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

Study Overview
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Brief Summary
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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.

Official Title
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Non-pharmacological Treatments for Obesity: Leveraging the Appetite Suppressive Effects of Hyperketonemia Through Exogenous Ketone Ingestion to Treat Obesity, Insulin Resistance, and Cognition

Conditions
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Obesity, Pre Diabetes, Diabetes Mellitus, Type 2, Insulin Resistance

Intervention / Treatment
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* Dietary Supplement: Ketone Ester Supplement
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults between the ages of 18-50 years of age. Presence of one of the following: Body mass index (BMI) of = 30 kg/m2; a waist circumference of = 102 cm for males and = 88 cm for females Body fat percentage of = 28% for males and = 40% for females. The additional presence of one of the following: Fasting blood glucose of 100-125 mg/dl indicating prediabetes Fasting blood glucose of 126 mg/dl or greater indicating undiagnosed diabetes Previously diagnosed type II diabetes that is not insulin-dependent. Control Participant Eligibility: Normal weight (BMI < 25.00 kg/m2) A waist circumference of < 102 cm for males and < 88 cm for females, and No indication of diabetes based on the aforementioned criteria Exclusion Criteria: 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 Having received ionizing radiation from a medical procedure within the last 30 days Being on a medically prescribed diet

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketone Ester<br>Oral ketone ester supplement | Dietary Supplement: Ketone Ester Supplement<br>* Oral ingestion of a ketone supplement combined with a flavoring agent and diluted in water<br>|
| Placebo Comparator: Placebo<br>Taste and viscosity matched placebo | Other: Placebo<br>* Oral ingestion of cellulose combined with a flavoring agent and diluted in water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prefrontal Cortex Oxygenation | Near-infrared spectroscopy | Baseline, 90 minutes post ingestion | 
| Peripheral Blood Flow | Doppler Ultrasound of Femoral Artery | Baseline, 30, 60 and 90 minutes post ingestion | 
| Peripheral Vascular Conductance | Blood flow normalized to blood pressure (mL/min/mmHg) | Baseline, 30, 60 and 90 minutes post ingestion | 
| Blood ketones | Ketone body level from capillary blood | Baseline, 30, 60, 90, 120 minutes post ingestion | 
| Blood glucose | Blood glucose level from capillary blood | Baseline, 30, 60, 90, 120 minutes post ingestion | 
| Oxygen Consumption from Respiratory Gases | Amount of oxygen consumed using indirect calorimetry | Baseline and continuous for 120 minutes | 
| Carbon Dioxide Produced from Respiratory Gases | Amount of carbon dioxide produced using indirect calorimetry | Baseline and continuous for 120 minutes |