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Assessment of BHB Concentration Agreement Among Sampling Locations and the Impact of Ketosis on EPO, and More

Primary Purpose

Ketosis

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Ketone monoester
Placebo
Sponsored by
Central Jutland Regional Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Ketosis focused on measuring ketosis, ketone monoester, erythropoitin, sex hormones

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Age 18-60 years BMI 19-30 kg/m2 Expected ease of catheter insertion Considered of sound health Oral and written informed consent Exclusion Criteria: Inability to fully understand the consent including consent forms Inability to cooperate to the study electrolyte disorders acute or chronic kidney disease or ompromised renal function including excess risk servere hypertension autoimmune disease liver or bile disease diabetes mellitus reactive hypoglycemia or similar disorders treatment with drugs, and dietary supplements with inference on key metabolic or hormonal markers, e.g. insulin, glucagon, DDP-IV inhibitors, GLP-1 RA, sulfunylurea 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

Sites / Locations

  • Department of Internal Medicine, Viborg Regional HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ketosis

Control

Arm Description

Ketosis (the condition being investigated) is obtained by ingestion of a ketone monoester

The control arm is a drink matched in taste, volume, appearence, and viscosity to that of the active/experimental arm

Outcomes

Primary Outcome Measures

Plasma Beta-hydroxybutyrate (BHB)
The levels of BHB were measured using the Ketosure POCT device, with samples taken from capillary blood (finger pulp and earlobes) and venous plasma. Plasma-BHB was also measured using LCMS on venous blood samples. Measured and reported in mmol/L (millimoles per liter)
Erythropoietin (EPO)
EPO concentrations measured in blood samples on standard hospital laboratory equipment. Measured and reported in IU/L (international units per liter)
Testosterone
Measured in venous plasma. Measured and reported in nmol/L (nanomoles per liter) pmol/L (picomoles per liter) for estradiol
Aldosterone
Hemodynmiac and blood pressure regulating hormones measured in plasma. Measured and reported in standard units: pmol/L (picomoles per liter), renin in mIU/L (milli international units per liter), proBNP in ng/L (nanogram per liter)
Estradiol
Measured in pmol/L (picomoles per liter) in venous plasma
Renin
Venous plasma, reported in mIU/L (milli international units per liter)
ProBNP
Measured in venous plasma and reported in ng/L (nanogram per liter). proBNP=pro brain natriuretic peptide

