Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults 55 Years Old or Older

Metabolic Syndrome Clinical Trial

Official title: 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

Status Recruiting

Clinical Trial 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.

Clinical Trial 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.

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: None. Additional endpoints will be exploratory.

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: None. The other endpoints will be exploratory.

Study Population: Males or females, of age >= 55 years who meet the criteria for MetS and are cognitively intact.

Phase: N/A - study of a dietary supplement.

Description of Sites/Facilities Enrolling Participants:

The study will take place at a single site, at the NIA Clinical Unit at the Medstar Harbor Hospital, Baltimore

Description of Study Intervention:

Oral KE drink [containing 25 g KE/(R)-3-hydroxybutyl (R)-3- hydroxybutyrate] vs isocaloric Placebo drink (containing dextrose) x 3 times/day x 28 +/- 3 days

Study Duration: 25 months

Participant Duration:

Up to 59 days (Screening Visit is followed by an initiation visit within 28 days and then 28 3 days receiving the drink supplement). ;

Related Conditions & MeSH terms

• Metabolic Syndrome
• Normal Cognition

• NCT number: NCT04421014
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Sarah Park, R.N.
• Phone: (410) 350-7315
• Email: sarah.park@nih.gov
• Status: Recruiting
• Phase: N/A
• Start date: June 24, 2021
• Completion date: March 31, 2025