diabetic
time frame: up to Day 9
description: Phenotyping will include whole body composition (DEXA), substrate metabolism, classic diabetes phenotypes, and detailed molecular phenotyping of circulating mononuclear cells/ plasma, muscle and adipose tissue.
arm group label: Non-Diabetic Lean Athletes
description: Athletes with a Body Mass Index (BMI) less than or equal to 25 kg/m2.
arm group label: Non-Diabetic Lean No Diabetes History
description: Adults with a BMI < 25 kg/m2 and no family history of diabetes
arm group label: Non-Diabetic Lean Yes Diabetes History
description: Adults with a BMI < 25 kg/m2 and family history of diabetes
arm group label: Non-Diabetic Obese
description: Adults with BMI greater than or equal to 30 kg/m2.
arm group label: Non-Diabetic Obese Female PCOS
description: Female adults with BMI > 30 kg/m2 and Polycystic Ovarian Syndrome (PCOS).
arm group label: Diabetic No Medication
description: Have diabetes and currently receiving no medication or early treatment with one medication. Some participants receiving insulin may also be included in this study
arm group label: Diabetic GAD Ab+
description: Have diabetes with Latent Autoimmune Diabetes in Adults (LADA).
arm group label: Diabetic With NASH
description: Have diabetes with Nonalcoholic Steatohepatitis (NASH), which is chronic liver disease with fat in the liver, inflammation, and damage not associated with drinking alcohol.
Blood Urine Fat tissue Muscle Tissue
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Steven R Smith, MD
role: Principal Investigator
affiliation: Translational Research Institute for Metabolism and Diabetes
facility: 
country: United States
url: http://www.tri-md.org
description: Florida Hospital Translational Research Institute for Metabolism and Diabetes
citation: Shoelson SE, Lee J, Yuan M. Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord. 2003 Dec;27 Suppl 3:S49-52. doi: 10.1038/sj.ijo.0802501.
PMID: 14704745
citation: Reitman ML, Arioglu E, Gavrilova O, Taylor SI. Lipoatrophy revisited. Trends Endocrinol Metab. 2000 Dec;11(10):410-6. doi: 10.1016/s1043-2760(00)00309-x.
PMID: 11091118
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responsible party type: Sponsor
mesh term: Diabetes Mellitus