<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/NCT04466735</url>
  </required_header>
  <id_info>
    <org_study_id>2020-3448</org_study_id>
    <nct_id>NCT04466735</nct_id>
  </id_info>
  <brief_title>BRain Energy Activation With Ketones to Prevent Alzheimer's Disease</brief_title>
  <acronym>BREAK-AD</acronym>
  <official_title>6 Month Randomized Controlled Trial With D-beta-hydroxybutyrate in Mild Cognitive Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Université de Sherbrooke</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Alzheimer's Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nestle Health Science</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Université de Sherbrooke</source>
  <oversight_info>
    <has_dmc>Yes</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>
      A six month randomized controlled intervention with an exogenous ketone salt (EKS) supplement&#xD;
      in mild cognitive impairment. Participants will receive 15 g of the supplement twice daily&#xD;
      (equivalent to 24 g/day of EKS). Outcomes: brain energy metabolism, cognition, plasma&#xD;
      biomarkers, brain imaging (volumetric, functional, structural) and quality of life will be&#xD;
      analyzed before and after the intervention.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 15, 2020</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">February 2024</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Randomized controlled trial. First phase :Two parallel groups, one placebo, one active Second phase : All participants will be invited to take part in an open phase on the active product only.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Investigators, participants and outcome assessors will be fully blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Acetoacetate brain uptake</measure>
    <time_frame>6 months</time_frame>
    <description>CMRacac measured by PET Scan</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Glucose brain uptake</measure>
    <time_frame>6 months</time_frame>
    <description>CMRgluc measured by PET Scan</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cognition</measure>
    <time_frame>0-3-6-9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma biomarkers</measure>
    <time_frame>9 months</time_frame>
    <description>glucose, fatty acids, ketones</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Structural and functional brain measures</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">56</enrollment>
  <condition>MCI</condition>
  <arm_group>
    <arm_group_label>Active group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be on the active intervention for 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be on the placebo intervention for 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open phase on active product</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>At the end of the 6-month randomized controlled phase, participants will be unblinded and invited to continue on the active product for an additional 3 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Active group</intervention_name>
    <description>2 x 12 g of EKS/day</description>
    <arm_group_label>Active group</arm_group_label>
    <arm_group_label>Open phase on active product</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo group</intervention_name>
    <description>Isocaloric placebo supplement with similar salt load but no EKS</description>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The participant must answer Yes to the question ''Do you think your memory is not as&#xD;
             good as it was?''&#xD;
&#xD;
          -  Have a MoCA Score between 20/30 and 26/30&#xD;
&#xD;
          -  Have a QAF score of less than 9/30&#xD;
&#xD;
          -  Understand, read and talk French&#xD;
&#xD;
          -  Having good visual and hearing acuity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Major cognitive decline or neurodegenerative disease.&#xD;
&#xD;
          -  Already consuming a daily medium chain triglyceride or ketone supplement.&#xD;
&#xD;
          -  Soy, milk, gluten or allergy to the study product&#xD;
&#xD;
          -  Controlled or uncontrolled diabetes&#xD;
&#xD;
          -  Uncontrolled chronic disease&#xD;
&#xD;
          -  Vitamin B12 deficit&#xD;
&#xD;
          -  Clinical anomaly in the blood chemistry profile&#xD;
&#xD;
          -  QSP-9 score over 19/27&#xD;
&#xD;
          -  Taking an anti-cholinergic drugs&#xD;
&#xD;
          -  Recent change in medication&#xD;
&#xD;
          -  Active cancer in the last 2 years&#xD;
&#xD;
          -  General anesthesia in the last 6 months&#xD;
&#xD;
          -  history of alcohol abuse or dependence in the last 2 years&#xD;
&#xD;
          -  Participation in other interventional or PET research project&#xD;
&#xD;
          -  Unable to undergo an MRI or PET scan&#xD;
&#xD;
          -  History of kidney stones or hypercalcemia&#xD;
&#xD;
          -  History of cardiovascular events or insufficiency&#xD;
&#xD;
          -  Renal failure and / or creatinine &lt;58 umol or&gt; 110 umol for men and &lt;46 umol or&gt; 92&#xD;
             umol for women or if the GFR (glomerular filtration rate) &lt;60 ml / min / 1.73 m2&#xD;
&#xD;
          -  Chronic disease of the digestive system or intestinal malabsorption (celiac disease,&#xD;
             chronic pancreatitis, Crohn's disease, etc.)&#xD;
&#xD;
          -  Body mass index &lt;20 or voluntary weight loss of more than 5% in the last 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Rearsh Centre on Aging</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H4C4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mélanie Fortier, MSc</last_name>
      <phone>819-780-2220</phone>
      <phone_ext>45252</phone_ext>
      <email>melanie.fortier2@Usherbrooke.ca</email>
    </contact>
    <investigator>
      <last_name>Stephen Cunanne, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>April 17, 2023</last_update_submitted>
  <last_update_submitted_qc>April 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04466735
org study id: 2020-3448
nct id: NCT04466735
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A six month randomized controlled intervention with an exogenous ketone salt (EKS) supplement
      in mild cognitive impairment. Participants will receive 15 g of the supplement twice daily
      (equivalent to 24 g/day of EKS). Outcomes: brain energy metabolism, cognition, plasma
      biomarkers, brain imaging (volumetric, functional, structural) and quality of life will be
      analyzed before and after the intervention.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized controlled trial. First phase :Two parallel groups, one placebo, one active Second phase : All participants will be invited to take part in an open phase on the active product only.
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Investigators, participants and outcome assessors will be fully blinded.
measure: Acetoacetate brain uptake
time frame: 6 months
description: CMRacac measured by PET Scan
measure: Glucose brain uptake
time frame: 6 months
description: CMRgluc measured by PET Scan
measure: Cognition
time frame: 0-3-6-9 months
measure: Plasma biomarkers
time frame: 9 months
description: glucose, fatty acids, ketones
measure: Structural and functional brain measures
time frame: 6 months
arm group label: Active group
arm group type: Experimental
description: Participants will be on the active intervention for 6 months
arm group label: Placebo Group
arm group type: Placebo Comparator
description: Participants will be on the placebo intervention for 6 months
arm group label: Open phase on active product
arm group type: Active Comparator
description: At the end of the 6-month randomized controlled phase, participants will be unblinded and invited to continue on the active product for an additional 3 months.
intervention type: Dietary Supplement
intervention name: Active group
description: 2 x 12 g of EKS/day
arm group label: Active group
arm group label: Open phase on active product
intervention type: Dietary Supplement
intervention name: Placebo group
description: Isocaloric placebo supplement with similar salt load but no EKS
arm group label: Placebo Group
criteria: 
gender: All
minimum age: 55 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
status: Recruiting
contact: 
investigator: 
country: Canada
responsible party type: Sponsor