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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Ischemia Reperfusion Injury; Mitochondrial Pathology
• Intervention / Treatment: Dietary supplement: 3-hydroxybuturate

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jacob Seefeldt, B.M; Phone Number: +45 41178633; Email: jacob.seefeldt@clin.au.dk
• Study Contact Backup: Name: Bent Roni Nielsen, M.D., PhD.; Phone Number: +45 51 21 93 63‬; Email: bent.nils@midt.rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
    • Contact: Jacob Seefeldt, M.B.; Phone Number: +45 4117633; Email: jacob.seefeldt@clin.au.dk
    • Contact: Bent Roni Nielsen, M.D., Ph.D.; Phone Number: +45 51219363; Email: bent.nils@midt.rm.dk
    • Principal Investigator: Bent Roni Nielsen, M.D., PhD
    • Sub-Investigator: Jacob Seefeldt, M.B

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Heart failure; Ejection fraction < 45%	Dietary supplement: 3-hydroxybuturate; 3-hydroxybuturate will be administered directly as a modified Krebs Henseleit buffer in a super perfused atrial strips model
Other: Non-heart failure; Ejection fraction > 45%	Dietary supplement: 3-hydroxybuturate; 3-hydroxybuturate will be administered directly as a modified Krebs Henseleit buffer in a super perfused atrial strips model

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Study Director: Hans Erik Bøtker, M.D., Prof., Aarhus University Hospital

Publications and helpful links

General Publications

• Nielsen R, Moller N, Gormsen LC, Tolbod LP, Hansson NH, Sorensen J, Harms HJ, Frokiaer J, Eiskjaer H, Jespersen NR, Mellemkjaer S, Lassen TR, Pryds K, Botker 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): January 31, 2024
• Study Completion (Anticipated): January 31, 2024

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 8, 2020

Study Record Updates

• Last Update Posted (Actual): May 8, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Heart Failure; Ischemia; Reperfusion Injury
• Other Study ID Numbers: KetoCard01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No