Ignite Creation Date:
2025-12-24 @ 11:54 AM
Ignite Modification Date:
2025-12-26 @ 12:22 PM
Study NCT ID:
NCT04703361
Status:
COMPLETED
Last Update Posted:
2021-12-03
First Post:
2021-01-08
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effects of Ketones and Niacin in Heart Failure Patients
Sponsor:
University of Aarhus
Organization:
Study Overview
Official Title:
Effects of Ketones and Niacin in Heart Failure Patients
Status:
COMPLETED
Status Verified Date:
2020-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
KETO-COX
Brief Summary:
Ketones, 3-hydroxybutyrate (3-OHB), have shown to have beneficial hemodynamics effect in patients with hearth failure with reduced ejection fraction. The mechanisms behind these marked hemodynamic effects are currently unknown, but could involve prostaglandin-release. 3-OHB is the endogenous ligand for the G protein-coupled receptor hydroxy-carboxylic acid 2 (HCA2) receptor. This receptor has proven downstream effects on cAMP and systemic effects via release of prostaglandins.
In this present study we will investigate the cardiovascular effects of HCA2-receptor stimulation in heart failure patients.
In this present study we will investigate the cardiovascular effects of HCA2-receptor stimulation in heart failure patients.
Detailed Description:
Heart Failure (HF) is a major public health issue because the disease affects 1-2% of the Western population and the lifetime risk of HF is 20%. HF is responsible for 1-2% of all healthcare expenditures and 5% of all hospital admissions. The cornerstone in the medical treatment of chronic HF is a combination of ACE-inhibitors/ATII-receptor antagonists, beta-blockers and mineralocorticoid receptor antagonists. Despite major improvements in the management and care of patients with HF, the 1-year mortality in patients with HF is 13 % 4 and \>50% of HF-patients are admitted within a 2.5 year period 5. Furthermore, patients with HF have markedly decreased physical capacity and quality of life. Thus, there is a need for new treatment modalities in this group of patients.
Ketone bodies are produced in the liver and are crucial for energy generation during fasting in the heart and brain during, exercise and severe illnesses. However, ketosis can be safely obtained using dietary supplements and can increase exercise capacity in athletes. The most important ketone bodies are 3-hydroxybutyrate (3-OHB) and acetoacetate. Recently, it was demonstrated that patients with severe HF have increased myocardial utilization of the ketone body 3-OHB. It has been hypothesized that ketone bodies may act as a "superfuel" for the failing heart. In support of this, the glucose-lowering SGLT-2 inhibitor empagliflozin reduces the risk of hospitalizations and cardiovascular death in diabetic patients with HF and also increases circulating levels of 3-OHB.
By Positron Emission Tomography (PET) we have shown that ketone body infusion reduces myocardial glucose uptake and increases myocardial blood flow in healthy subjects. Data from another study conducted by our group show a 40% increase in cardiac output during infusion of 3-OHB. The mechanisms behind these marked hemodynamic effects are currently unknown, but could involve prostaglandin-release. 3-OHB is the endogenous ligand for the G protein-coupled receptor hydroxy-carboxylic acid 2 (HCA2) receptor. This receptor has proven downstream effects on cAMP and systemic effects via release of prostaglandins.
3-OHB have affinity to the HCA2 receptor and possibly a downstream effect resulting in the release of prostaglandins. The prostaglandin synthesis is dependent of cyclooxygenase (COX) enzyme, which can be inhibited by aspirin (ASA).
Niacin, vitamin B3, has been used as a treatment for dyslipidemia. Niacin is also a ligand for HCA2 receptor and the downstream release of prostaglandin cause side effects such as cutaneous flushing.
In this study we will investigate the cardiovascular effects of HCA2-receptor stimulation in heart failure patients. This will be done by comparing infusion of 3-OHB (preceded with ASA) and niacin.
Ketone bodies are produced in the liver and are crucial for energy generation during fasting in the heart and brain during, exercise and severe illnesses. However, ketosis can be safely obtained using dietary supplements and can increase exercise capacity in athletes. The most important ketone bodies are 3-hydroxybutyrate (3-OHB) and acetoacetate. Recently, it was demonstrated that patients with severe HF have increased myocardial utilization of the ketone body 3-OHB. It has been hypothesized that ketone bodies may act as a "superfuel" for the failing heart. In support of this, the glucose-lowering SGLT-2 inhibitor empagliflozin reduces the risk of hospitalizations and cardiovascular death in diabetic patients with HF and also increases circulating levels of 3-OHB.
By Positron Emission Tomography (PET) we have shown that ketone body infusion reduces myocardial glucose uptake and increases myocardial blood flow in healthy subjects. Data from another study conducted by our group show a 40% increase in cardiac output during infusion of 3-OHB. The mechanisms behind these marked hemodynamic effects are currently unknown, but could involve prostaglandin-release. 3-OHB is the endogenous ligand for the G protein-coupled receptor hydroxy-carboxylic acid 2 (HCA2) receptor. This receptor has proven downstream effects on cAMP and systemic effects via release of prostaglandins.
3-OHB have affinity to the HCA2 receptor and possibly a downstream effect resulting in the release of prostaglandins. The prostaglandin synthesis is dependent of cyclooxygenase (COX) enzyme, which can be inhibited by aspirin (ASA).
Niacin, vitamin B3, has been used as a treatment for dyslipidemia. Niacin is also a ligand for HCA2 receptor and the downstream release of prostaglandin cause side effects such as cutaneous flushing.
In this study we will investigate the cardiovascular effects of HCA2-receptor stimulation in heart failure patients. This will be done by comparing infusion of 3-OHB (preceded with ASA) and niacin.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: