xml: <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/NCT05973799</url>
    </required_header>
    <id_info>
      <org_study_id>2019-0816</org_study_id>
      <nct_id>NCT05973799</nct_id>
    </id_info>
    <brief_title>Effect of Fasting on Hypoglycemic Counterregulation in Type 1 Diabetes</brief_title>
    <official_title>Effect of Fasting on Hypoglycemic Counterregulation in Type 1 Diabetes</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Cincinnati</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Cincinnati</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Iatrogenic hypoglycemia is still considered to be the number one barrier to effective&#xD;
        glycemic control in patients with type 1 diabetes (T1D). In a previous study, it was observed&#xD;
        in people without diabetes that fasting can be detrimental to the hormonal and hepatic&#xD;
        responses to insulin-induced hypoglycemia. In the experiments described herein, the impact&#xD;
        fasting has on hypoglycemic counterregulation in people with T1D will be determined.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Because patients with type 1 diabetes (T1D) are required to estimate and administer their own&#xD;
        insulin requirements, they frequently overestimate their needs. This often leads to&#xD;
        debilitating insulin-induced hypoglycemia, which is the number one barrier to the safe,&#xD;
        effective management of glycemia in this population. In addition to the difficulty estimating&#xD;
        one's own insulin requirements after a meal, counterregulatory hormone responses to&#xD;
        hypoglycemia are impaired in patients with T1D, thereby reducing hepatic glucose production&#xD;
        (HGP) and increasing the depth and duration of the hypoglycemic episode.&#xD;
  &#xD;
        The discovery of ways by which counterregulatory responses to hypoglycemia can be improved in&#xD;
        people with T1D is a priority. In previous experiments, it was observed that fasting reduces&#xD;
        counterregulatory hormone secretion in healthy humans during insulin-induced hypoglycemia,&#xD;
        thereby reducing hepatic glucose production (HGP). Therefore, the studies proposed herein&#xD;
        will determine the effect of fasting on hypoglycemic counterregulation in people with T1D. It&#xD;
        is hypothesized that fasting will diminish the hormonal and hepatic responses to&#xD;
        insulin-induced hypoglycemia.&#xD;
  &#xD;
        Each subject will undergo two trials; one where they eat an isocaloric breakfast and lunch&#xD;
        prior to an insulin-induced hypoglycemic challenge and a second one during which they remain&#xD;
        fasted prior to the hypoglycemic challenge. This study design will allow assessment of the&#xD;
        relationship between fasting and the counterregulatory responses to insulin-induced&#xD;
        hypoglycemia in a population that is particularly vulnerable to low blood sugar.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">October 10, 2019</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <intervention_model_description>Each subject will undergo two metabolic studies, one after having remained fasted and one after having eaten breakfast and lunch.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Glucagon</measure>
      <time_frame>During procedure, up to 2.5 hours</time_frame>
      <description>From plasma</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Hepatic glucose production</measure>
      <time_frame>During procedure, up to 2.5 hours</time_frame>
      <description>From plasma</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Glucose infusion rate</measure>
      <time_frame>During procedure, up to 2.5 hours</time_frame>
      <description>Amount of glucose required to maintain glycemia at ~55 mg/dL.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Epinephrine</measure>
      <time_frame>During procedure, up to 2.5 hours</time_frame>
      <description>From plasma</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Peripheral glucose uptake</measure>
      <time_frame>During procedure, up to 2.5 hours</time_frame>
      <description>From plasma</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Cortisol</measure>
      <time_frame>During procedure, up to 2.5 hours</time_frame>
      <description>From plasma</description>
    </other_outcome>
    <other_outcome>
      <measure>Growth Hormone</measure>
      <time_frame>During procedure, up to 2.5 hours</time_frame>
      <description>From plasma</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">10</enrollment>
    <condition>Hypoglycemia</condition>
    <condition>type1diabetes</condition>
    <arm_group>
      <arm_group_label>Fasting</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will remain fasted prior to insulin-induced hypoglycemia.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Feeding</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Fasting</intervention_name>
      <description>Subjects remain fasted prior to insulin-induced hypoglycemia.</description>
      <arm_group_label>Fasting</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Feeding</intervention_name>
      <description>Subjects eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.</description>
      <arm_group_label>Feeding</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  males and females of any race or ethnicity&#xD;
  &#xD;
            -  non-obese (BMI &lt; or = to 30)&#xD;
  &#xD;
            -  have a diagnosis of type 1 diabetes&#xD;
  &#xD;
            -  C-peptide negative&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  pregnant women&#xD;
  &#xD;
            -  cigarette smoking&#xD;
  &#xD;
            -  Taking inflammation-targeting steroids (e.g., prednisone).&#xD;
  &#xD;
            -  Taking medications targeting adrenergic signaling (e.g., beta-blockers,&#xD;
               bronchodilators).&#xD;
  &#xD;
            -  Hematocrit less than 33%.&#xD;
  &#xD;
            -  Presence of HIV or hepatitis (due to their deleterious effects on the liver).&#xD;
  &#xD;
            -  The presence of cardiovascular or peripheral vascular disease.&#xD;
  &#xD;
            -  The presence of neuropathy, retinopathy or nephropathy.&#xD;
  &#xD;
            -  A detection of the presence of any other disease or condition by one of the study&#xD;
               doctors, that would be expected to confound the responses to insulin-induced&#xD;
               hypoglycemia or make participation in the study dangerous to the individual.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Jason Winnick, PhD</last_name>
      <phone>513-558-4437</phone>
      <email>jason.winnick@uc.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Alyssa Randolph</last_name>
      <phone>513-558-3427</phone>
      <email>Randolas@ucmail.uc.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of Cincinnati</name>
        <address>
          <city>Cincinnati</city>
          <state>Ohio</state>
          <zip>45267-0547</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jason Winnick, PhD</last_name>
        <phone>513-558-4437</phone>
        <email>jason.winnick@uc.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 12, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>August 2, 2023</last_update_submitted>
    <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Cincinnati</investigator_affiliation>
      <investigator_full_name>Jason Winnick</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>glucagon</keyword>
    <keyword>hepatic glucose metabolism</keyword>
    <keyword>liver glycogen</keyword>
    <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>
      <mesh_term>Hypoglycemia</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05973799
  org study id: 2019-0816
  nct id: NCT05973799
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Iatrogenic hypoglycemia is still considered to be the number one barrier to effective
        glycemic control in patients with type 1 diabetes (T1D). In a previous study, it was observed
        in people without diabetes that fasting can be detrimental to the hormonal and hepatic
        responses to insulin-induced hypoglycemia. In the experiments described herein, the impact
        fasting has on hypoglycemic counterregulation in people with T1D will be determined.
  Because patients with type 1 diabetes (T1D) are required to estimate and administer their own
        insulin requirements, they frequently overestimate their needs. This often leads to
        debilitating insulin-induced hypoglycemia, which is the number one barrier to the safe,
        effective management of glycemia in this population. In addition to the difficulty estimating
        one's own insulin requirements after a meal, counterregulatory hormone responses to
        hypoglycemia are impaired in patients with T1D, thereby reducing hepatic glucose production
        (HGP) and increasing the depth and duration of the hypoglycemic episode.
  
        The discovery of ways by which counterregulatory responses to hypoglycemia can be improved in
        people with T1D is a priority. In previous experiments, it was observed that fasting reduces
        counterregulatory hormone secretion in healthy humans during insulin-induced hypoglycemia,
        thereby reducing hepatic glucose production (HGP). Therefore, the studies proposed herein
        will determine the effect of fasting on hypoglycemic counterregulation in people with T1D. It
        is hypothesized that fasting will diminish the hormonal and hepatic responses to
        insulin-induced hypoglycemia.
  
        Each subject will undergo two trials; one where they eat an isocaloric breakfast and lunch
        prior to an insulin-induced hypoglycemic challenge and a second one during which they remain
        fasted prior to the hypoglycemic challenge. This study design will allow assessment of the
        relationship between fasting and the counterregulatory responses to insulin-induced
        hypoglycemia in a population that is particularly vulnerable to low blood sugar.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: Each subject will undergo two metabolic studies, one after having remained fasted and one after having eaten breakfast and lunch.
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Glucagon
  time frame: During procedure, up to 2.5 hours
  description: From plasma
  measure: Hepatic glucose production
  time frame: During procedure, up to 2.5 hours
  description: From plasma
  measure: Glucose infusion rate
  time frame: During procedure, up to 2.5 hours
  description: Amount of glucose required to maintain glycemia at ~55 mg/dL.
  measure: Epinephrine
  time frame: During procedure, up to 2.5 hours
  description: From plasma
  measure: Peripheral glucose uptake
  time frame: During procedure, up to 2.5 hours
  description: From plasma
  measure: Cortisol
  time frame: During procedure, up to 2.5 hours
  description: From plasma
  measure: Growth Hormone
  time frame: During procedure, up to 2.5 hours
  description: From plasma
  arm group label: Fasting
  arm group type: Experimental
  description: Subjects will remain fasted prior to insulin-induced hypoglycemia.
  arm group label: Feeding
  arm group type: Experimental
  description: Subjects will eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.
  intervention type: Other
  intervention name: Fasting
  description: Subjects remain fasted prior to insulin-induced hypoglycemia.
  arm group label: Fasting
  intervention type: Other
  intervention name: Feeding
  description: Subjects eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.
  arm group label: Feeding
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: No
  last name: Jason Winnick, PhD
  phone: 513-558-4437
  email: jason.winnick@uc.edu
  last name: Alyssa Randolph
  phone: 513-558-3427
  email: Randolas@ucmail.uc.edu
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of Cincinnati
  investigator full name: Jason Winnick
  investigator title: Principal Investigator
  mesh term: Diabetes Mellitus
  mesh term: Diabetes Mellitus, Type 1
  mesh term: Hypoglycemia
  sharing ipd: No