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/NCT05980858</url>
    </required_header>
    <id_info>
      <org_study_id>TZL-2-2023</org_study_id>
      <nct_id>NCT05980858</nct_id>
    </id_info>
    <brief_title>Effects of Exogenous Ketosis on Renal Function, Renal Perfusion, and Sodium Excretory Capacity in Healthy Subjects</brief_title>
    <acronym>KETO</acronym>
    <official_title>Effects of Exogenous Ketosis on Renal Function, Renal Perfusion, and Sodium Excretory Capacity in Healthy Subjects</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Gødstrup Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Gødstrup Hospital</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 is a randomized, placebo-controlled, double-blinded crossover design. Fifteen healthy&#xD;
        subjects will be randomized to receive either ketone bodies (KE4) or placebo delivered by&#xD;
        KetoneAid. After a period of 5-days treatment, effect variables will be measured (experiment&#xD;
        day 1). After a washout period of 14 days, the subjects are crossed over to a similar&#xD;
        treatment period with the other treatment. The study is terminated by measuring effect&#xD;
        variables after the second treatment period (experiment day 2).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background: Renewed interest in ketone bodies has emerged, partly driven by the recent&#xD;
        success of selective sodium glucose co transporter 2 (SGLT-2) inhibition in preventing&#xD;
        cardiovascular deaths in patients with diabetes mellitus (DM) and chronic kidney disease&#xD;
        (CKD). Effects of ketosis are of importance in order to understand the beneficial effects of&#xD;
        SGLT-2 inhibitors and to account for the full therapeutic potential of this treatment.&#xD;
  &#xD;
        Hypothesis: Ketosis increases renal blood flow and glomerular filtration rate (GFR).&#xD;
  &#xD;
        Methods: It is a randomized, placebo-controlled double-blinded cross over study. Fifteen&#xD;
        healthy subjects will be randomized to receive either ketone bodies (KE4) or for 5 days.&#xD;
        After a wash out period of at least 14 days, the subjects are crossed over to receive the&#xD;
        other treatment. After each treatment period effect variables will be measured including&#xD;
        Technetium(Tc)99m - Diethylenetriamine pentaacetate (DTPA) clearance and water based positron&#xD;
        emission tomography computed tomography (PET/CT)&#xD;
  &#xD;
        Perspectives: The study has the potential to provide information regarding the therapeutic&#xD;
        potential of treatment with ketone bodies and understanding of conditions characterized by&#xD;
        ketosis, such as SGLT2-inhibitor treatment.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">December 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>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>GFR</measure>
      <time_frame>Measured after each treatment period (day 6 and approximately day 26)</time_frame>
      <description>Change in GFR measured by Tc99m-DTPA clearance</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Renal Blood Flow (RBF)</measure>
      <time_frame>Subjects are scanned after each treatment period (day 6 and approximately day 26)</time_frame>
      <description>Change in RBF determined by water based PET/CT scans</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>24-hour blood pressure</measure>
      <time_frame>Measured after each treatment period (day 6 and approximately day 26)</time_frame>
      <description>Change in systolic 24-hour blood pressure</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Vasoactive hormones</measure>
      <time_frame>Measured after each treatment period (day 6 and approximately day 26)</time_frame>
      <description>Change in plasma levels of angiotensin II, aldosterone, renin, brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), copeptin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Beta-hydroxybutyrate</measure>
      <time_frame>Measured after each treatment period (day 6 and approximately day 26)</time_frame>
      <description>Change ind p-beta-hydroxybutyrate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Renal tubular transport proteins</measure>
      <time_frame>Measured after each treatment period (day 6 and approximately day 26)</time_frame>
      <description>Urine excretions of aquaporin 2 (AQP2), thiazide-sensitive sodium-chloride cotransporter (NCC) and distal epithelial sodium channel (ENaC)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">15</enrollment>
    <condition>Ketosis</condition>
    <condition>Ketonemia</condition>
    <arm_group>
      <arm_group_label>KetoneAid KE4, then Placebo drink</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>For five days each subject will receive beta-hydroxybutyrate (KE4), then crossed over to receive placebo drink for 5 days.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo drink, then KetoneAid KE4</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>For five days each subject will receive a placebo drink three times daily, then subjects are crossed over to receive beta-hydroxybutyrate (KE4).</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Beta-hydroxybutyrate</intervention_name>
      <description>Each subject receive Beta-hydroxybutyrate 300mg/kg x 3 for five days. After the treatment period effect variables will be examined.</description>
      <arm_group_label>KetoneAid KE4, then Placebo drink</arm_group_label>
      <arm_group_label>Placebo drink, then KetoneAid KE4</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Each subject receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.</description>
      <arm_group_label>KetoneAid KE4, then Placebo drink</arm_group_label>
      <arm_group_label>Placebo drink, then KetoneAid KE4</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  BMI &lt; 30 kg/m2&#xD;
  &#xD;
            -  Safe contraception if women in childbearing age&#xD;
  &#xD;
            -  Normal biochemical screening&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnancy or breast feeding&#xD;
  &#xD;
            -  Major heart-, liver-, kidney-, lung-, neurological- or endocrine disease&#xD;
  &#xD;
            -  Daily use of prescription drugs (expect for contraceptives)&#xD;
  &#xD;
            -  Alcohol or drug abuse&#xD;
  &#xD;
            -  Periodic fasting&#xD;
  &#xD;
            -  Routinely intake of ketogenic diet&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>30 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jesper N Bech, PhD, Prof</last_name>
      <role>Principal Investigator</role>
      <affiliation>University Clinic in Nephrology and Hypertension</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Trine Z Lyksholm, MD</last_name>
      <phone>28439136</phone>
      <phone_ext>0045</phone_ext>
      <email>trizur@rm.dk</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 5, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Gødstrup Hospital</investigator_affiliation>
      <investigator_full_name>Trine Lyksholm</investigator_full_name>
      <investigator_title>Principal investigator</investigator_title>
    </responsible_party>
    <keyword>Kidney circulation</keyword>
    <keyword>Kidney physiology</keyword>
    <keyword>Kidney function</keyword>
    <keyword>Glomerular Filtration Rate</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ketosis</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/NCT05980858
  org study id: TZL-2-2023
  nct id: NCT05980858
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a randomized, placebo-controlled, double-blinded crossover design. Fifteen healthy
        subjects will be randomized to receive either ketone bodies (KE4) or placebo delivered by
        KetoneAid. After a period of 5-days treatment, effect variables will be measured (experiment
        day 1). After a washout period of 14 days, the subjects are crossed over to a similar
        treatment period with the other treatment. The study is terminated by measuring effect
        variables after the second treatment period (experiment day 2).
  Background: Renewed interest in ketone bodies has emerged, partly driven by the recent
        success of selective sodium glucose co transporter 2 (SGLT-2) inhibition in preventing
        cardiovascular deaths in patients with diabetes mellitus (DM) and chronic kidney disease
        (CKD). Effects of ketosis are of importance in order to understand the beneficial effects of
        SGLT-2 inhibitors and to account for the full therapeutic potential of this treatment.
  
