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/NCT06032156</url>
    </required_header>
    <id_info>
      <org_study_id>kCBF</org_study_id>
      <nct_id>NCT06032156</nct_id>
    </id_info>
    <brief_title>Ketone Dose and Cerebral Blood Flow Study</brief_title>
    <acronym>kCBF</acronym>
    <official_title>The Acute Effects of a High Versus Low Dose of a Ketone Monoester Supplement on Cerebral Blood Flow and Cognition</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>McMaster University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>McMaster University</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>
        Ketone bodies are produced by the liver during periods of food scarcity or severe&#xD;
        carbohydrate restriction. Blood ketones are an alternative fuel source used by the brain,&#xD;
        heart, and skeletal muscle during periods of fasting. Further, ketones bodies act as a&#xD;
        signalling molecule that have pleiotropic effects that upregulate cellular stress-resistance&#xD;
        pathways throughout the body.&#xD;
  &#xD;
        Oral supplements containing exogenous ketones have recently become available and represent a&#xD;
        novel tool for increasing plasma ketone bodies without the need for dietary restriction.&#xD;
        Early evidence suggests that oral ketone supplements may enhance cerebral blood flow and&#xD;
        improve cognition. However, the dose-dependent effects of a single ketone supplement on&#xD;
        cerebral blood flow and cognition in young adults is currently unknown.&#xD;
  &#xD;
        The purpose of this study is to characterize the effects of ingesting a high versus low dose&#xD;
        of an oral ketone monoester on cerebral blood flow, circulating blood markers, and cognition&#xD;
        in young adults.&#xD;
  &#xD;
        As an exploratory aim, this study will investigate how oxygen uptake kinetics during&#xD;
        submaximal exercise are impacted 2 hours after ingestion of a ketone supplement. Recent&#xD;
        findings indicate that ketone supplementation may impair exercise performance due to the&#xD;
        physiological stress (i.e., pH disturbances) imposed by an acute ketone dose. Delaying&#xD;
        exercise onset by 2 hours after ingestion of a ketone supplement may enhance oxygen kinetics&#xD;
        in a dose-dependent manner.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">August 2024</completion_date>
    <primary_completion_date type="Anticipated">May 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>A randomized double-blind placebo-controlled crossover design will be used to test 3 conditions. Participants will consume 60 mL of a supplement containing: 1) a low β-OHB dose (0.3g/kg) body weight of the ketone monoester; [R]-3-hydroxybutyl [R]-3-hydroxybutyrate); 2) a high β-OHB dose (0.6g/kg body weight); or 3) a taste-matched calorie-free inert placebo drink.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Resting cerebral blood flow (CBF)</measure>
      <time_frame>2-hour</time_frame>
      <description>Measured via duplex ultrasound of the extra-cranial arteries (internal carotid and vertebral arteries).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cognitive Function</measure>
      <time_frame>2-hour</time_frame>
      <description>The MST (Mnemonic Similarity Task) will be used to assess hippocampal-dependent memory and pattern separation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma beta-hydroxybutyrate area under the curve</measure>
      <time_frame>2-hour</time_frame>
      <description>Venous blood samples will be obtained via intravenous catheter</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Brain-derived neurotrophic factor (BDNF)</measure>
      <time_frame>2-hour, then following completion of submaximal exercise bout</time_frame>
      <description>Serum and plasma BDNF measured in venous blood samples will be obtained via intravenous catheter</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Oxygen uptake (VO2)</measure>
      <time_frame>2-hour, then during submaximal exercise (performed after 2-hour rest period)</time_frame>
      <description>Breath-by-breath analysis performed via metabolic cart</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>End-tidal CO2</measure>
      <time_frame>2-hour, then during submaximal exercise (performed after 2-hour rest period)</time_frame>
      <description>Breath-by-breath analysis performed via PowerLab Gas Analyzer (AD Instruments)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean arterial pressure (MAP)</measure>
      <time_frame>2-hour</time_frame>
      <description>Automated blood pressure cuff measurement of brachial artery pressure in mmHg.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Cerebrovascular Function</condition>
    <condition>Cognition</condition>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Single dose of a taste-matched calorie-free placebo</description>
    </arm_group>
    <arm_group>
      <arm_group_label>High Dose β-OHB</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.6 g β-OHB/kg body weight)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Low Dose β-OHB</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.3 g β-OHB/kg body weight)</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Low Dose β-OHB</intervention_name>
      <description>Ingestion of a low dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.3 g β-OHB/kg body weight) followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.</description>
      <arm_group_label>Low Dose β-OHB</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>High Dose β-OHB</intervention_name>
      <description>Ingestion of a high dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.6 g β-OHB/kg body weight) followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.</description>
      <arm_group_label>High Dose β-OHB</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Ingestion of a taste-matched calorie-free placebo drink followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          - Between the ages of 18 and 35&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Presence of obesity (body mass index &gt; 30 kg/m^2)&#xD;
  &#xD;
            -  Presence of known cardiovascular disease&#xD;
  &#xD;
            -  Presence of type 2 diabetes&#xD;
  &#xD;
            -  History of cardiovascular events requiring hospitalization (i.e., heart attack)&#xD;
  &#xD;
            -  History of concussion(s) with persistent symptoms&#xD;
  &#xD;
            -  Currently following a ketogenic diet and/or taking ketone body supplements&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>35 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jeremy J Walsh, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>McMaster University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jeremy J Walsh, PhD</last_name>
      <phone>905-525-9140</phone>
      <phone_ext>23523</phone_ext>
      <email>walshj18@mcmaster.ca</email>
    </overall_contact>
    <location>
      <facility>
        <name>McMaster University</name>
        <address>
          <city>Hamilton</city>
          <state>Ontario</state>
          <zip>L8S 4K1</zip>
          <country>Canada</country>
        </address>
      </facility>
      <contact>
        <last_name>Jeremy Walsh, PhD</last_name>
        <phone>9055259140</phone>
        <phone_ext>23523</phone_ext>
        <email>walshj18@mcmaster.ca</email>
      </contact>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>April 6, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Cerebral Blood Flow</keyword>
    <keyword>Cognition</keyword>
    <keyword>Beta-hydroxybutyrate (β-OHB)</keyword>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>The investigators will share individual patient data (de-identified) with researchers upon request</ipd_description>
    </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/NCT06032156
  org study id: kCBF
  nct id: NCT06032156
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Ketone bodies are produced by the liver during periods of food scarcity or severe
        carbohydrate restriction. Blood ketones are an alternative fuel source used by the brain,
        heart, and skeletal muscle during periods of fasting. Further, ketones bodies act as a
        signalling molecule that have pleiotropic effects that upregulate cellular stress-resistance
        pathways throughout the body.
  
