NCT04703361

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2021

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 8, 2021

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 11, 2021

Completed
1 month until next milestone

Study Start

First participant enrolled

February 15, 2021

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 3, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 3, 2021

Completed
Last Updated

December 3, 2021

Status Verified

October 1, 2020

Enrollment Period

7 months

First QC Date

January 8, 2021

Last Update Submit

December 2, 2021

Conditions

Heart Failure, SystolicKetonemia

Outcome Measures

Primary Outcomes (1)

  • Cardiac Output

    L/min

    3 hours

Secondary Outcomes (4)

  • Mixed venous saturation

    3 hours

  • Pulmonary wedge pressure

    3 hours

  • Left ventricular ejection fraction

    3 hours

  • Circulating prostaglandin levels

    3 hours

Study Arms (2)

Niacin

EXPERIMENTAL

12 patients with Heart failure with reduced ejection fraction (HFrEF) investigated with echocardiography and right heart catheterization.

Biological: Placebo NaClBiological: Niacin

Na-3-OHB

EXPERIMENTAL

12 patients with Heart failure with reduced ejection fraction (HFrEF) investigated with echocardiography and right heart catheterization. All patients will receive Aspirin before intervention and randomization.

Biological: Placebo NaClBiological: Na-3-OHB

Interventions

Placebo NaClBIOLOGICAL

Placebo

Na-3-OHBNiacin
NiacinBIOLOGICAL

B3 vitamin, Niacin

Niacin
Na-3-OHBBIOLOGICAL

Na-3-OHB

Na-3-OHB

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Chronic heart failure, Age ≥ 18 years old, LVEF ≤40%, New York Heart Association (NYHA) classification 2-3, Negative urine-HCG for women of childbearing potential, Ability to understand the written patient information and to give informed consent.

You may not qualify if:

  • Symptomatic cardiac valve disease, Signs or history of major myocardial infarction (STEMI) within 1 month, Insulin treatment, Other disease or treatment making subject unsuitable for study participation as judged by the investigator.
  • Significant liver disease (defined by serum levels of alanine aminotransferase (ALAT) above 3 x upper limit of normal).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Related Publications (1)

  • Gopalasingam N, Christensen KH, Berg Hansen K, Nielsen R, Johannsen M, Gormsen LC, Boedtkjer E, Norregaard R, Moller N, Wiggers H. Stimulation of the Hydroxycarboxylic Acid Receptor 2 With the Ketone Body 3-Hydroxybutyrate and Niacin in Patients With Chronic Heart Failure: Hemodynamic and Metabolic Effects. J Am Heart Assoc. 2023 Jun 20;12(12):e029849. doi: 10.1161/JAHA.123.029849. Epub 2023 Jun 10.

    PMID: 37301762DERIVED

MeSH Terms

Conditions

Heart Failure, SystolicKetosis

Interventions

Niacin

Condition Hierarchy (Ancestors)

Heart FailureHeart DiseasesCardiovascular DiseasesAcidosisAcid-Base ImbalanceMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Nigopan Gopalasingam, MD

    University of Aarhus

    PRINCIPAL INVESTIGATOR

  • Henrik Wiggers, MD, PhD, DMSc

    Aarhus University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 8, 2021

First Posted

January 11, 2021

Study Start

February 15, 2021

Primary Completion

September 3, 2021

Study Completion

September 3, 2021

Last Updated

December 3, 2021

Record last verified: 2020-10

Data Sharing

IPD Sharing
Will not share

Locations

DK(1)