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/NCT05985135</url>
    </required_header>
    <id_info>
      <org_study_id>21-000001</org_study_id>
      <nct_id>NCT05985135</nct_id>
    </id_info>
    <brief_title>Impact of Insulin Deprivation and Hyperglycemia on Plasma Protein Synthesis in People With Type 1 Diabetes Mellitus</brief_title>
    <official_title>Impact of Insulin Deprivation and Hyperglycemia on Plasma Protein Synthesis in People With Type 1 Diabetes Mellitus and Diabetes After Total Pancreatectomy</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>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This research is being done to better understand how insulin effects muscle, blood, and the&#xD;
        body in people with Type 1 Diabetes.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Insulin's contribution in controlling glucose homeostasis has been well appreciated but, its&#xD;
        role in maintaining proteome homeostasis is less understood. Some animal and human studies&#xD;
        have demonstrated that insulin signaling regulates protein synthesis and degradation as well&#xD;
        as posttranslational modifications at the tissue level. Insulin's effect on the muscle's&#xD;
        mitochondrial proteo-stasis has also been elucidated. Insulin deprivation increases global&#xD;
        synthesis of splanchnic proteins based on isotope dilution studies across splanchnic bed.&#xD;
        Most plasma proteins are derived from liver and preliminary studies suggest that synthesis&#xD;
        rates of some plasma proteins increase while others decrease. Fractional rates of synthesis&#xD;
        of various plasma proteins from the liver have been demonstrated in insulin deprivation&#xD;
        state. These proteins might be implicated in the development of some of the complications&#xD;
        from diabetes mellitus type 1. (T1DM) especially of macrovascular. Researchers have recently&#xD;
        developed an isotope-based methodology to simultaneously measure in vivo synthesis rates of&#xD;
        multiple plasma proteins in human.&#xD;
  &#xD;
        In order to further investigate the effects of insulin deprivation researchers will apply the&#xD;
        novel non-radioactive stable isotope-based approach on the rate of different plasma protein&#xD;
        synthesis in T1DM and Diabetes after total pancreatectomy (DATP) in comparison with&#xD;
        non-diabetic controls. Researchers will study pancreatectomized people because like T1DM they&#xD;
        also are insulin deficient but unlike pancreatectomized people also are deficient in&#xD;
        glucagon. Some tantalizing data from many studies indicate that glucagon also have catabolic&#xD;
        effect not only on liver derived proteins but also on skeletal muscle-based proteins. Since&#xD;
        skeletal muscle has no glucagon receptors, researchers hypothesize that unknown factors are&#xD;
        released to the circulation that act on skeletal muscle to release amino acids for&#xD;
        consumption in liver. Researchers will measure amino metabolites, acyl carnitines, organic&#xD;
        acids, and ceramides in plasma and determine the blood exosome cargo by mass&#xD;
        spectrometry-proteins and lipids and miRNA by PCR.&#xD;
  &#xD;
        Researchers have previously shown reduced muscle mitochondrial ATP production during insulin&#xD;
        deprivation in both T1D humans and diabetic mice and here researchers will measure&#xD;
        mitochondrial energy dynamics in all study participants by the established techniques&#xD;
        available in our lab.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">August 2028</completion_date>
    <primary_completion_date type="Anticipated">August 2028</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>Parallel Assignment</intervention_model>
      <primary_purpose>Health Services Research</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Protein synthesis</measure>
      <time_frame>Approximately 7 hours</time_frame>
      <description>Measurement of isotope abundance in peptides derived from the digested proteins</description>
    </primary_outcome>
    <number_of_arms>6</number_of_arms>
    <enrollment type="Anticipated">70</enrollment>
    <condition>Type 1 Diabetes</condition>
    <arm_group>
