Β-OHB Supplementation and Brain Health in Older Adults

NCT06588946 | Not Yet Recruiting Phase 2

• 1 other identifier: 05992572
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this randomized placebo controlled crossover trial is investigate the effects of short-term ketone monoester (KME) supplementation to brain function in older adults with subjective cognitive decline. We will test the hypothesis that KME supplementation will increase cerebral blood flow and improve resting-state functional connectivity in the brain compared to placebo supplementation in older adults with subjective cognitive decline. Participants will be randomly assigned to either placebo of KME supplementation for 14 days. Following a washout period, participants will complete the alternate condition for 14 days. Outcome measures will be assessed before and after each intervention period.

Conditions

Subjective Cognitive Decline

Keywords

early-stage dementia; ketone monoester supplementation; cerebral blood flow; cognition; resting state functional magnetic resonance imaging; placebo

Outcome Measures

Primary Outcomes (2)

• Global cerebral blood flow (gCBF)

  Measured by magnetic resonance imaging (MRI) under resting, normocapnic conditions. Arterial flow measurement will be performed using a phase contrast flow sensitizing MRI pulse sequence. Cross-sectional areas and mean blood flow of the carotid and vertebral arteries will be measured, with total blood flow in all four vessels equaling global CBF.

  Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions

• Resting-state functional connectivity

  A resting state functional magnetic resonance imaging (rsfMRI) scan will be performed eyes closed using a gradient echo EPI sequence. The temporal and regional co-activation of brain regions in the resting state provide a measure of functional connectivity in the brain. rsfMRI data will be analyzed to measure global whole-brain functional connectivity and within localized brain regions of interest.

  Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions

Secondary Outcomes (4)

• Cognitive testing

  Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions

• Microstructural white matter health

  Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions

• Cerebrovascular reactivity

  Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions

• Blood-borne biomarkers

  Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions

Study Arms (2)

Ketone monoester (KME) supplement

EXPERIMENTAL

Participants will be instructed to consume a ketone monoester (KME) supplement prior to each meal (3x/day) for 14 days.

Dietary Supplement: Ketone monoester (KME) supplement

Placebo supplement

PLACEBO COMPARATOR

Participants will be instructed to consume a bottle of placebo supplement prior to each meal (3x/day) for 14 days.

Dietary Supplement: Placebo supplement

Interventions

Ketone monoester (KME) supplement DIETARY_SUPPLEMENT

15g of a KME supplement orally consumed 3x daily for 14 days. This dosing protocol raises plasma β-OHB consistently during the waking hours. Oral KME will be provided in opaque bottles labelled A or B to maintain condition blinding. Each bottle will contain a drink providing 15g of a KME supplement: \[R\]-3-hydroxybutyl \[R\]-3-hydroxybutyrate (ΔG®, TDeltaS, Oxford, UK).

Also known as: [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (ΔG®, TDeltaS, Oxford, UK)

Ketone monoester (KME) supplement

Placebo supplement DIETARY_SUPPLEMENT

50mL taste-match inert calorie-free placebo drink orally consumed 3x daily for 14 days. Oral placebo will be provided in opaque bottles labelled A or B to maintain condition blinding.

Placebo supplement

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Being objectively cognitively normal as determined by a Montreal Cognitive Assessment (MoCA) score ≥26 with independent living and ambulating
• SCD will be determined using the Prospective-Retrospective Memory Questionnaire (PRMQ) following the SCD Initiative Working Group framework

You may not qualify if:

• A diagnosis of mild cognitive impairment, dementia, or psychiatric and/or mood disorders (e.g., major depression)
• MoCA score \<26
• Diagnosis of cardiometabolic disease (e.g., hypertension, type 2 diabetes)
• Obesity (BMI \>30 kg/m2)
• History of heart attack or stroke
• History of smoking
• Currently following a ketogenic diet or taking ketogenic supplements
• Having MRI contraindications
• Participants with literacy, visual, hearing, and/or speech issues, as well as individuals who are not proficient in English will not be eligible for this trial

Sponsors & Collaborators

• McMaster University: lead
• Heart and Stroke Foundation of Canada: collaborator

Study Sites (1)

McMaster University

Hamilton, Ontario, L8S 4K1, Canada

Location

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MeSH Terms

Conditions

Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Jeremy Walsh, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Walsh

CONTACT

(905) 525-9140; walshj18@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: placebo-controlled

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: September 19, 2024
• Study Start: March 1, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 26, 2025

Record last verified: 2025-02

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: Researchers from a reputable institution who wish to access the data may submit a request to the Principal Investigator.

Locations

CA (1)