        Hypothesis: Ketosis increases renal blood flow and glomerular filtration rate (GFR).
  
        Methods: It is a randomized, placebo-controlled double-blinded cross over study. Fifteen
        healthy subjects will be randomized to receive either ketone bodies (KE4) or for 5 days.
        After a wash out period of at least 14 days, the subjects are crossed over to receive the
        other treatment. After each treatment period effect variables will be measured including
        Technetium(Tc)99m - Diethylenetriamine pentaacetate (DTPA) clearance and water based positron
        emission tomography computed tomography (PET/CT)
  
        Perspectives: The study has the potential to provide information regarding the therapeutic
        potential of treatment with ketone bodies and understanding of conditions characterized by
        ketosis, such as SGLT2-inhibitor treatment.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Basic Science
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: GFR
  time frame: Measured after each treatment period (day 6 and approximately day 26)
  description: Change in GFR measured by Tc99m-DTPA clearance
  measure: Renal Blood Flow (RBF)
  time frame: Subjects are scanned after each treatment period (day 6 and approximately day 26)
  description: Change in RBF determined by water based PET/CT scans
  measure: 24-hour blood pressure
  time frame: Measured after each treatment period (day 6 and approximately day 26)
  description: Change in systolic 24-hour blood pressure
  measure: Vasoactive hormones
  time frame: Measured after each treatment period (day 6 and approximately day 26)
  description: Change in plasma levels of angiotensin II, aldosterone, renin, brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), copeptin
  measure: Beta-hydroxybutyrate
  time frame: Measured after each treatment period (day 6 and approximately day 26)
  description: Change ind p-beta-hydroxybutyrate
  measure: Renal tubular transport proteins
  time frame: Measured after each treatment period (day 6 and approximately day 26)
  description: Urine excretions of aquaporin 2 (AQP2), thiazide-sensitive sodium-chloride cotransporter (NCC) and distal epithelial sodium channel (ENaC)
  arm group label: KetoneAid KE4, then Placebo drink
  arm group type: Active Comparator
  description: For five days each subject will receive beta-hydroxybutyrate (KE4), then crossed over to receive placebo drink for 5 days.
  arm group label: Placebo drink, then KetoneAid KE4
  arm group type: Active Comparator
  description: For five days each subject will receive a placebo drink three times daily, then subjects are crossed over to receive beta-hydroxybutyrate (KE4).
  intervention type: Dietary Supplement
  intervention name: Beta-hydroxybutyrate
  description: Each subject receive Beta-hydroxybutyrate 300mg/kg x 3 for five days. After the treatment period effect variables will be examined.
  arm group label: KetoneAid KE4, then Placebo drink
  arm group label: Placebo drink, then KetoneAid KE4
  intervention type: Other
  intervention name: Placebo
  description: Each subject receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.
  arm group label: KetoneAid KE4, then Placebo drink
  arm group label: Placebo drink, then KetoneAid KE4
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 30 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Jesper N Bech, PhD, Prof
  role: Principal Investigator
  affiliation: University Clinic in Nephrology and Hypertension
  last name: Trine Z Lyksholm, MD
  phone: 28439136
  phone ext: 0045
  email: trizur@rm.dk
  responsible party type: Principal Investigator
  investigator affiliation: Gødstrup Hospital
  investigator full name: Trine Lyksholm
  investigator title: Principal investigator
  mesh term: Ketosis
  sharing ipd: No