      <arm_group_label>Type 1 Diabetes Mellitus (T1DM) Insulin Deprived</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will have their insulin infusions replaced with saline and have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Type 1 Diabetes Mellitus (T1DM) Insulin Treated</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will continue their baseline insulin infusion while maintaining a target blood glucose range. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will be continue their baseline insulin infusion for 2 hours and then receive an intravenous dextrose infusion to maintain elevated blood sugar levels. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Non-Diabetic Controls</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Subjects will have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Diabetes after Total Pancreatectomized (DATP) Insulin Treated</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will continue their baseline insulin infusion while maintaining a target blood glucose range. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Diabetes after Total Pancreatectomized (DATP) Insulin Deprived</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will have their insulin infusions replaced with saline and have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Muscle Biopsy</intervention_name>
      <description>Needle muscle biopsy of the outer thigh muscle</description>
      <arm_group_label>Diabetes after Total Pancreatectomized (DATP) Insulin Deprived</arm_group_label>
      <arm_group_label>Diabetes after Total Pancreatectomized (DATP) Insulin Treated</arm_group_label>
      <arm_group_label>Non-Diabetic Controls</arm_group_label>
      <arm_group_label>Type 1 Diabetes Mellitus (T1DM) Insulin Deprived</arm_group_label>
      <arm_group_label>Type 1 Diabetes Mellitus (T1DM) Insulin Treated</arm_group_label>
      <arm_group_label>Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Jell-O with Amino acids</intervention_name>
      <description>An amino acid mixture containing 13C6 Lysine isotope label</description>
      <arm_group_label>Diabetes after Total Pancreatectomized (DATP) Insulin Deprived</arm_group_label>
      <arm_group_label>Diabetes after Total Pancreatectomized (DATP) Insulin Treated</arm_group_label>
      <arm_group_label>Non-Diabetic Controls</arm_group_label>
      <arm_group_label>Type 1 Diabetes Mellitus (T1DM) Insulin Deprived</arm_group_label>
      <arm_group_label>Type 1 Diabetes Mellitus (T1DM) Insulin Treated</arm_group_label>
      <arm_group_label>Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Dextrose</intervention_name>
      <description>Intravenous form of sugar</description>
      <arm_group_label>Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria - Type 1 Diabetes Group:&#xD;
  &#xD;
          - Able to provide written consent.&#xD;
  &#xD;
          Exclusion Criteria - Type 1 Diabetes Group::&#xD;
  &#xD;
            -  BMI &lt; 20 or &gt; 32 kg/m^2.&#xD;
  &#xD;
            -  Celiac disease.&#xD;
  &#xD;
            -  Pregnancy.&#xD;
  &#xD;
            -  Smoking.&#xD;
  &#xD;
            -  Reported history of illicit substance use.&#xD;
  &#xD;
            -  History of active cardiovascular, cerebrovascular, or peripheral vascular disease.&#xD;
  &#xD;
            -  Active renal disease evidenced by estimated glomerular filtration rate (GFR) &lt; 50&#xD;
               mL/min/1.73 m^2.&#xD;
  &#xD;
            -  Severe peripheral or autonomic neuropathy.&#xD;
  &#xD;
            -  Dementia or any other neurologic disease.&#xD;
  &#xD;
            -  Uncontrolled psychiatric disease.&#xD;
  &#xD;
            -  Any learning disability.&#xD;
  &#xD;
            -  Anemia.&#xD;
  &#xD;
            -  Thyroid-stimulating hormone (TSH) ≥ 7 or TSH ≤ 7 and free T4 ≤ 0.9.&#xD;
  &#xD;
            -  Hemoglobin A1c &gt; 9.0%.&#xD;
  &#xD;
            -  Type 2 Diabetes Mellitus (T2DM), or impaired fasting glucose.&#xD;
  &#xD;
            -  Detectable C peptide.&#xD;
  &#xD;
          Inclusion Criteria - Control Group:&#xD;
  &#xD;
            -  Able to provide written consent.&#xD;
  &#xD;
            -  T1DM treated with continuous subcutaneous insulin infusion (CSII) or multiple daily&#xD;
               injections (MDI) (not Degludec).&#xD;
  &#xD;
          Exclusion Criteria - Control Group:&#xD;
  &#xD;
            -  BMI &lt; 20 or &gt; 32 kg/m^2.&#xD;
  &#xD;
            -  Celiac disease.&#xD;
  &#xD;
            -  Pregnancy.&#xD;
  &#xD;
            -  Smoking.&#xD;
  &#xD;
            -  Reported history of illicit substance use.&#xD;
  &#xD;
            -  History of active cardiovascular, cerebrovascular, or peripheral vascular disease.&#xD;
  &#xD;
            -  Active renal disease evidenced by estimated GFR &lt; 50 mL/min/1.73 m^2.&#xD;
