Hemodynamic Effects of Modulating Circulating Ketone Bodies With 1,3-butanediol

NCT05768100 | Completed Phase 2 DMC

• 1 other identifier: 1-10-72-8-23
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Heart Failure (HF) is a major public health issue affecting 1-2% of the Western population and the lifetime risk of HF is 20%. Despite major improvements in the management and care of patients with HF, the 1-year mortality in patients with HF is high. 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. In a first-in-man study we have recently discovered that 3-OHB-infusion increases cardiac output by 2 L/min (40% relative increase) and left ventricular (LV) ejection fraction (LVEF) by 8% in absolute numbers in patients with HF and reduced LVEF (HFrEF). 1,3-Butanediol (BD) serves as a potential nutritional supplement in providing long-lasting ketosis as a treatment option in heart disease. Whether BD provides similar hemodynamic effects as ketone monoester remains unknown. Hypothesis Oral BD increases cardiac output and LV function in patients with HFrEF. Aims To investigate the acute hemodynamic effects of weight-adjusted oral BD supplements in patients with HFrEF. Design In a randomized, single-blind, placebo-controlled, crossover design, 12 patients with HFrEF are studied following overnight fast on 2 separate visits in random order: 1) during intake of BD (HVMN, San Francisco, California, USA) and during placebo. Methods Transthoracic echocardiography, non-invasive blood pressure, and venous blood samples are obtained every 60 minutes from baseline until 6 hours following BD ingestion.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Cardiac output

  As measured by LVOT VTI and HR

  6 hours

Secondary Outcomes (5)

• Stroke volume

  6 hours

• Heart rate

  6 hours

• LVEF

  6 hours

• Changes in circulating 3-OHB

  6 hours

• Changes in FFA

  6 hours

Study Arms (2)

1,3-Butanediol

EXPERIMENTAL

Dietary Supplement: 1,3-Butanediol

Placebo

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

1,3-Butanediol DIETARY_SUPPLEMENT

1,3-Butanediol

Also known as: Ketone-IQ (HVMN)

1,3-Butanediol

Placebo DIETARY_SUPPLEMENT

Isovolumic placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic HF: NYHA class II-III, LVEF \<40%. Negative urine-HCG for women with childbearing potential. Age ≥18 years.

You may not qualify if:

• Diabetes or HbA1c \>48 mmol/mol, significant cardiac valve disease, severe stable angina pectoris, severe comorbidity as judged by the investigator, inability to give informed consent.

Sponsors & Collaborators

• Aarhus University Hospital: lead

Study Sites (1)

Dept. of Cardiology, Aarhus University Hospital

Aarhus, Denmark

Location

Related Publications (1)

• Guldbrandsen H, Gopalasingam N, Christensen KH, Horsdal OK, Nielsen R, Wiggers H, Berg-Hansen K. Cardiovascular and Metabolic Effects of Modulating Circulating Ketone Bodies With 1,3-Butanediol in Patients With Heart Failure With Reduced Ejection Fraction. J Am Heart Assoc. 2025 Jan 7;14(1):e038461. doi: 10.1161/JAHA.124.038461. Epub 2024 Dec 24.

  PMID: 39719429 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

1,3-butylene glycol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

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: March 2, 2023
• First Posted: March 14, 2023
• Study Start: April 1, 2023
• Primary Completion: September 1, 2023
• Study Completion: March 1, 2024
• Last Updated: March 22, 2024

Record last verified: 2023-03

Locations

DK (1)