Echocardiographic Changes After 3-hydroxy Butyrate+Whey Intake

Not Applicable

Completed

• Conditions: Cardiac Output; Endotoxemia; Catabolic State; Echocardiography
• Interventions: Dietary Supplement: Whey; Dietary Supplement: 3-OHB + Whey

• Registration Number: NCT04037722
• Lead Sponsor: University of Aarhus

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)

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2019-06-17
• Status Verified: 2019-07
• Study First Submitted: 2019-07-11
• Study First Submitted QC: 2019-07-29
• Study First Posted: 2019-07-30
• Primary Completion: 2020-01-23
• Study Completion: 2020-01-23
• Last Update Submitted: 2020-06-09
• Last Update Posted: 2020-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 8

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Healthy + Whey	Whey	Healthy conditions (overnight fast)
Catabolic + Whey	Whey	Catabolic conditions (36-hour fast, bed rest and inflammation (LPS))
Catabolic + 3-OHB / Whey	3-OHB + Whey	Catabolic conditions (36-hour fast, bed rest and inflammation (LPS))

Primary Outcome Measures

Name	Time	Method
Change in left ventricular outflow tract velocity time integral	Measured during the basal period and after 1.5 hours of intervention	Echocardiographic changes in left ventricular outflow tract velocity time integral from the basal period and after 1.5 hours of intervention

Secondary Outcome Measures

Name	Time	Method
Changes in Left Ventricular Ejection Fraction (LVEF)	Measured during the basal period and after 1.5 hours of intervention	Echocardiographic changes in LVEF from the basal period and after 1.5 hours of intervention
Changes in Global Longitudinal Strain (GLS)	Measured during the basal period and after 1.5 hours of intervention	Echocardiographic changes in GLS from the basal period and after 1.5 hours of intervention
Changes in heart rate	Measured during the basal period and after 1.5 hours of intervention	Changes in heart rate from the basal period and after 1.5 hours of intervention
Changes in S´ Max	Measured during the basal period and after 1.5 hours of intervention	Echocardiographic changes in S´ Max from the basal period and after 1.5 hours of intervention
Changes in blood pressure	Measured during the basal period and after 1.5 hours of intervention	Changes in blood pressure from the basal period and after 1.5 hours of intervention
Changes in axillary temperature	Measured during the basal period and after 1.5 hours of intervention	Changes in axillary temperature from the basal period and after 1.5 hours of intervention
Difference in Left Ventricular Ejection Fraction (LVEF) (Healthy vs catabolic conditions)	Measured after 2 hours of basal period	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)
Difference in S´ Max (Healthy vs catabolic conditions)	Measured after 2 hours of basal period	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)
Difference in Global Longitudinal Strain (GLS) (Healthy vs catabolic conditions)	Measured after 2 hours of basal period	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)
Difference in axillary temperature (healthy vs catabolic)	Measured after 2 hours of basal period	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)
Difference in blood pressure (healthy vs catabolic)	Measured after 2 hours of basal period	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)
Difference in heart rate (healthy vs catabolic)	Measured after 2 hours of basal period	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)

Trial Locations

Locations (1)

Medical Research Labarotory, DoH, Aarhus University Hospital; 🇩🇰 Aarhus, Denmark