Oral Ketone Monoester Supplementation and Resting-state Brain Connectivity

NCT05992571 | Unknown

• 1 other identifier: rs-KME
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cerebrovascular Function; Cognition

Keywords

Beta-hydroxybutyrate (β-OHB); cerebral blood flow; cognition; brain connectivity

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Working memory

  90 minutes

• Executive function

  90 minutes

• Attention and working memory

  90 minutes

Other Outcomes (2)

• Mean arterial pressure

  90 minutes

• Plasma beta-hydroxybutyrate

  90 minutes

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Single dose of a taste-matched calorie-free placebo

Other: Placebo

β-OHB

EXPERIMENTAL

Single dose of a ketone monoester (\[R\]-3-hydroxybutyl \[R\]-3-hydroxybutyrate; 0.6 g β-OHB/kg body weight)

Dietary Supplement: β-OHB

Interventions

Placebo OTHER

Ingestion of a taste-matched calorie-free placebo drink followed by 90 minutes of rest.

Placebo

β-OHB DIETARY_SUPPLEMENT

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.

β-OHB

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead
• Alzheimer's Society of Brant, Haldimand Norfolk, Hamilton Halton: collaborator

Study Sites (1)

McMaster University

Hamilton, Ontario, L8S 4K1, Canada

RECRUITING

Study Officials

• Jeremy Walsh, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeremy Walsh, PhD

CONTACT

905-525-9140; walshj18@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: August 15, 2023
• Study Start: October 25, 2023
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: December 1, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Anyone who wishes to access the data.

Locations

CA (1)