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/NCT05990933</url>
    </required_header>
    <id_info>
      <org_study_id>114664</org_study_id>
      <nct_id>NCT05990933</nct_id>
    </id_info>
    <brief_title>Role of Adrenaline in in the Inflammatory Response in Diabetes</brief_title>
    <acronym>RAID</acronym>
    <official_title>Role of Adrenaline in the Inflammatory Response in People With Diabetes Mellitus Type 1, and Healthy Individuals</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Cees Tack</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Radboud University Medical Center</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>
        The primary aim of the present study is to study the effect of adrenaline administration on&#xD;
        inflammatory parameters (e.g. leukocyte phenotype, cytokines, inflammatory proteins).&#xD;
        Secondary objectives consist of the effect of adrenaline on atherogenic parameters.&#xD;
  &#xD;
          -  All participants will receive intravenous infusion of adrenaline for an hour&#xD;
  &#xD;
          -  We will draw blood at 7 time points, not including screening&#xD;
  &#xD;
          -  Participants will be asked to return for a total of 4 times&#xD;
  &#xD;
        Researchers will compare 2 groups, healthy individuals versus people with diabetes type 1 to&#xD;
        see if the inflammatory reaction to adrenaline differs between these two groups.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Objective: The primary aim of the present study is to study the effect of adrenaline&#xD;
        administration on inflammatory parameters (e.g. leukocyte phenotype, cytokines, inflammatory&#xD;
        proteins). Secondary objectives consist of the effect of adrenaline on atherogenic&#xD;
        parameters.&#xD;
  &#xD;
        Potentially eligible adult ( 16 - 75 years) participants will be recruited from the diabetes&#xD;
        clinic at the department of internal medicine from the Radboud University Medical Center.&#xD;
        Healthy participants will be recruited through social media and other advertisements.&#xD;
        Researchers will recruit a total of 30 individuals, i.e. 15 healthy participants and 15&#xD;
        people with type 1 diabetes. Participants with type 1 diabetes will be equipped with a&#xD;
        blinded continuous glucose monitoring device (CGM) during the test, which will measure&#xD;
        interstitial glucose levels for a total of 10 days.&#xD;
  &#xD;
        Intervention: All participants will receive intravenous infusion of adrenaline at a rate of&#xD;
        0.04ug/kg/min for 1 hour. We will draw blood at baseline, 30 minutes, 60 minutes, 180&#xD;
        minutes, 24 hours 72 hours and a week after start of infusion. The blood samples will be used&#xD;
        for phenotyping of the innate immune system and measuring inflammatory and atherogenic&#xD;
        parameters. Throughout the infusion, vital parameters will be monitored.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">October 2024</completion_date>
    <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>All participants will receive intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour. We will draw blood at baseline, 30 minutes, 60 minutes, 180 minutes, 24 hours 72 and a week after start of infusion. These samples will be used for phenotyping of the innate immune system and measuring inflammatory and atherogenic parameters. Throughout the infusion vital parameters will be monitored.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Monocyte count</measure>
      <time_frame>Change from baseline compared to after 1 hour</time_frame>
      <description>The amount of monocytes following 60 minutes of adrenaline infusion compared to baseline to asses the adrenaline effect on the inflammatory response.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Leukocyte count</measure>
      <time_frame>Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion</time_frame>
      <description>Measurement of the amount of leukocytes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Leukocyte phenotype</measure>
      <time_frame>Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion</time_frame>
      <description>Measuring several phenotypes by using a pre-defined panel of interest with flow-cytometry ( e.g. NK-cells, granulocytes)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pro-inflammatory proteins</measure>
      <time_frame>Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion</time_frame>
      <description>Pro-inflammatory proteins using Olink Proteomics AB inflammation panel with 92 circulating inflammatory proteins ( e.g. EN-rage, FIT3L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Inflammation plasma parameters</measure>
      <time_frame>Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion</time_frame>