Secondary Outcome Measures

Full Information

First Posted
August 23, 2023
Last Updated
September 19, 2023
Sponsor
Central Jutland Regional Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06053138
Brief Title
Assessment of BHB Concentration Agreement Among Sampling Locations and the Impact of Ketosis on EPO, and More
Official Title
Assessment of BHB Concentration Agreement Among Sampling Locations and the Impact of Ketosis on Erythropoietin Levels: A Two-Part Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 24, 2023 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Central Jutland Regional Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
his study aims to address two key aspects - part 1: the suitability of selecting a specific sampling site for BHB measurement in patients and research, as well as potential differences between capillary and venous blood measurements. Additionally, the study will delve into the effects of ketosis on EPO concentrations, sex hormones levels, and hemodynamic markers and blood pressure - part 2. This investigation will utilize blood samples collected during part 1, including acute effects, as well as samples taken on day 7 and day 14 during which period participants are exposed to intermittent ketosis.
Detailed Description
Aim and Perspective: The primary objective of this study - part 1 - is to ascertain: The agreement between estimates of beta-hydroxybutyrate (BHB) in capillary and venous blood and whether this agreement is influenced by the level of BHB. The agreement in BHB measurements between finger and earlobe capillary samples. The agreement in BHB measurements between venous estimates obtained through a point-of-care device (KetoSure) and full blood estimates obtained through hydrophilic interaction liquid chromatography tandem mass spectrometry (HLCMS). The central aim of the study - part 2 - is to investigate: The impact of ketosis on short-term and long-term erythropoietin (EPO) levels. The resulting effects of EPO on erythropoiesis and iron metabolism during a two-week period of intermittent ketosis. The effects of ketosis and sex hormones including derived factors The effects of ketosis on hemodynamic markers and blood pressure The study aims to determine the appropriateness of selecting a specific sampling site for BHB measurement in both patient care and research. Additionally, it seeks to identify any differences between BHB measurements from capillary and venous blood samples. The study will also examine the concordance between the KetoSure point-of-care-test (POCT) device and the established gold standard, offering insight into any discrepancies arising from electrochemical estimations and HLCMS. Accurate BHB measurement is crucial in clinical and experimental settings. Firstly, precise BHB quantification can inform clinical decision-making for conditions such as suspected hyperinsulinemia, uncertain etiology hypoglycemia, and diabetic ketoacidosis. Secondly, given the extensive research on BHB inference and ketones in recent years, the credibility of these studies heavily hinges on the precision of measurements concerning sample type and sampling site selection. Additionally, during part 2 of the study, the effects of ketosis on EPO concentrations, sex hormone levels, hemodynamic markers, and blood pressure measurements will be explored. These analyses will be conducted using blood samples collected during part 1 (acute effects) as well as on day 7 and day 14, when participants experience intermittent ketosis. Analytical Approach: Following a visual assessment of graphical linearity representation, differences will be calculated using the paired t-test, agreement determined using the Bland-Altman plot, and correlations assessed using Pearson's r. Further calculations will employ Lin's concordance correlation coefficient of absolute agreement. For comparisons across observations in parts 1 and 2, an analysis equivalent to repeated measurements ANOVA will be applied. No imputation of missing data will be conducted, and steps will be taken to ensure data completeness before participants leave the research facilities. Sample Size and Power Calculation: Given the absence of prior studies on BHB agreement data, our study's sample size calculations are based on relevant literature. Citing Boyd et al., and considering correlated glucose estimates, a sample size of 13 participants will provide sufficient statistical power (alpha = 0.05, beta = 20%) to detect a difference of 0.58 mM in glucose estimates between capillary and venous blood samples (SD = 0.68 mM). A sample size of 20 participants is justifiably required to detect a clinically significant difference of 1 mM (SD = 1.5) under the same parameters. Consequently, we will include 16 patients in our study, aligning with similar projects and justified sample size for part 2. Collection of New Biological Material: A total of 150 mL of blood will be drawn, including incidental spillage from repeated sampling through an indwelling catheter in part 1. No spillage is expected in part 2 as blood sampling occurs only twice in an outpatient setting, with subsequent laboratory analysis. Purpose of Storage: All biological samples will be stored for the entire data collection period and 18 months thereafter for bulk analysis. Storage will be at -80 ºC. A research biobank will be established to analyze samples not analyzed on the study day, with surplus material preserved for future research. Handling of Patient Information: Access to participants' electronic patient records, limited to the laboratory results section, is included in the consent for practical reasons. Only routinely obtained treatment-related information necessary for analysis will be accessed. Any information obtained before consent will be shared with the investigator. Data Privacy and Sharing: Data will be pseudonymized during analysis, with de-identification codes retained by the primary investigator. Data access will be restricted to investigators until final analysis. Upon anonymization, other investigators will gain access. After publication, all data will be open accesible upon reasonably request. However, consideration to make data available to public scrutiny is under consideration. Financial Information: The study is initiated and financed by the primary investigator, Henrik Holm Thomsen. Funding originates from independent research funds within the Department of Internal Medicine, Regional Hospital Viborg. Additional external funding will be pursued for study expenses only, excluding investigator salaries. Financial transactions follow the research practices of the Central Denmark Region and Regional Hospital Viborg. Research investigators and collaborators have no financial interests in the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ketosis
Keywords
ketosis, ketone monoester, erythropoitin, sex hormones

