Back to resultsFunctional and Metabolic Effects of Ketone Bodies on Human Atrial Tissue in Patients With and Without Heart Failure
Primary Purpose
Heart Failure, Ischemia Reperfusion Injury, Mitochondrial Pathology
Status
Not yet recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
3-hydroxybuturate
Sponsored by
About this trial
This is an interventional basic science trial for Heart Failure
Eligibility Criteria
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.
Sites / Locations
- Aarhus University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
Heart failure
Non-heart failure
Arm Description
Ejection fraction < 45%
Ejection fraction > 45%
Outcomes
Primary Outcome Measures
Contractile force recovery
Atrial strips model, contractile force (nm*mm^-1) during stabilization, ischemia and reperfusion
Secondary Outcome Measures
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.
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
Full Information
NCT ID
NCT04379934
First Posted
April 30, 2020
Last Updated
May 4, 2020
Sponsor
University of Aarhus
Collaborators
Aarhus University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04379934
Brief Title
Functional and Metabolic Effects of Ketone Bodies on Human Atrial Tissue in Patients With and Without Heart Failure
Official Title
Functional and Metabolic Effects of Ketone Bodies on Human Atrial Tissue in Patients With and Without Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 1, 2020 (Anticipated)
Primary Completion Date
January 31, 2024 (Anticipated)
Study Completion Date
January 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus
Collaborators
Aarhus University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Ischemia Reperfusion Injury, Mitochondrial Pathology
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Heart failure
Arm Type
Other
Arm Description
Ejection fraction < 45%
Arm Title
Non-heart failure
Arm Type
Other
Arm Description
Ejection fraction > 45%
Intervention Type
Dietary Supplement
Intervention Name(s)
3-hydroxybuturate
Intervention Description
3-hydroxybuturate will be administered directly as a modified Krebs Henseleit buffer in a super perfused atrial strips model
Primary Outcome Measure Information:
Title
Contractile force recovery
Description
Atrial strips model, contractile force (nm*mm^-1) during stabilization, ischemia and reperfusion
Time Frame
Outcome will be assessed within a year when the inclusion of patients is complete
Secondary Outcome Measure Information:
Title
Mitochondrial respiratory capacity
Description
High Resolution Respirometry, Complex I and Complex I+II respiration (pmol O2 · s-1·mg-1) assessed via a substrate and inhibitor (SUIT) protocol.
Time Frame
Outcome will be assessed within a year when the inclusion of patients is complete
Title
Mitochondrial Reactive Oxygen Species production
Description
High Resolution FluoRespirometry, Complex I and Complex I+II linked ROS generation measured with AmplexUltra red and H2O2 interaction fluorescense
Time Frame
Outcome will be assessed within a year when the inclusion of patients is complete
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jacob Seefeldt, B.M
Phone
+45 41178633
Email
jacob.seefeldt@clin.au.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Bent Roni Nielsen, M.D., PhD.
Phone
+45 51 21 93 63
Email
bent.nils@midt.rm.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans Erik Bøtker, M.D., Prof.
Organizational Affiliation
Aarhus University Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacob Seefeldt, M.B.
Phone
+45 4117633
Email
jacob.seefeldt@clin.au.dk
First Name & Middle Initial & Last Name & Degree
Bent Roni Nielsen, M.D., Ph.D.
Phone
+45 51219363
Email
bent.nils@midt.rm.dk
First Name & Middle Initial & Last Name & Degree
Bent Roni Nielsen, M.D., PhD
First Name & Middle Initial & Last Name & Degree
Jacob Seefeldt, M.B
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30884964
Citation
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.
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Functional and Metabolic Effects of Ketone Bodies on Human Atrial Tissue in Patients With and Without Heart Failure
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