      <description>Inflammatory plasma protein using ELISA, ( e.g high sensitive-crp)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Atherogenic parameters</measure>
      <time_frame>Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion</time_frame>
      <description>Atherogenic parameters using ELISA method including but not limited to, VCAM-1, ICAM-1, E-Selectin, P-selectin, PAI-1, Plasma Endothelin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Insulin</measure>
      <time_frame>Change from baseline at, 60 and 180 minutes</time_frame>
      <description>Plasma levels of insulin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adrenaline</measure>
      <time_frame>Change from baseline at 30, 60 and 180 minutes</time_frame>
      <description>Plasma levels of adrenaline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Noradrenaline</measure>
      <time_frame>Change from baseline at 30, 60 and 180 minutes</time_frame>
      <description>Plasma levels of noradrenaline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Glucose variability</measure>
      <time_frame>2 weeks</time_frame>
      <description>Glucose variability measured by the blinded continuous glucose monitor including but not limited to, measuring time within range, amount of hypoglycaemic events, amount of hyperglycaemic events.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ex vivo cytokines</measure>
      <time_frame>Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion</time_frame>
      <description>Ex vivo production of pro- and anti-inflammatory cytokines and chemokines after ex vivo stimulation of isolated monocytes, including TNF-α, IL-6, IL-10 and IL-1β.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Distribution of monocyte subset</measure>
      <time_frame>Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion</time_frame>
      <description>Distribution of pro- and anti-inflammatory monocyte subsets using FACS (Fluorescence-activated Cell Sorting)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Inflammatory Response</condition>
    <condition>Diabetes type1</condition>
    <condition>Hypoglycemia</condition>
    <arm_group>
      <arm_group_label>People with type 1 diabetes</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The participants with type 1 diabetes will receive an intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Healthy individuals</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>The participants without type 1 diabetes will receive an intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Adrenaline</intervention_name>
      <description>Adrenaline infusion at a rate of 0.04ug/kg/min for 1 hour administered intravenously.</description>
      <arm_group_label>Healthy individuals</arm_group_label>
      <arm_group_label>People with type 1 diabetes</arm_group_label>
      <other_name>Adrenaline infusion</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Overall inclusion criteria:&#xD;
  &#xD;
            -  Ability to provide written informed consent&#xD;
  &#xD;
            -  Body-Mass Index: 19-30kg/m2&#xD;
  &#xD;
            -  Age ≥16 years, ≤ 75 years&#xD;
  &#xD;
            -  Blood pressure: &lt;140/90 mmHg&#xD;
  &#xD;
            -  Non-smoking&#xD;
  &#xD;
            -  Electrocardiogram not showing any serious arrythmia's (PVC's and PAC's accepted)&#xD;
  &#xD;
          Diabetes group specific criteria:&#xD;
  &#xD;
            -  Insulin treatment according to basal-bolus insulin regimen (injections or insulin&#xD;
               pump)&#xD;
  &#xD;
            -  Duration of diabetes &gt; 1 year&#xD;
  &#xD;
            -  HbA1c &lt; 100 mmol/mol,&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  - Any event of cardiovascular disease in the past 5 years (e.g. myocardial infarction,&#xD;
               stroke, heart failure, symptomatic peripheral arterial disease)&#xD;
  &#xD;
            -  Pregnancy or breastfeeding or unwillingness to undertake measures for birth control&#xD;
  &#xD;
            -  Epilepsy,&#xD;
  &#xD;
            -  Current treatment with Alpha or beta blockers ( doxazosin, propranolol)&#xD;
  &#xD;
            -  History of panic disorders&#xD;
  &#xD;
            -  History of Arrhythmias&#xD;
  &#xD;
            -  Use of immune-modifying drugs or antibiotics&#xD;
  &#xD;
            -  Use of tricyclic antidepressants or MAO inhibitors&#xD;
  &#xD;
            -  Use of statins (e.g. stop statins &gt;2 weeks before performing blood sampling.&#xD;
  &#xD;
            -  Any infection with systemic symptoms in past 2 weeks&#xD;
  &#xD;
            -  Previous vaccination in the past 2 weeks&#xD;
  &#xD;
            -  Proliferative retinopathy&#xD;
  &#xD;
            -  Nephropathy with an estimated glomerular filtration rate (by MDRD) ˂60ml/min/1.73m2&#xD;
  &#xD;
            -  Overt impaired hypoglycaemic awareness assed by the Clarke Questionnaire 4 or higher&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>16 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Cees Tack, MD. PHD.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Radboud University Medical Center (Radboudumc)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ilyas Mustafajev, MD</last_name>
      <phone>+31683358037</phone>
      <email>ilyas.mustafajev@radboudumc.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Rick Meijer, MD. PHD</last_name>
      <email>rick.meijer@radboudumc.nl</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Radboud UMC</name>
        <address>
          <city>Nijmegen</city>
          <state>Gelderland</state>
          <zip>6525GA</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <contact>
        <last_name>Ilyas Mustafajev, MD</last_name>
        <phone>+31683358037</phone>
        <email>ilyas.mustafajev@radboudumc.nl</email>
      </contact>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 2, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Radboud University Medical Center</investigator_affiliation>
      <investigator_full_name>Cees Tack</investigator_full_name>
      <investigator_title>Prof. Dr.</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>Hypoglycemia</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>Epinephrine</mesh_term>
      <mesh_term>Racepinephrine</mesh_term>
      <mesh_term>Epinephryl borate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>WE will share the study protocol using a data respository accesible through the research team on demand. Starting around 6 months after publication.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_time_frame>6 months after publication</ipd_time_frame>
      <ipd_access_criteria>The coordinating researcher will review acces requests. Seeing as the data are all anonimised acces will be granted for additional research in the field of inflammation or diabetes.</ipd_access_criteria>
    </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/NCT05990933
  org study id: 114664
  nct id: NCT05990933
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The primary aim of the present study is to study the effect of adrenaline administration on
        inflammatory parameters (e.g. leukocyte phenotype, cytokines, inflammatory proteins).
        Secondary objectives consist of the effect of adrenaline on atherogenic parameters.
  
          -  All participants will receive intravenous infusion of adrenaline for an hour
  
          -  We will draw blood at 7 time points, not including screening
  
          -  Participants will be asked to return for a total of 4 times
  
        Researchers will compare 2 groups, healthy individuals versus people with diabetes type 1 to
        see if the inflammatory reaction to adrenaline differs between these two groups.
  Objective: The primary aim of the present study is to study the effect of adrenaline
        administration on inflammatory parameters (e.g. leukocyte phenotype, cytokines, inflammatory
        proteins). Secondary objectives consist of the effect of adrenaline on atherogenic
        parameters.
  
        Potentially eligible adult ( 16 - 75 years) participants will be recruited from the diabetes
        clinic at the department of internal medicine from the Radboud University Medical Center.
        Healthy participants will be recruited through social media and other advertisements.
        Researchers will recruit a total of 30 individuals, i.e. 15 healthy participants and 15
        people with type 1 diabetes. Participants with type 1 diabetes will be equipped with a
        blinded continuous glucose monitoring device (CGM) during the test, which will measure
        interstitial glucose levels for a total of 10 days.
  
        Intervention: All participants will receive intravenous infusion of adrenaline at a rate of
        0.04ug/kg/min for 1 hour. We will draw blood at baseline, 30 minutes, 60 minutes, 180
        minutes, 24 hours 72 hours and a week after start of infusion. The blood samples will be used
        for phenotyping of the innate immune system and measuring inflammatory and atherogenic
        parameters. Throughout the infusion, vital parameters will be monitored.
  allocation: Non-Randomized
  intervention model: Single Group Assignment
  intervention model description: All participants will receive intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour. We will draw blood at baseline, 30 minutes, 60 minutes, 180 minutes, 24 hours 72 and a week after start of infusion. These samples will be used for phenotyping of the innate immune system and measuring inflammatory and atherogenic parameters. Throughout the infusion vital parameters will be monitored.
