Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults >= 55 Years Old. A Double-Blinded Randomized Controlled Clinical Trial.
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Metabolic Syndrome
- Sponsor
- National Institute on Aging (NIA)
- Enrollment
- 99
- Locations
- 1
- Primary Endpoint
- Brain concentration of BHB using brain Magnetic Resonance Spectroscopy
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
Background:
In Alzheimer s disease (AD) the brain cannot use glucose as a fuel. The brain can use ketones as a fuel instead of glucose. Researchers want to test a supplement, Ketone Ester (KE). It may improve brain metabolic function and cognition in normal people and, perhaps, down the road, in patients with AD.
Objective:
To study the change in brain ketone levels in people after 28 days of taking KE compared with baseline and placebo. Also, to study changes in cognitive performance.
Eligibility:
People 55 years old or older with metabolic syndrome and no cognitive impairment
Design:
Participants will have 4 visits.
Participants will be screened at Visit 1 with:
Medical history
Physical exam
Blood and urine tests
Cognitive testing
Participants will be randomly assigned to receive either the study supplement or a placebo with same amount of calories. Neither they nor the researchers will know which they receive.
Visit 2 will include repeats of some screening tests. It will also include:
Stool sample (brought from home)
MRI/MRS: Participants will lie on a table that slides in and out of a scanner. A coil will be placed over their head. They may be asked to perform leg exercises.
First dose of study supplement or placebo
About 2 weeks after Visit 2, Visit 3 will include blood and urine tests and a questionnaire.
About 2 weeks after Visit 3, Visit 4 will include repeats of the Visit 2 tests.
Participants will drink the study supplement or placebo 3 times per day during the study. They will keep a daily log of each dose. They will bring the log to Visits 3 and 4.
Participants will by contacted by phone once per week during the study to see how they are doing.
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Detailed Description
Study Description: We hypothesize that supplementation with a ketone ester drink \[Ketone Ester (KE)\] compared to placebo, in cognitively intact adults \>= 55 years old with Metabolic Syndrome (MetS), will (i) increase peripheral and brain ketone levels \[primarily beta-hydroxybutyrate (BHB) and secondarily acetoacetate (AcAc)\], (ii) improve neuronal/astrocytic insulin resistance (IR) and induce a change in neuronal/astrocytic metabolism as reflected on blood Extracellular Vesicle (EV) biomarkers, (iii) improve cognitive performance, (iv) boost mitochondrial function in muscle, and (v) change gut microbiome. These effects will be examined acutely, after single-dose administration, and chronically, after 28 days on the supplement x 3 times per day. The changes in EV biomarkers and cognition will be associated with the elevation of ketones in brain. The study will involve a Screening Visit and three additional Visits to assess acute effects, compliance and chronic effects, respectively, and a follow-up visit to obtain DNA. Objectives: Primary: To investigate the change in brain concentration BHB, using brain Magnetic Resonance Spectroscopy, after 28 days of supplementation with the KE, compared to baseline and placebo. Secondary: To test the hypothesis that genetic factors may affect the response to the KE supplement. Endpoints: Primary: To detect with brain MRS, a significant change in the concentration of BHB, after 28 days of supplementation with the KE compared to baseline and placebo Secondary: To assess whether genetic factors modulate the response to the KE supplement.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Brain concentration of BHB using brain Magnetic Resonance Spectroscopy
Time Frame: 28 days - outcome assessed at Visit 2 (baseline measurement before the first dose and after 75 min); Visit 4 (before and after 75 min from last dose).
To detect with brain MRS, a significant change in the concentration of BHB, after 28 days of supplementation with the Ketone Ester drink compared to baseline and placebo.