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Participants are all exposed to the intervention (ketosis) in part 1 followed by randomization to either active intervention (ketosis) or placebo in part 2 of the study
Masking
ParticipantCare ProviderInvestigator
Masking Description
Participants are blinded to the drink (intervention) being either ketosis (obtained by ingestion of a ketone monoester drink) or plaacebo (a tate and volume matched drink). Drinks are provided in similar neutral unlabelled bottles
Allocation
Randomized
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ketosis
Arm Type
Experimental
Arm Description
Ketosis (the condition being investigated) is obtained by ingestion of a ketone monoester
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
The control arm is a drink matched in taste, volume, appearence, and viscosity to that of the active/experimental arm
Intervention Type
Dietary Supplement
Intervention Name(s)
Ketone monoester
Other Intervention Name(s)
KetoneAid Ke4 Pro Ketone Ester
Intervention Description
Supraphysiological levels of ketosis acutely, part 1, and intermittently and longer lasting, part 2, as obtained by ingestion of a ketone monoester dietary supplement
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
The placebo vehicle is matched to the ketosis intervention in the experimental arm with regards to taste, volume, viscosity, appearence, and packaging
Primary Outcome Measure Information:
Title
Plasma Beta-hydroxybutyrate (BHB)
Description
The levels of BHB were measured using the Ketosure POCT device, with samples taken from capillary blood (finger pulp and earlobes) and venous plasma. Plasma-BHB was also measured using LCMS on venous blood samples. Measured and reported in mmol/L (millimoles per liter)
Time Frame
Baseline (0 minutes), 30, 60, 90, 120, 150, and 180 minutes(part 1) and at Day 8 and Day 15 (part 2)
Title
Erythropoietin (EPO)
Description
EPO concentrations measured in blood samples on standard hospital laboratory equipment. Measured and reported in IU/L (international units per liter)
Time Frame
Baseline (0 minutes),60, 90, 150, and 180 minutes(part 1) and at Day 8 and Day 15 (part 2)
Title
Testosterone
Description
Measured in venous plasma. Measured and reported in nmol/L (nanomoles per liter) pmol/L (picomoles per liter) for estradiol
Time Frame
Baseline (0 minutes), 90, and 180 minutes(part 1) and at Day 8 and Day 15 (part 2)
Title
Aldosterone
Description
Hemodynmiac and blood pressure regulating hormones measured in plasma. Measured and reported in standard units: pmol/L (picomoles per liter), renin in mIU/L (milli international units per liter), proBNP in ng/L (nanogram per liter)
Time Frame
Baseline (0 minutes), 90, and 180 minutes (part 1) and at Day 8 and Day 15 (part 2)
Title
Estradiol
Description
Measured in pmol/L (picomoles per liter) in venous plasma
Time Frame
Baseline (0 minutes), 90, and 180 minutes (part 1) and at Day 8 and Day 15 (part 2)
Title
Renin
Description
Venous plasma, reported in mIU/L (milli international units per liter)
Time Frame
Baseline (0 minutes), 90, and 180 minutes (part 1) and at Day 8 and Day 15 (part 2)
Title
ProBNP
Description
Measured in venous plasma and reported in ng/L (nanogram per liter). proBNP=pro brain natriuretic peptide
Time Frame
Baseline (0 minutes), 90, and 180 minutes (part 1) and at Day 8 and Day 15 (part 2)
Other Pre-specified Outcome Measures:
Title
Hematocrit
Description
hematocrit - percentages mean corpuscular volume - fmol (femtomoles) ferritin - microgram/L transferrin - microgram/L Measured and reported in standard units
Time Frame
Baseline (0 minutes), 90, and 180 minutes(part 1) and at Day 8 and Day 15 (part 2)
Title
Hemoglobin
Description
hemoglobin - mmol/L hematocrit - percentages hemoglobin - mmol/L erythrocytes - x10^12/L leukocytes - x10^12/L mean corpuscular volume - fmol (femtomoles) ferritin - microgram/L transferrin - microgram/L Measured and reported in standard units
Time Frame
Baseline (0 minutes), 90, and 180 minutes(part 1) and at Day 8 and Day 15 (part 2)
Title
Erythrocytes
Description
erythrocytes - x10^12/L hematocrit - percentages hemoglobin - mmol/L erythrocytes - x10^12/L leukocytes - x10^12/L mean corpuscular volume - fmol (femtomoles) ferritin - microgram/L transferrin - microgram/L Measured and reported in standard units
Time Frame
Baseline (0 minutes), 90, and 180 minutes(part 1) and at Day 8 and Day 15 (part 2)
Title
Leukocytes
Description
leukocytes - x10^12/L hematocrit - percentages hemoglobin - mmol/L erythrocytes - x10^12/L leukocytes - x10^12/L mean corpuscular volume - fmol (femtomoles) ferritin - microgram/L transferrin - microgram/L Measured and reported in standard units
Time Frame
Baseline (0 minutes), 90, and 180 minutes(part 1) and at Day 8 and Day 15 (part 2)
Title
Mean corpuscular volume
Description
mean corpuscular volume - fmol (femtomoles) hematocrit - percentages hemoglobin - mmol/L erythrocytes - x10^12/L leukocytes - x10^12/L mean corpuscular volume - fmol (femtomoles) ferritin - microgram/L transferrin - microgram/L Measured and reported in standard units
Time Frame
Baseline (0 minutes), 90, and 180 minutes(part 1) and at Day 8 and Day 15 (part 2)
Title
Lutropin
Description
lutropin - IU/L (international units per liter)
Time Frame
Baseline (0 minutes), 90, and 180 minutes(part 1) and at Day 8 and Day 15 (part 2)
Title
Follitropin
Description
follitropin - IU/L
Time Frame
Baseline (0 minutes), 90, and 180 minutes(part 1) and at Day 8 and Day 15 (part 2)
Title
Home blood pressure measurements
Description
Study participants record their home blood pressure and heart rate, both systolic and diastolic, with provided automated blod pressure measurement devices in accordance with guidelines. Blood pressure is estimated and reported in mmHg
Time Frame
Measurements are made just prior to Day 8 and Day 15 in addition to measurements in Study part 1 made by research staff
Title
Heart rate
Description
heart rate measured in beats per minut with the blood pressure monitor that also counts the heart rate
Time Frame
Measurements are made just prior to Day 8 and Day 15 in addition to measurements in Study part 1 made by research staff

