Markers of Appetite Regulation During Exogenous Ketosis

Study Overview
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Brief Summary
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The aim of this study is to investigate the relationship, if any, between markers of satiety, desire to eat, hunger, and metabolic markers of the regulation hereof during ketosis as compared with a Glucose-containing and a Placebo drink adjusted for taste.

Detailed Description
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All subjects are, in random order, tested on three separate occasions with intake of weight adjusted and taste matched drink of i) a ketone ester, and ii) an isocaloric and -volumetric glucose drink, or iii) an isovolumetric tap water drink. Subjects are studied for five hours with baseline and blood sampling on multiple occasions. A satiety questionaire are included. Subjects are recruited through notice on website for this purpose. Sample size calculations were performed prior to inclusion (n=10). According to protocolized statistical plan, missing data will not be replaced and no imputation will occur. Data will be analyzed by applying a repeated measurements multilevel model with intervention, time and their interactions as categorical factors. Effects size are adjusted for small sample size.

Official Title
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Markers of Appetite Regulation During Exogenous Ketosis - a Placebo Controlled Randomized Study of Appetite Regulatory and Metabolic Markers After Intake of a Keto- or Glucogenic Drink.

Conditions
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Ketosis

Intervention / Treatment
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* Dietary Supplement: Ketone ester
* Dietary Supplement: Glucose
* Dietary Supplement: Tap water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males aged 18-65 years BMI 20-35 kg/m2 Expected ease of catheter insertion Oral and written informed consent Exclusion Criteria: Inability to fully understand the consent including consent forms Inability to cooperate to the trial Any electrolyte disorders, kidney disease or otherwise compromised renal function including excess risk hereof, e.g. hypertension, albuminuria, autoimmune disease, family history of kidney disease Any liver or bile disease including excess risk hereof, e.g. hepatotoxic drugs, alcohol abuse disorder, gallstones, pancreatitis, autoimmune disease, family history of liver disease Diabetes mellitus or any metabolic and/or hormonal disease including diagnosed/undiagnosed reactive hypoglycemia or similar disorders. This includes treatment with drugs, dietary supplement with inference on key metabolic or hormonal markers, e.g. insulin, glukagon, lipids, and GLP-1 Any use of illegal or otherwise use of medicinal products without prescription Anemia or other know disease of the hematopoietic system Previous bariatric surgery Previous myocardial infarction or uncontrolled myocardial ischemia Recent intended/unintended weight loss Allergies to catheters or adhesives

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a experimental, randomized, single-center cross-over study.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketone ester<br>Intake of a ketogenic drink. | Dietary Supplement: Ketone ester<br>* Intake of weight adjusted drink of a ketone ester<br>|
| Active Comparator: Isocaloric and -volumetric glucose drink<br>Intake of a taste matched glucogenic drink. | Dietary Supplement: Glucose<br>* Isocaloric and - volumetric taste adjusted drink<br>|
| Placebo Comparator: Isovolumetric tap water drink<br>Intake of a taste matched tap water drink. | Dietary Supplement: Tap water<br>* Isovolumetric taste adjusted tap water (placebo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GLP-1 concentration | Development of GLP-1 concentration during ketosis as compared after intake of a ketogenic vs a glucogenic drink vs a control drink, respectively. | 5 hours | 
| Acyl ghrelin concentration | Development of acyl ghrelin concentration during ketosis as compared after intake of a ketogenic vs a glucogenic drink vs a control drink, respectively. | 5 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Satiety, desire to eat, and perceived hunger sensation | Scores of satiety, desire to eat, and perceived hunger sensation during intervention all measured on a scale from 1-100 where 1 is the lowest score and 100 the highest. | 5 hours | 
| Glucose concentration | Development of glucose concentration during ketosis as compared after intake of a ketogenic vs a glucogenic drink vs a control drink, respectively. | 5 hours | 
| Insulin concentration | Development of insulin concentration during ketosis as compared after intake of a ketogenic vs a glucogenic drink vs a control drink, respectively. | 5 hours | 
| Free fatty acids concentration | Development of free fatty acids concentration during ketosis as compared after intake of a ketogenic vs a glucogenic drink vs a control drink, respectively. | 5 hours |