Ketone Pharmacokinetic Study in HFrEF

NCT05757193 | Completed Phase 1 Results

• 2 other identifiers: Pro00111723K23HL161348
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test whether an over-the-counter ketone ester drink is well tolerated in people with heart failure on, and not on, a heart failure medication class called SGLT2 inhibitors. The research team is trying to determine the safest dose of Delta G. The study has a single visit. Participants will be served a light breakfast with the study drink, a physical exam will be conducted, and the study team will obtain information about demographics and medical history. The study team will draw blood intravenously up to eight times over the course of the half-day visit.

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

DeltaG; ketone ester; metabolites; metabolomics; ketoacidosis

Outcome Measures

Primary Outcomes (4)

• Venous pH Measured Via Peripheral Blood

  The pH scale ranges from 0 to 14, with 7 being neutral. Each number on the pH scale represents a ten-fold change in the acidity or basicity of a solution.

  1 hour

• Glucose Level Measured Via Peripheral Blood

  1 hour

• Systolic Blood Pressure

  Taken by blood pressure cuff on the arm

  1 hour

• Beta-hydroxybutyrate (BHB) Level Measured Via Peripheral Blood

  BHB is a chemical that is made by the body. It provides energy when not enough carbohydrates or sugars have been eaten.

  1 hour

Study Arms (2)

250 mg/kg ketone ester

EXPERIMENTAL

The first 5 patients within each SGLT2i stratum will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate at 250 mg/kg.

Dietary Supplement: DeltaG (250 mg/kg)

500 mg/kg ketone ester

EXPERIMENTAL

The second 5 patients within each SGLT2i stratum will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate at 500 mg/kg.

Dietary Supplement: DeltaG (500 mg/kg)

Interventions

DeltaG (250 mg/kg) DIETARY_SUPPLEMENT

250 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

250 mg/kg ketone ester

DeltaG (500 mg/kg) DIETARY_SUPPLEMENT

500 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

500 mg/kg ketone ester

Eligibility Criteria

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

You may qualify if:

• Diagnosis of HFrEF (ejection fraction\<=45%)
• Systolic blood pressure greater \>=90 mmHg

You may not qualify if:

• Intentional ketogenic (high fat, low carbohydrate) diet (must be off ketogenic diet for \>7 days prior to visit)
• Significant liver disease (cirrhosis) or alcohol abuse disorder (\>14 drinks/week).
• Unique cardiomyopathies: infiltrative/hypertrophic cardiomyopathy, pericardial disease, or other cardiomyopathies that in the investigator's opinion have unique treatment options that would be less likely to be affected by ketone therapy.
• Estimated glomerular filtration rate\<25 mL/min/1.73 m2 as the most recent value in the last year.
• Type 1 diabetes mellitus
• Use of ventricular assist device, history of heart transplant, or use of continuous inotropes

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• American Heart Association: collaborator

Study Sites (1)

Duke University

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Selvaraj S, Kwee LC, Thompson EJ, He M, Hornik CP, Devore AD, Patel CB, Mentz RJ, Fudim M, Taylor L, Milosovic S, Hurdle M, Cade WT, Ilkayeva O, Muehlbauer MJ, Newgard CB, Kelly DP, Zamani P, Margulies KB, Shah SH. Metabolic and Pharmacokinetic Profiling of a Ketone Ester by Background SGLT2 Inhibitor Therapy in HFrEF. JACC Basic Transl Sci. 2025 Mar;10(3):290-303. doi: 10.1016/j.jacbts.2024.10.014. Epub 2024 Nov 15.

  PMID: 40139871 DERIVED

MeSH Terms

Conditions

Ketosis

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Senthil Selvaraj, MD
• Organization: Duke University

Senthil.Selvaraj@duke.edu

919-660-0730

Study Officials

• Senthil Selvaraj, MD, MSTR, MA

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants stratified based on use of background use of SGLT2 inhibitors

Study Record Dates

• First Submitted: February 24, 2023
• First Posted: March 7, 2023
• Study Start: June 2, 2023
• Primary Completion: January 11, 2024
• Study Completion: January 11, 2024
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)