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/NCT05992571</url>
    </required_header>
    <id_info>
      <org_study_id>rs-KME</org_study_id>
      <nct_id>NCT05992571</nct_id>
    </id_info>
    <brief_title>Oral Ketone Monoester Supplementation and Resting-state Brain Connectivity</brief_title>
    <official_title>The Impact of Acute Oral Ketone Monoester Supplementation on Resting-state Brain Connectivity in Adults With Memory Complaints</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>McMaster University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Alzheimer's Society of Brant, Haldimand Norfolk, Hamilton Halton</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </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>
        People who report subjective memory complaints have a greater risk of developing dementia.&#xD;
        Memory issues may be an early warning sign of dysfunctional cerebral glucose metabolism and&#xD;
        cerebral blood flow. Interventions that can restore cerebral metabolism and enhance cerebral&#xD;
        blood flow may protect against conversion to dementia. Exogenous ketone supplements have been&#xD;
        shown rapidly improves brain network function in young adults. Further, infusion studies&#xD;
        demonstrate that ketone bodies enhance cerebral blood flow in cognitively normal adults.&#xD;
        Whether acute ketone monoester supplementation can improve brain function in adults with&#xD;
        subjective memory complaints is currently unknown.&#xD;
  &#xD;
        This study will investigate the effects of a single ketone monoester dose on resting-state&#xD;
        functional connectivity in the default mode network and resting cerebral blood flow in adults&#xD;
        with subjective memory complaints.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">August 2024</completion_date>
    <primary_completion_date type="Anticipated">August 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 two conditions. Participants will consume 60 mL of: 1) a drink containing a ketone monoester supplement ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.3 g β-OHB/kg body weight); and 2) 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>Brain network connectivity</measure>
      <time_frame>90 minutes</time_frame>
      <description>Functional connectivity of the default mode network (DMN) is measured via functional MRI. Changes in BOLD signal in each region are determined by independent component analysis and then functional connectivity is measured as a Pearson correlation (r) between the neural regions comprising the DMN and transformed into a z score.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cerebral blood flow</measure>
      <time_frame>90 minutes</time_frame>
      <description>Sum of blood flow in the internal carotid and vertebral arteries via phase contrast MRI in ml/min.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Working memory</measure>
      <time_frame>90 minutes</time_frame>
      <description>Computer battery to assess working memory (n-back test) based on N2 reaction time</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Executive function</measure>
      <time_frame>90 minutes</time_frame>
      <description>Computer battery to assess executive function (Stroop test) based on Stroop Cost (reaction times to incongruent stimuli minus congruent stimuli).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Attention and working memory</measure>
      <time_frame>90 minutes</time_frame>
      <description>Computer battery to assess working memory (digit symbol substitution task) based on the number of correct responses in 120 seconds.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Mean arterial pressure</measure>
      <time_frame>90 minutes</time_frame>
      <description>Automated blood pressure cuff measurement of brachial artery pressure in mmHg.</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma beta-hydroxybutyrate</measure>
      <time_frame>90 minutes</time_frame>
      <description>Measured via finger capillary samples in mM</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</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>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>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Ingestion of a taste-matched calorie-free placebo drink followed by 90 minutes of rest.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>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 90 minutes of rest.</description>
      <arm_group_label>β-OHB</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  between the ages of 55 and 70&#xD;
  &#xD;
            -  presence of subjective memory complaints as determined by the Prospective-&#xD;
               Retrospective Memory Questionnaire&#xD;
  &#xD;
            -  cognitively normal, e.g. score ≥26 on the Montreal Cognitive Assessment&#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 (e.g., heart attack,&#xD;
               stroke)&#xD;
  &#xD;
            -  History of concussion(s) with persistent symptoms&#xD;
  &#xD;
            -  Currently following a ketogenic diet and/or taking ketone body supplements&#xD;
  &#xD;
            -  Diagnosis of any form of Alzheimer's disease or dementia&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>55 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jeremy Walsh, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>McMaster University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jeremy Walsh, PhD</last_name>
      <phone>905-525-9140</phone>
      <phone_ext>23523</phone_ext>
      <email>walshj18@mcmaster.ca</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>McMaster University</investigator_affiliation>
      <investigator_full_name>Jeremy Walsh</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>Beta-hydroxybutyrate (β-OHB)</keyword>
    <keyword>cerebral blood flow</keyword>
    <keyword>cognition</keyword>
    <keyword>brain connectivity</keyword>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>The investigators will share individual patient data (de-identified) with researchers upon request.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>Beginning 9 months and ending 36 months following article publication.</ipd_time_frame>
      <ipd_access_criteria>Anyone who wishes to access the data.</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/NCT05992571
  org study id: rs-KME
  nct id: NCT05992571
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  People who report subjective memory complaints have a greater risk of developing dementia.