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Monocyte count
  time frame: Change from baseline compared to after 1 hour
  description: The amount of monocytes following 60 minutes of adrenaline infusion compared to baseline to asses the adrenaline effect on the inflammatory response.
  measure: Leukocyte count
  time frame: Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion
  description: Measurement of the amount of leukocytes
  measure: Leukocyte phenotype
  time frame: Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion
  description: Measuring several phenotypes by using a pre-defined panel of interest with flow-cytometry ( e.g. NK-cells, granulocytes)
  measure: Pro-inflammatory proteins
  time frame: Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion
  description: Pro-inflammatory proteins using Olink Proteomics AB inflammation panel with 92 circulating inflammatory proteins ( e.g. EN-rage, FIT3L)
  measure: Inflammation plasma parameters
  time frame: Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion
  description: Inflammatory plasma protein using ELISA, ( e.g high sensitive-crp)
  measure: Atherogenic parameters
  time frame: Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion
  description: Atherogenic parameters using ELISA method including but not limited to, VCAM-1, ICAM-1, E-Selectin, P-selectin, PAI-1, Plasma Endothelin
  measure: Insulin
  time frame: Change from baseline at, 60 and 180 minutes
  description: Plasma levels of insulin
  measure: Adrenaline
  time frame: Change from baseline at 30, 60 and 180 minutes
  description: Plasma levels of adrenaline
  measure: Noradrenaline
  time frame: Change from baseline at 30, 60 and 180 minutes
  description: Plasma levels of noradrenaline
  measure: Glucose variability
  time frame: 2 weeks
  description: Glucose variability measured by the blinded continuous glucose monitor including but not limited to, measuring time within range, amount of hypoglycaemic events, amount of hyperglycaemic events.
  measure: Ex vivo cytokines
  time frame: Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion
  description: Ex vivo production of pro- and anti-inflammatory cytokines and chemokines after ex vivo stimulation of isolated monocytes, including TNF-α, IL-6, IL-10 and IL-1β.
  measure: Distribution of monocyte subset
  time frame: Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion
  description: Distribution of pro- and anti-inflammatory monocyte subsets using FACS (Fluorescence-activated Cell Sorting)
  arm group label: People with type 1 diabetes
  arm group type: Experimental
  description: The participants with type 1 diabetes will receive an intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour.
  arm group label: Healthy individuals
  arm group type: Active Comparator
  description: The participants without type 1 diabetes will receive an intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour.
  intervention type: Drug
  intervention name: Adrenaline
  description: Adrenaline infusion at a rate of 0.04ug/kg/min for 1 hour administered intravenously.
  arm group label: Healthy individuals
  arm group label: People with type 1 diabetes
  other name: Adrenaline infusion
  criteria: 
  gender: All
  minimum age: 16 Years
  maximum age: 75 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Cees Tack, MD. PHD.
  role: Principal Investigator
  affiliation: Radboud University Medical Center (Radboudumc)
  last name: Ilyas Mustafajev, MD
  phone: +31683358037
  email: ilyas.mustafajev@radboudumc.nl
  last name: Rick Meijer, MD. PHD
  email: rick.meijer@radboudumc.nl
  facility: 
  contact: 
  country: Netherlands
  responsible party type: Sponsor-Investigator
  investigator affiliation: Radboud University Medical Center
  investigator full name: Cees Tack
  investigator title: Prof. Dr.
  mesh term: Diabetes Mellitus
  mesh term: Hypoglycemia
  mesh term: Diabetes Mellitus, Type 1
  mesh term: Epinephrine
  mesh term: Racepinephrine
  mesh term: Epinephryl borate
  sharing ipd: Yes
  ipd description: WE will share the study protocol using a data respository accesible through the research team on demand. Starting around 6 months after publication.
  ipd info type: Study Protocol
  ipd time frame: 6 months after publication
  ipd access criteria: The coordinating researcher will review acces requests. Seeing as the data are all anonimised acces will be granted for additional research in the field of inflammation or diabetes.