Markers of Appetite Regulation During Exogenous Ketosis (MARK)

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.

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.

Study Overview

• Status: Unknown
• Conditions: Ketosis
• Intervention / Treatment: Dietary supplement: Ketone ester; Dietary supplement: Glucose; Dietary supplement: Tap water

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Viborg, Denmark, 8800
    • Regionshospitalet Viborg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Central Jutland Regional Hospital
• Investigators: Principal Investigator: Henrik H Thomsen, M.D., PhD, Viborg Region Hospital, Central Jutland

Publications and helpful links

General Publications

• Myette-Cote E, Neudorf H, Rafiei H, Clarke K, Little JP. Prior ingestion of exogenous ketone monoester attenuates the glycaemic response to an oral glucose tolerance test in healthy young individuals. J Physiol. 2018 Apr 15;596(8):1385-1395. doi: 10.1113/JP275709. Epub 2018 Mar 2. Erratum In: J Physiol. 2019 Nov;597(22):5515. Abstract corrected.
• Stubbs BJ, Cox PJ, Evans RD, Santer P, Miller JJ, Faull OK, Magor-Elliott S, Hiyama S, Stirling M, Clarke K. On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 2017 Oct 30;8:848. doi: 10.3389/fphys.2017.00848. eCollection 2017.
• Laeger T, Metges CC, Kuhla B. Role of beta-hydroxybutyric acid in the central regulation of energy balance. Appetite. 2010 Jun;54(3):450-5. doi: 10.1016/j.appet.2010.04.005. Epub 2010 Apr 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2019
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 7, 2019

Study Record Updates

• Last Update Posted (Actual): November 15, 2019
• Last Update Submitted That Met QC Criteria: November 14, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Acidosis; Ketosis
• Other Study ID Numbers: 121953

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No