Clinical trial NCT06588946: Β-OHB Supplementation and Brain Health in Older Adults
Official title: The Effect of Exogenous Β-OHB Supplementation on Cerebral Blood Flow and Functional Brain Characteristics in Adults with Subjective Cognitive Decline
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Subjective Cognitive Decline
Keywords: early-stage dementia
ketone monoester supplementation
cerebral blood flow
cognition
resting state functional magnetic resonance imaging
placebo
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Heart and Stroke Foundation of Canada
First posted: 2024-09-19
Enrollment: 48
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: placebo-controlled
Primary purpose: BASIC_SCIENCE

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.

Detailed description: In this randomized placebo-controlled crossover double-blind designed clinical trial, 48 adults with SCD (50% female; aged 55 to 75 years old) will be allocated to a ketone monoester (KME) or placebo condition in random order (e.g., A-B or B-A), stratified by sex. Participants will be recruited from the local community through McMaster University, the local Alzheimer Society, and community outreach.

In total, participants will be asked to complete 5 visits. Data will be collected at a single site in Hamilton, Ontario associated with McMaster University. All interested individuals will complete an eligibility screening study visit (Visit 1) to establish inclusion/exclusion. Written, informed consent will be obtained before data collection. Demographic information and medical history will be collected at the beginning of Visit 1 to obtain information regarding medication use, medical history, age, years of education, and sex and gender-based variables. This information will be collected using a participant history questionnaire and the GENESIS-PRAXY questionnaire. Participants will also be introduced to the lab and the different tests that we will run during the experimental visits. Data will be collected at two time points for each condition: 1) Pre-intervention (Visits 2 \& 4: baseline); and post-intervention (Visits 3 \& 5: following 14-day intervention). In a randomized crossover design, participants will be randomly allocated to a condition (placebo or KME) for a 14-day intervention. Participants will then undergo a washout period, afterwhich participants will be complete the alternate condition including baseline data collection (Visit 4) and post-intervention visit (Visit 5) after the second 14-day intervention period.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Global cerebral blood flow (gCBF)
timeFrame: Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions
measure: Resting-state functional connectivity
timeFrame: Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions
Secondary outcomes:
measure: Cognitive testing
timeFrame: Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions
measure: Microstructural white matter health
timeFrame: Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions
measure: Cerebrovascular reactivity
timeFrame: Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions
measure: Blood-borne biomarkers
timeFrame: Baseline and post-intervention (i.e., 14-days later) for both KME and placebo conditions
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
Study officials:
affiliation: McMaster University
name: Jeremy Walsh, PhD
role: PRINCIPAL_INVESTIGATOR
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