Ketone Esters for Appetite, Cognition, and Cardiovascular Function in Individuals With Obesity and Insulin Resistance

NCT05651243 | Completed

• 1 other identifier: 22-877
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this single-blind randomized placebo-controlled trial is to test the effects of an oral ketone supplement on appetite, cognition, metabolism, and cardiovascular function in individuals with obesity and insulin resistance. The main question\[s\] it aims to answer are:

• Does taking the ketone supplement reduce appetite and improve cognition?
• How does the ketone supplement alter metabolism and cardiovascular function? Participants will be asked to consume a randomly assigned ketone ester supplement or a placebo and testing will be done to see how the supplement affects the following compared to a placebo:
• appetite,
• cognition,
• metabolism
• cardiovascular function Researchers will compare individuals with obesity and insulin resistance to individuals with normal weight and no insulin resistance to see if the ketone supplement affects groups differently.

Conditions

Metabolic Syndrome

Outcome Measures

Primary Outcomes (27)

• Blood pressure

  Blood pressure responses (systolic and diastolic) to sympathoexcitation

  Baseline (pre-ingestion)

• Blood pressure

  Blood pressure responses (systolic and diastolic) to sympathoexcitation

  30 minutes post ingestion

• Blood pressure

  Blood pressure responses (systolic and diastolic) to sympathoexcitation

  45 minutes post ingestion

• Blood pressure

  Blood pressure responses (systolic and diastolic) to sympathoexcitation

  60 minutes post ingestion

• Blood pressure

  Blood pressure responses (systolic and diastolic) to sympathoexcitation

  75 minutes post ingestion

• Blood pressure

  Blood pressure responses (systolic and diastolic) to sympathoexcitation

  90 minutes post ingestion

• Blood pressure

  Blood pressure responses (systolic and diastolic) to sympathoexcitation

  105 minutes post ingestion

• Heart Rate

  Heart rate responses to sympathoexcitation

  Baseline (pre-ingestion)

• Heart Rate

  Heart rate responses to sympathoexcitation

  30 minutes post ingestion

• Heart Rate

  Heart rate responses to sympathoexcitation

  45 minutes post ingestion

• Heart Rate

  Heart rate responses to sympathoexcitation

  60 minutes post ingestion

• Heart Rate

  Heart rate responses to sympathoexcitation

  75 minutes post ingestion

• Heart Rate

  Heart rate responses to sympathoexcitation

  90 minutes post ingestion

• Heart Rate

  Heart rate responses to sympathoexcitation

  105 minutes post ingestion

• Heart Rate Variability

  Index of cardiac autonomic control

  Baseline (pre-ingestion)

• Heart Rate Variability

  Index of cardiac autonomic control

  45 post ingestion

• Cardiac Baroreflex Sensitivity

  Changes in cardiac interval relative to changes in systolic blood pressure

  105 minutes post ingestion

• Hunger - Visual Digital Analog Scale (0-100)

  Changes in subjective rating of hunger

  Baseline, 30, 45, 60, 75, 90, 105, 120 minutes post ingestion

• Fullness - Visual Digital Analog Scale (0-100)

  Changes in subjective rating of fullness

  Baseline, 30, 45, 60, 75, 90, 105, 120 minutes post ingestion

• Desire to eat - Visual Digital Analog Scale (0-100)

  Changes in subjective rating of desire to eat

  Baseline, 30, 45, 60, 75, 90, 105, 120 minutes post ingestion

• Prospective consumption of food - Visual Digital Analog Scale (0-100)

  Changes in subjective rating of prospective consumption of food

  Baseline, 30, 45, 60, 75, 90, 105, 120 minutes post ingestion

• Thirst - Visual Digital Analog Scale (0-100)

  Changes in subjective rating of thirst

  Baseline, 30, 45, 60, 75, 90, 105, 120 minutes post ingestion

• Stroop Test - Digital Cognitive Function Test

  Changes in Stroop score

  Baseline, 75 minutes

• Go/No-go Test - Digital Cognitive Function Test

  Changes in Go/No-go score

  Baseline, 75 minutes

• Task Switching Task - Digital Cognitive Function Test

  Changes in Task Switching Task score

  Baseline, 75 minutes

• Number Back Test - Digital Cognitive Function Test

  Changes in Number Back Test score

  Baseline, 75 minutes

• Digit Span Test - Digital Cognitive Function Test

  Changes in Digit Span Test score

  Baseline, 75 minutes

Secondary Outcomes (7)

• Prefrontal Cortex Oxygenation

  Baseline, 90 minutes post ingestion

• Peripheral Blood Flow

  Baseline, 30, 60 and 90 minutes post ingestion

• Peripheral Vascular Conductance

  Baseline, 30, 60 and 90 minutes post ingestion

• Blood ketones

  Baseline, 30, 60, 90, 120 minutes post ingestion

• Blood glucose

  Baseline, 30, 60, 90, 120 minutes post ingestion

Study Arms (2)

Ketone Ester

EXPERIMENTAL

Oral ketone ester supplement

Dietary Supplement: Ketone Ester Supplement

Placebo

PLACEBO COMPARATOR

Taste and viscosity matched placebo

Other: Placebo

Interventions

Ketone Ester Supplement DIETARY_SUPPLEMENT

Oral ingestion of a ketone supplement combined with a flavoring agent and diluted in water

Ketone Ester

Placebo OTHER

Oral ingestion of cellulose combined with a flavoring agent and diluted in water

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults between the ages of 18-50 years of age.
• Presence of metabolic sydnrome
• Control Participant Eligibility:
• A waist circumference of \< 102 cm for males and \< 88 cm for females, and
• No indication of metabolic syndrome

You may not qualify if:

• Pregnant
• Breastfeeding or lactating
• Missing any limbs or part of a limb
• Having a substantial amount of metal implants (metal plates or complete joint replacements)
• Having a pacemaker or any other electrical implant
• Type I diabetes
• Gestational diabetes
• Taking insulin
• Any history of severe traumatic brain injury or mild traumatic brain injury within the last two years
• Kidney disease
• Liver disease
• Thyroid disease
• Any diagnosed neurological or neurodegenerative diseases
• Any surgeries that would impact swallowing and/or digestion
• Being on a ketogenic diet or having been on a ketogenic diet in the last 6 months

Sponsors & Collaborators

• University of Southern Mississippi: lead

Study Sites (1)

University of Southern Mississippi - School of Kinesiology and Nutrition

Hattiesburg, Mississippi, 39406, United States

Location

Related Publications (1)

• Stavres J, Aultman RS, Brandner CF, Vallecillo-Bustos A, Compton AT, Swafford SH, Newsome TA, Graybeal AJ. Influence of exogenous ketosis on spontaneous cardiovagal baroreflex gain and blood pressure responses to isometric handgrip in individuals with metabolic syndrome: a placebo-controlled pilot study. Eur J Appl Physiol. 2025 Jul 31. doi: 10.1007/s00421-025-05921-z. Online ahead of print.

  PMID: 40745496 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Austin J Graybeal, PhD

  University of Southern Mississippi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 3, 2022
• First Posted: December 14, 2022
• Study Start: December 28, 2022
• Primary Completion: December 29, 2023
• Study Completion: December 29, 2023
• Last Updated: May 22, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)