        Oral supplements containing exogenous ketones have recently become available and represent a
        novel tool for increasing plasma ketone bodies without the need for dietary restriction.
        Early evidence suggests that oral ketone supplements may enhance cerebral blood flow and
        improve cognition. However, the dose-dependent effects of a single ketone supplement on
        cerebral blood flow and cognition in young adults is currently unknown.
  
        The purpose of this study is to characterize the effects of ingesting a high versus low dose
        of an oral ketone monoester on cerebral blood flow, circulating blood markers, and cognition
        in young adults.
  
        As an exploratory aim, this study will investigate how oxygen uptake kinetics during
        submaximal exercise are impacted 2 hours after ingestion of a ketone supplement. Recent
        findings indicate that ketone supplementation may impair exercise performance due to the
        physiological stress (i.e., pH disturbances) imposed by an acute ketone dose. Delaying
        exercise onset by 2 hours after ingestion of a ketone supplement may enhance oxygen kinetics
        in a dose-dependent manner.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: A randomized double-blind placebo-controlled crossover design will be used to test 3 conditions. Participants will consume 60 mL of a supplement containing: 1) a low β-OHB dose (0.3g/kg) body weight of the ketone monoester; [R]-3-hydroxybutyl [R]-3-hydroxybutyrate); 2) a high β-OHB dose (0.6g/kg body weight); or 3) a taste-matched calorie-free inert placebo drink.
  primary purpose: Basic Science
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Resting cerebral blood flow (CBF)
  time frame: 2-hour
  description: Measured via duplex ultrasound of the extra-cranial arteries (internal carotid and vertebral arteries).
  measure: Cognitive Function
  time frame: 2-hour
  description: The MST (Mnemonic Similarity Task) will be used to assess hippocampal-dependent memory and pattern separation.
  measure: Plasma beta-hydroxybutyrate area under the curve
  time frame: 2-hour
  description: Venous blood samples will be obtained via intravenous catheter
  measure: Brain-derived neurotrophic factor (BDNF)
  time frame: 2-hour, then following completion of submaximal exercise bout
  description: Serum and plasma BDNF measured in venous blood samples will be obtained via intravenous catheter
  measure: Oxygen uptake (VO2)
  time frame: 2-hour, then during submaximal exercise (performed after 2-hour rest period)
  description: Breath-by-breath analysis performed via metabolic cart
  measure: End-tidal CO2
  time frame: 2-hour, then during submaximal exercise (performed after 2-hour rest period)
  description: Breath-by-breath analysis performed via PowerLab Gas Analyzer (AD Instruments)
  measure: Mean arterial pressure (MAP)
  time frame: 2-hour
  description: Automated blood pressure cuff measurement of brachial artery pressure in mmHg.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Single dose of a taste-matched calorie-free placebo
  arm group label: High Dose β-OHB
  arm group type: Experimental
  description: Single dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.6 g β-OHB/kg body weight)
  arm group label: Low Dose β-OHB
  arm group type: Experimental
  description: Single dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.3 g β-OHB/kg body weight)
  intervention type: Dietary Supplement
  intervention name: Low Dose β-OHB
  description: Ingestion of a low dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.3 g β-OHB/kg body weight) followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.
  arm group label: Low Dose β-OHB
  intervention type: Dietary Supplement
  intervention name: High Dose β-OHB
  description: Ingestion of a high dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.6 g β-OHB/kg body weight) followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.
  arm group label: High Dose β-OHB
  intervention type: Other
  intervention name: Placebo
  description: Ingestion of a taste-matched calorie-free placebo drink followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 35 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Jeremy J Walsh, PhD
  role: Principal Investigator
  affiliation: McMaster University
  last name: Jeremy J Walsh, PhD
  phone: 905-525-9140
  phone ext: 23523
  email: walshj18@mcmaster.ca
  facility: 
  contact: 
  country: Canada
  responsible party type: Sponsor
  sharing ipd: Undecided
  ipd description: The investigators will share individual patient data (de-identified) with researchers upon request