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age 18-60 years BMI 19-30 kg/m2 Expected ease of catheter insertion Considered of sound health Oral and written informed consent Exclusion Criteria: Inability to fully understand the consent including consent forms Inability to cooperate to the study electrolyte disorders acute or chronic kidney disease or ompromised renal function including excess risk servere hypertension autoimmune disease liver or bile disease diabetes mellitus reactive hypoglycemia or similar disorders treatment with drugs, and dietary supplements with inference on key metabolic or hormonal markers, e.g. insulin, glucagon, DDP-IV inhibitors, GLP-1 RA, sulfunylurea 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Henrik H Thomsen, Ph.D.
Phone
+4550721835
Email
henrik.holm.thomsen@midt.rm.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Henning B Danielsen, Ph.D.
Phone
+4578447000
Email
Henning.Danielsen@midt.rm.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henrik H Thomsen, Ph.D.
Organizational Affiliation
Department of Internal Medicine, Viborg Regional Hospital, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Internal Medicine, Viborg Regional Hospital
City
Viborg
ZIP/Postal Code
8800
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henrik H Thomsen, Ph.D.
Phone
+4550721835
Email
henrik.holm.thomsen@midt.rm.dk
First Name & Middle Initial & Last Name & Degree
Henning B Danielsen, Ph.D.
Phone
+4578447000
Email
Henning.Danielsen@midt.rm.dk
First Name & Middle Initial & Last Name & Degree
Birgitte S Paulsen, Ph.D.
First Name & Middle Initial & Last Name & Degree
Lise N Bjerg

12. IPD Sharing Statement

Plan to Share IPD
No

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Assessment of BHB Concentration Agreement Among Sampling Locations and the Impact of Ketosis on EPO, and More

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