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

NCT07546409 | Active Not Recruiting

• 2 other identifiers: IRB-300013058UAB NORC
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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)

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

Outcome Measures

Primary Outcomes (1)

• Regional brain glucose uptake

  Regional brain glucose uptake measured by fluorodeoxyglucose F18 positron emission tomography. The primary outcome is regional cerebral glucose uptake quantified using fluorodeoxyglucose F18 positron emission tomography integrated with magnetic resonance imaging. Glucose uptake will be assessed in prespecified frontal and temporoparietal regions implicated in early metabolic and cognitive decline. Uptake values will be expressed as standardized uptake value ratios to allow regional comparison across participants. This outcome is used to determine (1) whether older adults with prediabetes exhibit reduced task-related brain glucose uptake compared to metabolically normal older adults, and (2) whether acute ketone monoester ingestion alters regional glucose uptake during cognitive task performance.

  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.

Study Arms (2)

Ketone

EXPERIMENTAL

Dietary Supplement: Ketone Monoester (KE)

Placebo

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

Ketone Monoester (KE) DIETARY_SUPPLEMENT

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.

Ketone

Placebo DIETARY_SUPPLEMENT

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.

Placebo

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (2)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35205, United States

Location

Webb Nutrition Sciences Building

Birmingham, Alabama, 35205, United States

Location

MeSH Terms

Conditions

Prediabetic State; Insulin Resistance; Cognitive Dysfunction; Dementia

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientist I

Study Record Dates

• First Submitted: April 10, 2026
• First Posted: April 22, 2026
• Study Start: May 20, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)