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

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.

...

Conditions

• Metabolic Syndrome
• Normal Cognition

Interventions

DIETARY_SUPPLEMENT

Ketone Ester drink

The main ingredient of the Ketone Ester drink \[(R)-3-hydroxybutyl (R)-3-hydroxybutyrate)\] is regulated as GRAS (Generally Recognized as Safe) substance by the FDA (https://www.accessdata.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices\&id=515). The Ketone Ester compound is already being sold in the market as a ketogenic supplement and is especially popular among athletes, such as cyclists (sold by the official website of the company TdeltaS(R) Global (https://www.deltagketones.com/products/g-ketone-performance). The dose and formulation (25 g of KE contained in 59 ml of a drink), daily scheme (3 times daily) and total duration (28 days) are identical to a previous safety human study. The Ketone Ester drink provided by DeltaG will be repackaged by the NIA Pharmacist into new bottles identical to the ones that will be used for the placebo to ensure the blinding of participants and researchers to the drink.

DIETARY_SUPPLEMENT

Placebo: isocaloric dextrose drink

The main content of the Placebo will be an aqueous solution containing approximately 35 g of dextrose, a fruity flavor powder and stevia. We will also add Denatonium Benzoate (Bittrex) to match the bitterness of the Ketone Ester drink. The placebo will be prepared and dispensed by the NIA Pharmacist.

Sponsors & Collaborators

• National Institute on Aging (NIA)

  lead NIH

Principal Investigators

• Dimitrios I Kapogiannis, M.D. · National Institute on Aging (NIA)

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-06-24

Primary Completion

2025-06-02

Completion

2025-06-02

Countries

• United States

Study Locations