  &#xD;
            -  Severe peripheral or autonomic neuropathy.&#xD;
  &#xD;
            -  Dementia or any other neurologic disease.&#xD;
  &#xD;
            -  Uncontrolled psychiatric disease.&#xD;
  &#xD;
            -  Any learning disability.&#xD;
  &#xD;
            -  Anemia.&#xD;
  &#xD;
            -  TSH ≥ 7 or TSH ≤ 7 and free T4 ≤ 0.9.&#xD;
  &#xD;
            -  T2DM, or impaired fasting glucose.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>K. Sreekumaran Nair, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Mayo Clinic</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Mark Pataky, PhD, MS</last_name>
      <phone>507-255-8115</phone>
      <email>pataky.mark@mayo.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Rose Decker</last_name>
      <phone>507-285-6770</phone>
      <email>bilderback.rose@mayo.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Mayo Clinic</name>
        <address>
          <city>Rochester</city>
          <state>Minnesota</state>
          <zip>55905</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Mark Pataky, PhD, MS</last_name>
        <phone>507-255-8115</phone>
        <email>pataky.mark@mayo.edu</email>
      </contact>
      <contact_backup>
        <last_name>Rose Decker</last_name>
        <phone>507-255-6770</phone>
        <email>bilderback.rose@mayo.edu</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://www.mayo.edu/research/clinical-trials</url>
      <description>Mayo Clinic Clinical Trials</description>
    </link>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 2, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Mayo Clinic</investigator_affiliation>
      <investigator_full_name>K. Sreekumaran Nair</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Continuous subcutaneous insulin infusion</keyword>
    <keyword>Multiple daily injections of insulin</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>Hyperglycemia</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/NCT05985135
  org study id: 21-000001
  nct id: NCT05985135
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This research is being done to better understand how insulin effects muscle, blood, and the
        body in people with Type 1 Diabetes.
  Insulin's contribution in controlling glucose homeostasis has been well appreciated but, its
        role in maintaining proteome homeostasis is less understood. Some animal and human studies
        have demonstrated that insulin signaling regulates protein synthesis and degradation as well
        as posttranslational modifications at the tissue level. Insulin's effect on the muscle's
        mitochondrial proteo-stasis has also been elucidated. Insulin deprivation increases global
        synthesis of splanchnic proteins based on isotope dilution studies across splanchnic bed.
        Most plasma proteins are derived from liver and preliminary studies suggest that synthesis
        rates of some plasma proteins increase while others decrease. Fractional rates of synthesis
        of various plasma proteins from the liver have been demonstrated in insulin deprivation
        state. These proteins might be implicated in the development of some of the complications
        from diabetes mellitus type 1. (T1DM) especially of macrovascular. Researchers have recently
        developed an isotope-based methodology to simultaneously measure in vivo synthesis rates of
        multiple plasma proteins in human.
  
        In order to further investigate the effects of insulin deprivation researchers will apply the
        novel non-radioactive stable isotope-based approach on the rate of different plasma protein
        synthesis in T1DM and Diabetes after total pancreatectomy (DATP) in comparison with
        non-diabetic controls. Researchers will study pancreatectomized people because like T1DM they
        also are insulin deficient but unlike pancreatectomized people also are deficient in
        glucagon. Some tantalizing data from many studies indicate that glucagon also have catabolic
        effect not only on liver derived proteins but also on skeletal muscle-based proteins. Since
        skeletal muscle has no glucagon receptors, researchers hypothesize that unknown factors are
        released to the circulation that act on skeletal muscle to release amino acids for
        consumption in liver. Researchers will measure amino metabolites, acyl carnitines, organic
        acids, and ceramides in plasma and determine the blood exosome cargo by mass
        spectrometry-proteins and lipids and miRNA by PCR.
  
        Researchers have previously shown reduced muscle mitochondrial ATP production during insulin
        deprivation in both T1D humans and diabetic mice and here researchers will measure
        mitochondrial energy dynamics in all study participants by the established techniques
        available in our lab.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Health Services Research
  masking: None (Open Label)
  measure: Protein synthesis
  time frame: Approximately 7 hours
  description: Measurement of isotope abundance in peptides derived from the digested proteins
  arm group label: Type 1 Diabetes Mellitus (T1DM) Insulin Deprived
  arm group type: Experimental
  description: Subjects will have their insulin infusions replaced with saline and have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.
  arm group label: Type 1 Diabetes Mellitus (T1DM) Insulin Treated
  arm group type: Experimental
  description: Subjects will continue their baseline insulin infusion while maintaining a target blood glucose range. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.
  arm group label: Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia
  arm group type: Experimental
  description: Subjects will be continue their baseline insulin infusion for 2 hours and then receive an intravenous dextrose infusion to maintain elevated blood sugar levels. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.
  arm group label: Non-Diabetic Controls
  arm group type: Other
  description: Subjects will have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.
  arm group label: Diabetes after Total Pancreatectomized (DATP) Insulin Treated
  arm group type: Experimental
  description: Subjects will continue their baseline insulin infusion while maintaining a target blood glucose range. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.
  arm group label: Diabetes after Total Pancreatectomized (DATP) Insulin Deprived
  arm group type: Experimental
  description: Subjects will have their insulin infusions replaced with saline and have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.
  intervention type: Procedure
  intervention name: Muscle Biopsy
  description: Needle muscle biopsy of the outer thigh muscle
  arm group label: Diabetes after Total Pancreatectomized (DATP) Insulin Deprived
  arm group label: Diabetes after Total Pancreatectomized (DATP) Insulin Treated
  arm group label: Non-Diabetic Controls
  arm group label: Type 1 Diabetes Mellitus (T1DM) Insulin Deprived
  arm group label: Type 1 Diabetes Mellitus (T1DM) Insulin Treated
  arm group label: Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia
  intervention type: Other
  intervention name: Jell-O with Amino acids
  description: An amino acid mixture containing 13C6 Lysine isotope label
  arm group label: Diabetes after Total Pancreatectomized (DATP) Insulin Deprived
  arm group label: Diabetes after Total Pancreatectomized (DATP) Insulin Treated
  arm group label: Non-Diabetic Controls
  arm group label: Type 1 Diabetes Mellitus (T1DM) Insulin Deprived
  arm group label: Type 1 Diabetes Mellitus (T1DM) Insulin Treated
  arm group label: Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia
  intervention type: Dietary Supplement
  intervention name: Dextrose
  description: Intravenous form of sugar
  arm group label: Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: K. Sreekumaran Nair, MD
  role: Principal Investigator
  affiliation: Mayo Clinic
  last name: Mark Pataky, PhD, MS
  phone: 507-255-8115
  email: pataky.mark@mayo.edu
  last name: Rose Decker
  phone: 507-285-6770
  email: bilderback.rose@mayo.edu
  facility: 
  contact: 
  contact backup: 
  country: United States
  url: https://www.mayo.edu/research/clinical-trials
  description: Mayo Clinic Clinical Trials
  responsible party type: Principal Investigator
  investigator affiliation: Mayo Clinic
  investigator full name: K. Sreekumaran Nair
  investigator title: Principal Investigator
  mesh term: Diabetes Mellitus
  mesh term: Diabetes Mellitus, Type 1
  mesh term: Hyperglycemia
  sharing ipd: No