NCT02814474

Brief Summary

Starvation and metabolic stress increase circulating ketone bodies, potentially providing the heart with an alternative oxidative fuel. Hyperketonemia reduces myocardial fatty acid consumption. It is unclear whether this is due to inhibited peripheral lipolysis or diminished uptake per se. Aim: To test whether infusion of 3-hydroxybutyrate (BHB) inhibits myocardial glucose and fatty acid uptake. Methods: Randomized, single blinded, cross-over interventional study in 8 healthy volunteers. Myocardial glucose and fatty acid metabolism studied by 11C-palmitate and 18F-FDG PET/CT. Experimental elevation of circulating ketone bodies by infusion of β-hydroxy-β-methylbutyrate.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
10

participants targeted

Target at P25-P50 for early_phase_1 healthy-volunteers

Timeline
Completed

Started Oct 2014

Typical duration for early_phase_1 healthy-volunteers

Geographic Reach
1 country

2 active sites

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

Study Start

First participant enrolled

October 1, 2014

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
22 days until next milestone

First Submitted

Initial submission to the registry

June 23, 2016

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 27, 2016

Completed
Last Updated

July 4, 2016

Status Verified

June 1, 2016

Enrollment Period

1.7 years

First QC Date

June 23, 2016

Last Update Submit

July 1, 2016

Conditions

Healthy Volunteers

Keywords

PET/CTHeart failurehydroxybutyrate

Outcome Measures

Primary Outcomes (3)

  • Myocardial Glucose uptake

    Dynamic 18F-FDG PET/CT scan - 50 minutes

    After 330 minutes of ketone infusion

  • Myocardial Fatty Acid Metabolism

    Dynamic 11C-palmitate PET/CT scan - 50 minutes

    After 210 minutes of ketone infusion

  • Myocardial Blood Flow

    Dynamic 15O-H2O PET/CT scan - 6 minutes

    After 180 minutes of ketone infusion

Secondary Outcomes (1)

  • Insulin sensitivity

    Time 0-390 of the ketone body infusion

Study Arms (2)

SALINE

PLACEBO COMPARATOR

Infusion of saline (0.9 %)

Other: Saline

KETONE

EXPERIMENTAL

Infusion of Na-3-Hydroxybutyrate (0.18 g/kg/hour) for 390 minutes

Other: Na-3-hydroxybutyrate

Interventions

Na-3-hydroxybutyrateOTHER

Infusion of Na-3-hydroxybutyrate (0.18 g/kg/hour) for 390 minutes

KETONE
SalineOTHER

Infusion of 0.9 % saline

SALINE

Eligibility Criteria

Age50 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy volunteers

You may not qualify if:

  • Decreased cardiac function
  • Kidney disease
  • Pulmonary disease
  • Current malignant disease
  • Substance abuse
  • Blood donation within 6 month prior to the study
  • Participation in studies involving ionising radiation within 12 month prior to the study
  • Known claustrophobia

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Department of Nuclear Medicine & PET Center, Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Medical Research Laboratories

Aarhus, 8000, Denmark

Location

Related Publications (3)

  • Svart M, Gormsen LC, Espersen R, Rittig N, Starup-Linde J, Moller N, Rejnmark L. 3-Hydroxybutyrate administration elevates plasma parathyroid hormone in a pilot human randomized, controlled, cross over trial. Bone. 2021 Dec;153:116166. doi: 10.1016/j.bone.2021.116166. Epub 2021 Aug 28.

    PMID: 34464780DERIVED

  • Lauritsen KM, Sondergaard E, Luong TV, Moller N, Gormsen LC. Acute Hyperketonemia Does Not Affect Glucose or Palmitate Uptake in Abdominal Organs or Skeletal Muscle. J Clin Endocrinol Metab. 2020 Jun 1;105(6):dgaa122. doi: 10.1210/clinem/dgaa122.

    PMID: 32161953DERIVED

  • Lauritsen KM, Sondergaard E, Svart M, Moller N, Gormsen LC. Ketone Body Infusion Increases Circulating Erythropoietin and Bone Marrow Glucose Uptake. Diabetes Care. 2018 Dec;41(12):e152-e154. doi: 10.2337/dc18-1421. Epub 2018 Oct 16. No abstract available.

    PMID: 30327354DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

ChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Niels Møller, MD DMsc

    Aarhus University Hospital

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 23, 2016

First Posted

June 27, 2016

Study Start

October 1, 2014

Primary Completion

June 1, 2016

Study Completion

June 1, 2016

Last Updated

July 4, 2016

Record last verified: 2016-06

Locations

DK(2)