<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/NCT01726491</url>
  </required_header>
  <id_info>
    <org_study_id>11-007028</org_study_id>
    <nct_id>NCT01726491</nct_id>
  </id_info>
  <brief_title>Epigenetics and the Origin of Muscle Insulin Resistance in Humans</brief_title>
  <official_title>Epigenetics and the Origin of Muscle Insulin Resistance in Humans</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are trying to understand the role of DNA (deoxyribonucleic acid)&#xD;
      methylation in insulin resistance in skeletal muscle and blood tissues. DNA methylation is a&#xD;
      normal chemical process in the body that modifies DNA. By studying this, the investigators&#xD;
      hope to better understand the causes of insulin resistance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Insulin resistance is defined as the decreased ability of insulin to perform its biological&#xD;
      function in the muscle, liver and fat. Genetic and environmental factors are known to&#xD;
      influence insulin sensitivity. It is not known how this is mediated. This study looks at the&#xD;
      role of epigenetics (modifications of proteins associated with DNA and methylation of DNA) in&#xD;
      alterations in insulin resistance. We will study lean healthy people, obese non-diabetic&#xD;
      people and people with type 2 diabetes to characterize the DNA methylation patterns in muscle&#xD;
      in each group. The second aim of the study is to see how a single bout of exercise affects&#xD;
      the DNA methylation in the muscle. The third aim looks at the effect of 8 weeks of supervised&#xD;
      exercise on the DNA methylation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">November 21, 2016</completion_date>
  <primary_completion_date type="Actual">November 21, 2016</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>DNA methylation of genes in insulin resistance</measure>
    <time_frame>Baseline to visit 33 (approx 2 months)</time_frame>
    <description>DNA methylation of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeleton proteins in insulin resistance, with an acute episode of exercise, and with eight weeks of training exercise.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>mRNA expression of genes</measure>
    <time_frame>Baseline to visit 33 approx 2 months</time_frame>
    <description>mRNA expression of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeletal signaling are altered in insulin resistance, with an acute episode of exercise and with 8 weeks of exercise training.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">46</enrollment>
  <condition>Diabetes Mellitus Type 2 in Obese</condition>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Insulin resistance epigenetics</arm_group_label>
    <description>This experiment will use the Infinium methylation assay to perform epigenome mapping and define patterns of DNA methylation in skeletal muscle and whole blood tissue of metabolically well-characterized lean healthy, obese nondiabetic, and type 2 diabetic volunteers. We will test the hypotheses that&#xD;
(1) There is an increased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation and altered methylation of promoters of genes coding for extracellular matrix and cytoskeletal proteins in insulin resistance, (2) The altered methylation patterns observed correspond to protein and mRNA expression changes, and (3) There are coordinated patterns of DNA methylation between the skeletal muscle and whole blood tissues in insulin resistance.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single bout of exercise</arm_group_label>
    <description>This experiment will test the hypotheses in lean healthy, obese non-diabetic and type 2 diabetic volunteers that&#xD;
Increased methylation of the PGC-1α promoter predicts a decreased response of this gene to a single bout of exercise, and&#xD;
Altered methylation of promoters of nuclear encoded mitochondrial genes predicts a decreased response of this gene to a single bout of exercise.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Eight weeks of exercise</arm_group_label>
    <description>This experiment will test the hypothesis in lean healthy, obese non-diabetic and type 2 diabetic volunteers that&#xD;
There is decreased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation, and the altered methylation corresponds to protein and mRNA (messenger ribonucleic acid) expression changes,&#xD;
There is altered methylation of genes involved in inflammation and cytoskeletal structure.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      thigh muscle biopsies bloodsamples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Three groups of volunteers will be studied: 1) lean, healthy volunteers, 2)obese volunteers&#xD;
        without type 2 diabetes, and 3) volunteers with type 2 diabetes.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Volunteers must be:&#xD;
&#xD;
          -  21 - 55 years old&#xD;
&#xD;
          -  must be non-lactating, non-pregnant&#xD;
&#xD;
          -  not taking medications known to affect glucose or if taking them, on stable doses.&#xD;
&#xD;
          -  free of significant heart or lung disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lori Roust, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dawn K Coletta, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>January 11, 2018</last_update_submitted>
  <last_update_submitted_qc>January 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 16, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Lori R. Roust</investigator_full_name>
    <investigator_title>Consultant in Endocrinology</investigator_title>
  </responsible_party>
  <keyword>Insulin resistance</keyword>
  <keyword>Exercise</keyword>
  <keyword>Type 2 diabetes mellitus</keyword>
  <keyword>Obesity</keyword>
  <keyword>Epigenetic studies</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</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/NCT01726491
org study id: 11-007028
nct id: NCT01726491
lead sponsor: 
has dmc: No
The investigators are trying to understand the role of DNA (deoxyribonucleic acid)
      methylation in insulin resistance in skeletal muscle and blood tissues. DNA methylation is a
      normal chemical process in the body that modifies DNA. By studying this, the investigators
      hope to better understand the causes of insulin resistance.
Insulin resistance is defined as the decreased ability of insulin to perform its biological
      function in the muscle, liver and fat. Genetic and environmental factors are known to
      influence insulin sensitivity. It is not known how this is mediated. This study looks at the
      role of epigenetics (modifications of proteins associated with DNA and methylation of DNA) in
      alterations in insulin resistance. We will study lean healthy people, obese non-diabetic
      people and people with type 2 diabetes to characterize the DNA methylation patterns in muscle
      in each group. The second aim of the study is to see how a single bout of exercise affects
      the DNA methylation in the muscle. The third aim looks at the effect of 8 weeks of supervised
      exercise on the DNA methylation.
observational model: Cohort
time perspective: Prospective
measure: DNA methylation of genes in insulin resistance
time frame: Baseline to visit 33 (approx 2 months)
description: DNA methylation of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeleton proteins in insulin resistance, with an acute episode of exercise, and with eight weeks of training exercise.
measure: mRNA expression of genes
time frame: Baseline to visit 33 approx 2 months
description: mRNA expression of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeletal signaling are altered in insulin resistance, with an acute episode of exercise and with 8 weeks of exercise training.
arm group label: Insulin resistance epigenetics
description: This experiment will use the Infinium methylation assay to perform epigenome mapping and define patterns of DNA methylation in skeletal muscle and whole blood tissue of metabolically well-characterized lean healthy, obese nondiabetic, and type 2 diabetic volunteers. We will test the hypotheses that
(1) There is an increased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation and altered methylation of promoters of genes coding for extracellular matrix and cytoskeletal proteins in insulin resistance, (2) The altered methylation patterns observed correspond to protein and mRNA expression changes, and (3) There are coordinated patterns of DNA methylation between the skeletal muscle and whole blood tissues in insulin resistance.
arm group label: Single bout of exercise
description: This experiment will test the hypotheses in lean healthy, obese non-diabetic and type 2 diabetic volunteers that
Increased methylation of the PGC-1α promoter predicts a decreased response of this gene to a single bout of exercise, and
Altered methylation of promoters of nuclear encoded mitochondrial genes predicts a decreased response of this gene to a single bout of exercise.
arm group label: Eight weeks of exercise
description: This experiment will test the hypothesis in lean healthy, obese non-diabetic and type 2 diabetic volunteers that
There is decreased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation, and the altered methylation corresponds to protein and mRNA (messenger ribonucleic acid) expression changes,
There is altered methylation of genes involved in inflammation and cytoskeletal structure.
thigh muscle biopsies bloodsamples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Lori Roust, MD
role: Principal Investigator
affiliation: Mayo Clinic
last name: Dawn K Coletta, Ph.D.
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Lori R. Roust
investigator title: Consultant in Endocrinology
mesh term: Diabetes Mellitus
mesh term: Insulin Resistance
mesh term: Diabetes Mellitus, Type 2