        Memory issues may be an early warning sign of dysfunctional cerebral glucose metabolism and
        cerebral blood flow. Interventions that can restore cerebral metabolism and enhance cerebral
        blood flow may protect against conversion to dementia. Exogenous ketone supplements have been
        shown rapidly improves brain network function in young adults. Further, infusion studies
        demonstrate that ketone bodies enhance cerebral blood flow in cognitively normal adults.
        Whether acute ketone monoester supplementation can improve brain function in adults with
        subjective memory complaints is currently unknown.
  
        This study will investigate the effects of a single ketone monoester dose on resting-state
        functional connectivity in the default mode network and resting cerebral blood flow in adults
        with subjective memory complaints.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: A randomized double-blind placebo-controlled crossover design will be used to test two conditions. Participants will consume 60 mL of: 1) a drink containing a ketone monoester supplement ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.3 g β-OHB/kg body weight); and 2) a taste-matched calorie-free inert placebo drink.
  primary purpose: Basic Science
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Brain network connectivity
  time frame: 90 minutes
  description: Functional connectivity of the default mode network (DMN) is measured via functional MRI. Changes in BOLD signal in each region are determined by independent component analysis and then functional connectivity is measured as a Pearson correlation (r) between the neural regions comprising the DMN and transformed into a z score.
  measure: Cerebral blood flow
  time frame: 90 minutes
  description: Sum of blood flow in the internal carotid and vertebral arteries via phase contrast MRI in ml/min.
  measure: Working memory
  time frame: 90 minutes
  description: Computer battery to assess working memory (n-back test) based on N2 reaction time
  measure: Executive function
  time frame: 90 minutes
  description: Computer battery to assess executive function (Stroop test) based on Stroop Cost (reaction times to incongruent stimuli minus congruent stimuli).
  measure: Attention and working memory
  time frame: 90 minutes
  description: Computer battery to assess working memory (digit symbol substitution task) based on the number of correct responses in 120 seconds.
  measure: Mean arterial pressure
  time frame: 90 minutes
  description: Automated blood pressure cuff measurement of brachial artery pressure in mmHg.
  measure: Plasma beta-hydroxybutyrate
  time frame: 90 minutes
  description: Measured via finger capillary samples in mM
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Single dose of a taste-matched calorie-free placebo
  arm group label: 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)
  intervention type: Other
  intervention name: Placebo
  description: Ingestion of a taste-matched calorie-free placebo drink followed by 90 minutes of rest.
  arm group label: Placebo
  intervention type: Dietary Supplement
  intervention name: β-OHB
  description: Ingestion of a high dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.6 g β-OHB/kg body weight) followed by 90 minutes of rest.
  arm group label: β-OHB
  criteria: 
  gender: All
  minimum age: 55 Years
  maximum age: 70 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Jeremy Walsh, PhD
  role: Principal Investigator
  affiliation: McMaster University
  last name: Jeremy Walsh, PhD
  phone: 905-525-9140
  phone ext: 23523
  email: walshj18@mcmaster.ca
  responsible party type: Principal Investigator
  investigator affiliation: McMaster University
  investigator full name: Jeremy Walsh
  investigator title: Assistant Professor
  sharing ipd: Yes
  ipd description: The investigators will share individual patient data (de-identified) with researchers upon request.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Analytic Code
  ipd time frame: Beginning 9 months and ending 36 months following article publication.
  ipd access criteria: Anyone who wishes to access the data.