Recruiting

Ketone MonoesterEffects of Exogenous Ketones on Cognitive Function in Older Adults With Prediabetes?

Sponsor:

University of Alabama at Birmingham

Code:

NCT07546409

Conditions

Prediabetes

Healthy (Controls)

Eligibility Criteria

Sex: All

Age: 60 - 70+

Healthy Volunteers: Accepted

Interventions

Ketone Monoester (KE)

Placebo

Study Details

Brief summary:

Brief Summary

The goal of this clinical trial is to learn whether older adults with prediabetes, but no diagnosed cognitive impairment, show early changes in brain energy use and thinking speed compared to older adults with normal blood sugar levels. The study will also test whether a single dose of an exogenous ketone supplement can improve brain energy use and cognitive processing speed.

The main questions it aims to answer are:

Do older adults with prediabetes have lower brain glucose uptake and slower cognitive processing speed compared to those with normal glucose levels?

Does a single dose of an exogenous ketone monoester supplement improve cognitive processing speed and brain glucose uptake?

Researchers will compare older adults with prediabetes to older adults with normal glucose levels to determine whether differences exist in brain glucose metabolism and cognitive performance. In a subset of participants, researchers will also compare brain and cognitive outcomes before and after consuming a ketone monoester supplement (DeltaG, Oxford, England).

Participants will:

Complete metabolic testing to determine glucose status

Undergo brain imaging using fluorodeoxyglucose positron emission tomography combined with magnetic resonance imaging (18FDG-PET/MRI) while performing a cognitive processing speed task

Consume a single dose of a commercially available ketone monoester supplement during one study visit

Complete cognitive testing during imaging to measure processing speed and brain activity

The results of this study will help determine whether early metabolic dysfunction is linked to reduced brain energy use and whether ketones can temporarily support brain function in individuals at risk for dementia.

Conditions

Prediabetes

Healthy (Controls)

Study ID

NCT07546409

Start date

May 20, 2025

Status verified date

Jun, 2026

Completion date

May 31, 2027

Anticipated

Primary completion date

May 31, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 60 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

Age 60 to 75 years
Able to provide written informed consent
Fluent in English
No diagnosed cognitive impairment or dementia

Classified as either:

Prediabetes (based on American Diabetes Association criteria), or Normal glucose regulation (control group)
Medically stable and cleared to undergo positron emission tomography and magnetic resonance imaging
Willing to comply with study procedures, including metabolic testing, supplement ingestion, and neuroimaging

Exclusion Criteria:

Diagnosis of mild cognitive impairment, dementia, or other neurodegenerative disorder
Diagnosis of type 1 diabetes or type 2 diabetes
Use of glucose-lowering medications (e.g., insulin, metformin, glucagon-like peptide-1 receptor agonists)
History of major neurological disorder (e.g., stroke, traumatic brain injury with loss of consciousness >30 minutes, epilepsy, multiple sclerosis)
Major psychiatric disorder not stable on treatment
Uncontrolled hypertension or significant cardiovascular disease
Severe renal, hepatic, or gastrointestinal disease that may affect supplement metabolism
Contraindications to magnetic resonance imaging (e.g., non-compatible implanted devices, severe claustrophobia)

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Ketone

placebo comparator: Placebo

Interventions

Ketone Monoester (KE)

The intervention is a single acute oral dose of a commercially available ketone monoester supplement (DeltaG®, Oxford, England). The active ingredient, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is rapidly metabolized after ingestion to raise circulating beta-hydroxybutyrate concentrations without requiring dietary carbohydrate restriction or fasting. The supplement is administered under supervised conditions during a study visit. Brain imaging with fluorodeoxyglucose F18 positron emission tomography combined with magnetic resonance imaging is performed during the post-ingestion period while participants complete a cognitive processing speed task. This protocol evaluates the immediate metabolic and neurocognitive effects of exogenous ketone administration within a single session.

Placebo

The placebo consists of a taste-, color-, and volume-matched beverage formulated to mimic the sensory characteristics of the ketone monoester supplement but containing no active ketone ingredient. The placebo does not contain (R)-3-hydroxybutyl (R)-3-hydroxybutyrate) and does not elevate circulating beta-hydroxybutyrate concentrations.

The placebo beverage will be administered orally under supervised research conditions during a study visit using procedures identical to the active supplement condition. Brain imaging with fluorodeoxyglucose F18 positron emission tomography combined with magnetic resonance imaging will be performed during the post-ingestion period while participants complete a cognitive processing speed task. This control condition allows isolation of the metabolic effects of ketone elevation from expectancy or beverage-related effects.

Primary outcome measure

Regional brain glucose uptake [ Time Frame: Two visits (placebo and ketone condition in random order) will take place within 4 weeks of enrollment. Main outcome is change in cerebral glucose uptake between placebo and ketone conditions. ]

Central Contacts and Locations

Central contacts

Katherine Sweatt, PhD

205-975-5398 sksweatt@uab.edu

Locations

UAB Comprehensive Cancer Center

Recruiting

Birmingham, Alabama, United States, 35205

Contacts

Sarah K Sweatt, PhD

205-975-5398 sksweatt@uab.edu

Webb Nutrition Sciences Building

Recruiting

Birmingham, Alabama, United States, 35205

Contacts

Sarah K Sweatt, PhD

205-975-5398 sksweatt@uab.edu

Principal Investigator:

Sarah K Sweatt, PhD

More Information

Sponsor

University of Alabama at Birmingham

Last update posted

Jul 2, 2026

Last verified

Jun, 2026

Keywords

Prediabetic State
Insulin Resistance
Brain Glucose Metabolism
Cerebral Glucose Uptake
Fluorodeoxyglucose F18
Positron-Emission Tomography
Magnetic Resonance Imaging
Functional Magnetic Resonance Imaging
Cognitive Dysfunction
Dementia
Aging
Processing Speed
Ketone Bodies
beta-Hydroxybutyrate
Neuroimaging
Brain Energy Metabolism

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Alabama at Birmingham on 2026-07-02.