Oral Ketone Monoester Supplementation and Resting-state Brain Connectivity

The Impact of Acute Oral Ketone Monoester Supplementation on Resting-state Brain Connectivity in Adults With Memory Complaints

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.

Study Overview

• Status: Recruiting
• Conditions: Cognition; Cerebrovascular Function
• Intervention / Treatment: Other: Placebo; Dietary supplement: β-OHB

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jeremy Walsh, PhD; Phone Number: 23523 905-525-9140; Email: walshj18@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • Recruiting
      • McMaster University
      • Contact: Jeremy Walsh, PhD; Phone Number: 23523 9055259140; Email: walshj18@mcmaster.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• between the ages of 55 and 70
• presence of subjective memory complaints as determined by the Prospective- Retrospective Memory Questionnaire
• cognitively normal, e.g. score ≥26 on the Montreal Cognitive Assessment

Exclusion Criteria:

• Presence of obesity (body mass index > 30 kg/m^2)
• Presence of known cardiovascular disease
• Presence of type 2 diabetes
• History of cardiovascular events requiring hospitalization in the past 3 years (e.g., heart attack, stroke)
• History of concussion(s) with persistent symptoms
• Currently following a ketogenic diet and/or taking ketone body supplements
• Diagnosis of any form of Alzheimer's disease or dementia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Single dose of a taste-matched calorie-free placebo	Other: Placebo; Ingestion of a taste-matched calorie-free placebo drink followed by 90 minutes of rest.
Experimental: β-OHB; Single dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.6 g β-OHB/kg body weight)	Dietary supplement: β-OHB; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain network connectivity	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.	90 minutes
Cerebral blood flow	Sum of blood flow in the internal carotid and vertebral arteries via phase contrast MRI in ml/min.	90 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Working memory	Computer battery to assess working memory (n-back test) based on N2 reaction time	90 minutes
Executive function	Computer battery to assess executive function (Stroop test) based on Stroop Cost (reaction times to incongruent stimuli minus congruent stimuli).	90 minutes
Attention and working memory	Computer battery to assess working memory (digit symbol substitution task) based on the number of correct responses in 120 seconds.	90 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean arterial pressure	Automated blood pressure cuff measurement of brachial artery pressure in mmHg.	90 minutes
Plasma beta-hydroxybutyrate	Measured via finger capillary samples in mM	90 minutes

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Alzheimer's Society of Brant, Haldimand Norfolk, Hamilton Halton
• Investigators: Principal Investigator: Jeremy Walsh, PhD, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: June 7, 2023
• First Submitted That Met QC Criteria: August 7, 2023
• First Posted (Actual): August 15, 2023

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: cognition; cerebral blood flow; brain connectivity; Beta-hydroxybutyrate (β-OHB)
• Other Study ID Numbers: rs-KME

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators will share individual patient data (de-identified) with researchers upon request.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Anyone who wishes to access the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No