Functional and Metabolic Effects of Ketone Bodies on Human Atrial Tissue in Patients With and Without Heart Failure

Heart Failure Clinical Trial

Official title:

Functional and Metabolic Effects of Ketone Bodies on Human Atrial Tissue in Patients With and Without Heart Failure

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04379934
• Other study ID #: KetoCard01
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2020
• Est. completion date: January 31, 2024

Study information

• Verified date: April 2020
• Source: University of Aarhus
• Contact: Jacob Seefeldt, B.M
• Phone: +45 41178633
• Email: jacob.seefeldt[@]clin.au.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This proof of concept study aims to evaluate the effects of applying ketone bodies to human atrial tissue biopsies using an atrial strips model and high resolution respirometry.

Description:

Ketone bodies are high energy molecules which are naturally occurring in the body during fasting or stress.

Recently, ketone bodies have been shown to improve cardiac function in patients with heart failure(1) through a mechanism, which has yet to be elaborated.

We wish to evaluate the effects of ketone body administration on cardiac tissue subjected to ischemia reperfusion injury. We will evaluate contractile force of the and the mitochondrial performance. Cardiac atrial tissue will be obtained from patients undergoing coronary artery bypass grafting (CABG) or valve replacement surgery. Patients will be recruited after signing an informed consent and allocated in heart failure / non-heart failure groups based on a clinical evaluation.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• EF < / > 45%, hospitalized for elective CABG or heart valve surgery

Exclusion Criteria:

• Myocardial infarction within 4 weeks, atrial fibrillation, medically treated thyroid disease, oral treatment with opioids.

Related Conditions & MeSH terms

• Heart Failure
• Ischemia
• Ischemia Reperfusion Injury
• Mitochondrial Pathology
• Reperfusion Injury

Intervention

Dietary Supplement:
• 3-hydroxybuturate
3-hydroxybuturate will be administered directly as a modified Krebs Henseleit buffer in a super perfused atrial strips model

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

Nielsen R, Møller N, Gormsen LC, Tolbod LP, Hansson NH, Sorensen J, Harms HJ, Frøkiær J, Eiskjaer H, Jespersen NR, Mellemkjaer S, Lassen TR, Pryds K, Bøtker HE, Wiggers H. Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients. Circulation. 2019 Apr 30;139(18):2129-2141. doi: 10.1161/CIRCULATIONAHA.118.036459. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Contractile force recovery	Atrial strips model, contractile force (nm*mm^-1) during stabilization, ischemia and reperfusion	Outcome will be assessed within a year when the inclusion of patients is complete
Secondary	Mitochondrial respiratory capacity	High Resolution Respirometry, Complex I and Complex I+II respiration (pmol O2 · s-1·mg-1) assessed via a substrate and inhibitor (SUIT) protocol.	Outcome will be assessed within a year when the inclusion of patients is complete
Secondary	Mitochondrial Reactive Oxygen Species production	High Resolution FluoRespirometry, Complex I and Complex I+II linked ROS generation measured with AmplexUltra red and H2O2 interaction fluorescense	Outcome will be assessed within a year when the inclusion of patients is complete