Β-OHB Supplementation and Brain Health in Older Adults
ConditionSubjective Cognitive Decline
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age55-75
SponsorMcMaster University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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)
Trial design
Design model
Crossover
Treatments tested in this trial
Ketone monoester (KME) supplement
Dietary supplement15g 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).
Placebo supplement
Dietary supplement50mL 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.
Treatment groups
48 Participants
are divided into 2 treatment groupsGroup A: Ketone monoester (KME) supplementExperimental treatment 1 intervention
Group B: Placebo supplementPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions2
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.
Time frame
Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditionsSecondary outcomes
1
Cognitive testing
A battery of computerized validated psychometric tests will be used, including: the Mnemonic similarities task (MST) to assess hippocampal-dependent learning and memory, the Stroop colour-word task to assess processing speed, working memory, attention, and inhibitory control, and a shortened version of the Odd-One-Out test to measure working memory and executive function. A non-computerized dual-task test will be performed to assess the multitasking ability of walking while performing another cognitive task.
Time frame
Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions2
Microstructural white matter health
Dual spin echo, echo-planar imaging (EPI) diffusion tensor imaging (DTI) sequence collected by magnetic resonance imaging (MRI) to assess brain white matter microstructural integrity.
Time frame
Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions3
Cerebrovascular reactivity
The phase contrast flow sensitizing MRI pulse and resting state functional MRI sequences will both be repeated while participants undergo an elevated CO2 breathing task. Cerebrovascular function will be calculated from the stimulus-response relationship between PaCO2 and (1) phase contrast: cross sectional areas of the internal carotid and vertebral arteries, and (2) rsfMRI: % change BOLD/mmHg.
Time frame
Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions4
Blood-borne biomarkers
A venous blood sample will be collected to assess circulating concentrations of various hormones and metabolites (e.g., brain-derived neurotrophic factor \[BDNF\]) that relate to brain health, metabolism, and inflammation.
Time frame
Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditionsSponsors and contacts
Click on the lead sponsor to view all of their trials.
McMaster University
Lead sponsor
Heart and Stroke Foundation of Canada
Collaborator
Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: