Clinical trial NCT04037722: Echocardiographic Changes After 3-hydroxy Butyrate+Whey Intake
Official title: Echocardiographic Changes After Oral Intake of 3-hydroxy Butyrate+Whey in a Human Endotoxemia Model
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiac Output
Endotoxemia
Catabolic State
Echocardiography
Keywords: Cardiac Output
Endotoxemia
Ketone bodies
3-hydroxy butyrate
Whey protein
Catabolic State
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Arla Food Ingredients, Arla Viby.
name: Aarhus University Hospital Skejby
First posted: 2019-07-30
Enrollment: 8
Sex: MALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: In a randomized crossover design, eight healthy lean young men will undergo either:

i) Healthy conditions (overnight fast) + whey protein

ii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest) + whey protein

iii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest) + 3-OHB/whey protein
Primary purpose: BASIC_SCIENCE

Brief summary: This study evaluates the cardiovascular effects of adding the ketone body 3-hydroxy butyrate (3-OHB) to whey protein during human endotoxemia. Further, this study compares cardiovascular changes during healthy and catabolic conditions.

Participants will receive isocaloric, isonitrogenous beverages of either whey or 3-OHB+whey in a randomized crossover design during either healthy (overnight fast) or catabolic conditions (inflammation/endotoxemia + 36 h fast and bed rest).

Detailed description: Background: A newly published study found beneficial cardiovascular effects of 3-OHB infusion in a population with chronic heart failure, significantly increasing cardiac output. Similar effects on cardiac output were observed in healthy volunteers. These findings pave the way for 3-OHB as a therapeutic nutritional supplement, since it is well-absorbed during oral consumption. However, it is unknown whether the cardiovascular effects of 3-OHB persist during a sepsis-like catabolic state and when administered orally.

Aim: This study aims to investigate the cardiovascular effects of adding the ketone body 3-hydroxy butyrate (3-OHB) to whey protein during a human disease model, comprising endotoxemia + bed rest + fast.

Hypothesis:

1. Adding the ketone body 3-OHB to an oral protein supplement increases cardiac output measures
2. Catabolic stress (endotoxemia/inflammation + 36 h fast and bed rest) induces cardiovascular changes compared with healthy conditions (overnight fast)

   Interventions:

   In a randomized crossover design, eight healthy, lean, young men will undergo either:

   i) Healthy conditions (overnight fast) + whey protein\^

   ii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest\*) + whey protein\^

   iii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest\*) + 3-OHB/whey protein\^"

   \*LPS will be administered (1 ng/kg) the day prior to the study together with fast and bed rest. On the study day LPS (0.5 ng/kg) will be injected.

   \^Beverages will be isonitrogenous and isocaloric (fat will be added) with 45 g whey protein + 20 g maltodextrin. Bolus/sip administration will be applied (1/3 bolus, 1/2 sip)

   " 50 grams of 3-OHB will be orally administered (1/2 bolus, 1/2 sip)

Eligibility criteria: Inclusion Criteria:

* Between 20-40 years of age
* Body mass index between 20-30 kg/m\^2
* Healthy
* Oral and written consent forms obtained prior to study day

Exclusion Criteria:

* Recent immobilization of an extremity that is not fully rehabilitated
* Lactose, lidocain or rubber allergies
* Current disease
* Use of anabolic steroids
* Smoking
* Former major abdominal surgery (Or current problems with the GI tract)

  •\>10 hours of exercise/weak
* Present ketogenic diets or high-protein diets
* Blood doner that does not want to discontinue blood donations until study completion
* Pending MR scan

Primary outcomes:
measure: Change in left ventricular outflow tract velocity time integral
timeFrame: Measured during the basal period and after 1.5 hours of intervention
Secondary outcomes:
measure: Changes in Left Ventricular Ejection Fraction (LVEF)
timeFrame: Measured during the basal period and after 1.5 hours of intervention
measure: Changes in Global Longitudinal Strain (GLS)
timeFrame: Measured during the basal period and after 1.5 hours of intervention
measure: Changes in S´ Max
timeFrame: Measured during the basal period and after 1.5 hours of intervention
measure: Changes in blood pressure
timeFrame: Measured during the basal period and after 1.5 hours of intervention
measure: Changes in heart rate
timeFrame: Measured during the basal period and after 1.5 hours of intervention
measure: Changes in axillary temperature
timeFrame: Measured during the basal period and after 1.5 hours of intervention
measure: Difference in Left Ventricular Ejection Fraction (LVEF) (Healthy vs catabolic conditions)
timeFrame: Measured after 2 hours of basal period
measure: Difference in Global Longitudinal Strain (GLS) (Healthy vs catabolic conditions)
timeFrame: Measured after 2 hours of basal period
measure: Difference in S´ Max (Healthy vs catabolic conditions)
timeFrame: Measured after 2 hours of basal period
measure: Difference in axillary temperature (healthy vs catabolic)
timeFrame: Measured after 2 hours of basal period
measure: Difference in heart rate (healthy vs catabolic)
timeFrame: Measured after 2 hours of basal period
measure: Difference in blood pressure (healthy vs catabolic)
timeFrame: Measured after 2 hours of basal period
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Medical Research Labarotory, DoH, Aarhus University Hospital
Study officials:
affiliation: Aarhus University Hospital and Institute of Clinical Medicine
name: Niels Moeller, Professor
role: PRINCIPAL_INVESTIGATOR
References: