Echocardiographic Changes After 3-hydroxy Butyrate+Whey Intake

Echocardiography Clinical Trial

Official title:

Echocardiographic Changes After Oral Intake of 3-hydroxy Butyrate+Whey in a Human Endotoxemia Model

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04037722
• Other study ID #: Ketone Heart Study
• Status: Completed
• Phase: N/A
• Start date: June 17, 2019
• Est. completion date: January 23, 2020

Study information

• Verified date: July 2019
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: January 23, 2020
• Est. primary completion date: January 23, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Output
• Catabolic State
• Echocardiography
• Endotoxemia

Intervention

Dietary Supplement:
• Whey
45 g whey + 20 g maltodextrin
• 3-OHB + Whey
50 g ketone + 45 g whey + 20 g maltodextrin

Locations

Country	Name	City	State
Denmark	Medical Research Labarotory, DoH, Aarhus University Hospital	Aarhus

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital Skejby, Arla Food Ingredients, Arla Viby.

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in left ventricular outflow tract velocity time integral	Echocardiographic changes in left ventricular outflow tract velocity time integral from the basal period and after 1.5 hours of intervention	Measured during the basal period and after 1.5 hours of intervention
Secondary	Changes in Left Ventricular Ejection Fraction (LVEF)	Echocardiographic changes in LVEF from the basal period and after 1.5 hours of intervention	Measured during the basal period and after 1.5 hours of intervention
Secondary	Changes in Global Longitudinal Strain (GLS)	Echocardiographic changes in GLS from the basal period and after 1.5 hours of intervention	Measured during the basal period and after 1.5 hours of intervention
Secondary	Changes in S´ Max	Echocardiographic changes in S´ Max from the basal period and after 1.5 hours of intervention	Measured during the basal period and after 1.5 hours of intervention
Secondary	Changes in blood pressure	Changes in blood pressure from the basal period and after 1.5 hours of intervention	Measured during the basal period and after 1.5 hours of intervention
Secondary	Changes in heart rate	Changes in heart rate from the basal period and after 1.5 hours of intervention	Measured during the basal period and after 1.5 hours of intervention
Secondary	Changes in axillary temperature	Changes in axillary temperature from the basal period and after 1.5 hours of intervention	Measured during the basal period and after 1.5 hours of intervention
Secondary	Difference in Left Ventricular Ejection Fraction (LVEF) (Healthy vs catabolic conditions)	Echocardiographic difference in LVEF during the basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)	Measured after 2 hours of basal period
Secondary	Difference in Global Longitudinal Strain (GLS) (Healthy vs catabolic conditions)	Echocardiographic difference in GLS during the basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)	Measured after 2 hours of basal period
Secondary	Difference in S´ Max (Healthy vs catabolic conditions)	Echocardiographic difference in S´ Max during the basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)	Measured after 2 hours of basal period
Secondary	Difference in axillary temperature (healthy vs catabolic)	Difference in axillary temperature after 2 hours basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)	Measured after 2 hours of basal period
Secondary	Difference in heart rate (healthy vs catabolic)	Difference in heart rate after 2 hours basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)	Measured after 2 hours of basal period
Secondary	Difference in blood pressure (healthy vs catabolic)	Difference in blood pressure after 2 hours basal period between healthy and catabolic conditions (a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)	Measured after 2 hours of basal period