β-hydroxybutyrate, Glucose Metabolism and Prediabetes

Study Overview
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Brief Summary
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The study aims to investigate changes in blood glucose metabolism after administration of a ketone ester drink.

Detailed Description
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New-onset prediabetes is the most significant risk factor for diabetes. Clinical studies in healthy human volunteers have demonstrated that ketone esters lower blood glucose levels in both fasting and fed state. Participants will visit the COSMOS clinic on two occasions and will be randomly allocated to receive either the HVMN ketone drink or placebo, in a cross-over design. Blood samples will be collected sequentially every 30 minutes for up to 150 minutes. Blood samples will be assayed for glucose and other markers of glucose metabolism.

Official Title
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Cross-over, Placebo-controlled, Randomized Trial of β-hydroxybutyrate in Prediabetes

Conditions
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PreDiabetes

Intervention / Treatment
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* Other: HVMN Ketone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals over 18 years Individuals diagnosed with prediabetes; defined based on the American Diabetes Association guidelines History of at least one episode of acute pancreatitis Written informed consent Exclusion Criteria: Individuals who are on a ketogenic diet or consuming nutritional ketone supplements History of cancer or chronic pancreatitis History of bariatric or gastrointestinal surgery Pregnant or breastfeeding women Individuals involved in intensive endurance training or competitive athletics

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HVMN ketone drink<br>HVMN ketone drink will be given in a total volume of 100 ml. | Other: HVMN Ketone<br>* Water-based, flavoured sport beverage<br>|
| Placebo Comparator: Placebo<br>Placebo will be given in a total volume of 100 ml. | Other: Placebo<br>* Water, stevia, malic acid, and thickening agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of change in plasma glucose concentration | Changes in plasma glucose concentration before and after administration of the intervention/placebo | Baseline, 30, 60, 90, 120, and 150 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of change in plasma insulin and C-peptide concentrations | Changes in plasma insulin and C-peptide concentrations before and after administration of the intervention/placebo | Baseline, 30, 60, 90, 120, and 150 minutes | 
| Rate of change in plasma concentration of gut and pancreatic hormones | Changes in plasma concentrations of ghrelin, incretins, cholecystokinin, gastrin-releasing peptide, peptide YY, oxyntomodulin, motilin, glucagon, amylin, pancreatic polypeptide, and vasoactive intestinal peptide before and after administration of the intervention/placebo | Baseline, 30, 60, 90, 120, and 150 minutes | 
| Rate of change in lipid profile and digestive enzymes | Changes in plasma concentration of triglycerides, glycerol, cholesterol, lipases before and after administration of the intervention/placebo | Baseline, 30, 60, 90, 120, and 150 minutes | 
| Rate of change in plasma concentration of pro-inflammatory cytokines | Changes in plasma concentration of interleukin-1β, interleukin-6, leptin, tumor necrosis factor α, and monocyte chemoattractant protein-1 and other cytokines before and after administration of the intervention/placebo | Baseline, 30, 60, 90, 120, and 150 minutes | 
| Rate of change in plasma concentration of markers of iron metabolism | Changes in plasma concentration of ferritin, hepcidin, transferrin receptor before and after administration of the intervention/placebo | Baseline, 30, 60, 90, 120, and 150 minutes | 
| Correlation with body fat phenotypes | Differences in the association between rate of change in plasma glucose concentration and magnetic resonance imaging-derived visceral fat volume in the intervention/placebo | 150 minutes | 
| Correlation with body fat phenotypes | Differences in the association between rate of change in plasma glucose concentration and magnetic resonance imaging-derived subcutaneous fat volume in the intervention/placebo | 150 minutes | 
| Correlation with body fat phenotypes | Differences in the association between rate of change in plasma glucose concentration and magnetic resonance imaging-derived liver fat per centage in the intervention/placebo | 150 minutes | 
| Correlation with physical activity | Differences in the association between rate of change in plasma glucose concentration and metabolic equivalents score in the intervention/placebo | 150 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketones, Prediabetes