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NCT03560323: Protocol1

Ketones, Muscle Metabolism, and SGLT2 Inhibitors - Protocol 1

Completed Phase 1 Results posted Last updated 29 September 2025
What this trial tests

Phase 1 trial testing Beta-hydroxy-butyrate in Heart Failure in 41 participants. Completed in 30 December 2024.

Timeline
7 January 2019
Primary endpoint
30 August 2024
30 December 2024

Quick facts

Lead sponsorThe University of Texas Health Science Center at San Antonio
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposebasic science
Enrollment41
Start date7 January 2019
Primary completion30 August 2024
Estimated completion30 December 2024
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

The University of Texas Health Science Center at San Antonio

Who can join

Adults 18 to 80, any sex, with Heart Failure or Type 2 Diabetes Mellitus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cardiac Output (CO) Primary · Baseline at 0 minute before B-OH-B infusion and 360 minutes after B-OH-B infusion for Group I & II. For Group III was baseline at 0 minute and 180 minutes after infusion

Within 2 weeks after the screening visit, subjects return to the Research Institute (RII) at 7:00AM for a cardiac MRI on 3.0T MRI System (TIM, Trio, Siemens Medical Solution, Malvern, PA). Cardiac output (CO) is measured using velocity encoded phase contrast MRI. The patient lies in the MRI scanner, and the imaging plane is positioned perpendicular to the ascending aorta where blood flow can be measured accurately. The MRI scan is synchronized with the patient's heartbeats using ECG gating. Two types of images are collected: magnitude images, which provide anatomical reference, phase images,

Baseline:before Beta-H-B infusion infusion
GroupValue95% CI
Group I Beta-Hydroxy-Butyrate5.02± 0.38
Group II Beta-Hydroxy-Butyrate4.54± 0.28
Group III Beta-Hydroxy-Butyrate5.93± 0.36
After Beta-H-B infusion infusion
GroupValue95% CI
Group I Beta-Hydroxy-Butyrate5.10± 0.41
Group II Beta-Hydroxy-Butyrate5.3± 0.22
Group III Beta-Hydroxy-Butyrate7.16± 0.44
Ejection Fraction (EF) Primary · Baseline at 0 minute before infusion and 360 minutes after infusion for Group I & II. Group III was baseline at 0 minute of infusion and 180 minutes after infusion

A measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each heartbeat. It's a key indicator of heart function and can help diagnose and track heart failure. A normal EF typically falls between 55% and 70%. Values below 40% are often considered indicative of heart failure.

GroupValue95% CI
Group I Beta-Hydroxy-Butyrate0.1± 1.2
Group II Beta-Hydroxy-Butyrate3.9± 3.5
Group III Beta-Hydroxy-Butyrate6.4± 4.5
Left Ventricular Stroke Volume (LVSV) Primary · Baseline at 0 minute before infusion and 360 minutes after infusion for Group I & II. Group III was baseline at 0 minute of infusion and 180 minutes after infusion

Represents the amount of blood ejected from the heart's left ventricle with each heartbeat. It's a crucial indicator of cardiac function, reflecting how effectively the heart pumps blood to the body.

GroupValue95% CI
Group I Beta-Hydroxy-Butyrate0.3± 1.3
Group II Beta-Hydroxy-Butyrate9.7± 6.4
Group III Beta-Hydroxy-Butyrate19.4± 6.0
Myocardial Energetics-Myocardial Glucose Uptake (MGU) Secondary · MGU after B-OH-B or NaHCO3 infusion for 6 hours at minute 360 minutes

A sub-set of participants in group II also underwent a cardiac PET study to examine the effect of hyperketonemia on Myocardial Glucose Uptake (MGU) and Myocardial Blood Flow MBF). A 20-min transmission scan was performed after exposure to a retractable 68Ge ring source to correct emission data for tissue attenuation of g photons. Then, 15O-H2O (10.5 MBq/kg) was administered intravenously through the antecubital vein catheter over 20 s, and a PET scan was performed to measure MBF. Participants underwent a 6-h b-OH-B infusion (prime dose was 1.5 mg/kg/min for 20 min followed by constant rate of

Beta -H-B infusion
GroupValue95% CI
Group II Beta-Hydroxy-Butyrate9.6± 1.01
NaHCO3 infusion
GroupValue95% CI
Group II Beta-Hydroxy-Butyrate8.56± 0.74
Myocardial Energetics- Myocardic Blood Flow (MBF) Secondary · MBF after B-OH-B or NaHCO3 infusion for 6 hours at 360 minutes (the results showed the difference betweenB-OH-B and NaHCO3 infusion for 6 hours)

A sub-set of participants in group II also underwent a cardiac PET study to examine the effect of hyperketonemia on Myocardial Glucose Uptake (MGU) and Myocardial Blood Flow MBF). A 20-min transmission scan was performed after exposure to a retractable 68Ge ring source to correct emission data for tissue attenuation of g photons. Then, 15O-H2O (10.5 MBq/kg) was administered intravenously through the antecubital vein catheter over 20 s, and a PET scan was performed to measure MBF. Participants underwent a 6-h b-OH-B infusion (prime dose was 1.5 mg/kg/min for 20 min followed by constant rate of

GroupValue95% CI
Group II Beta-Hydroxy-Butyrate0.05± 0.10

Sponsor's own description

To examine the effect of an increase in plasma beta-hydroxy-butyrate (B-OH-B) levels, spanning the physiologic and pharmacologic range (+0.5, +2.0, and +5.0 mmol/L), on: (i) parameters of left ventricular (LV) systolic and diastolic function utilizing cardiac magnetic resonance imaging (MRI) and (ii) myocardial glucose uptake using positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose in type 2 diabetic patients with Class II-III New York Heart Association (NYHA).

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Ketones and the Heart: Metabolic Principles and Therapeutic Implications.
    Matsuura TR, Puchalska P, Crawford PA, Kelly DP. · · 2023 · cited 123× · PMID 36996176 · DOI 10.1161/circresaha.123.321872
  2. The therapeutic potential of ketones in cardiometabolic disease: impact on heart and skeletal muscle.
    Soni S, Tabatabaei Dakhili SA, Ussher JR, Dyck JRB. · · 2024 · cited 18× · PMID 38193855 · DOI 10.1152/ajpcell.00501.2023
  3. Effect of Hyperketonemia on Myocardial Function in Patients With Heart Failure and Type 2 Diabetes.
    Solis-Herrera C, Qin Y, Honka H, Cersosimo E, et al · · 2025 · cited 5× · PMID 39446133 · DOI 10.2337/db24-0406
  4. Ketones in Cardiovascular Health and Disease: An Updated Review.
    Shrestha S, Harrison I, Dosunmu A, Song P. · · 2026 · PMID 41597225 · DOI 10.3390/cells15020150

Verify or expand the search:

Other recruiting trials for Heart Failure

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Data sources for this page

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing