Heart Failure With Reduced Ejection FractionPhase 1NCT05757193
Ketone Pharmacokinetic Study in HFrEF
A Phase 1 study testing DeltaG (250 mg/kg) and DeltaG (500 mg/kg) in people with Heart Failure With Reduced Ejection Fraction, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction
- What is being tested?
- DeltaG (250 mg/kg) and DeltaG (500 mg/kg)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 2023to 11 Jan 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of HFrEF (ejection fraction<=45%)
- Systolic blood pressure greater >=90 mmHg
Who cannot join
- 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
- Pregnant women. Due to unknown affects of nutritional ketosis in pregnant women, pregnancy will be an exclusion. Accordingly, women of childbearing age with a menstrual cycle within the past year will be asked to submit a urine specimen for pregnancy testing.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ketone Pharmacokinetic Study in Heart Failure With Reduced Ejection Fraction
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.
- Being tested
- DeltaG (250 mg/kg), DeltaG (500 mg/kg)
- Keywords
- DeltaG, ketone ester, metabolites, metabolomics, ketoacidosis
- Medical subject headings
- Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DeltaG (250 mg/kg)Dietary supplement
250 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate
DeltaG (500 mg/kg)Dietary supplement
500 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Dietary Supplement: DeltaG (500 mg/kg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 hour
Glucose Level Measured Via Peripheral Blood
Measured: 1 hour
Systolic Blood Pressure
Taken by blood pressure cuff on the arm
Measured: 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.
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2023
- Study start2 Jun 2023
- Primary completion11 Jan 2024
- Study completion11 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Participants stratified based on use of background use of SGLT2 inhibitors
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), American Heart Association
- Responsible party
- Sponsor
- Investigators
- Senthil Selvaraj, MD, MSTR, MA, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05757193
- Sponsor's protocol ID
- Pro00111723
- Other IDs
- K23HL161348
- Status last verified
- Dec 2024
- First submitted
- 24 Feb 2023
- Last updated
- 27 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40139871
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketone Pharmacokinetic Study in Heart Failure With Reduced Ejection Fraction
- ClinicalTrials.gov ID
- NCT05757193
- Acronym / sponsor ID
- Pro00111723
- Keywords
- DeltaG, ketone ester, metabolites, metabolomics, ketoacidosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), American Heart Association
- Study start
- 2 Jun 2023 (actual)
- Primary completion
- 11 Jan 2024 (actual)
- Study completion
- 11 Jan 2024 (actual)
- First posted
- 7 Mar 2023 (actual)
- Results
- Posted 27 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants stratified based on use of background use of SGLT2 inhibitors
| Arm | Type | Receives |
|---|---|---|
| 250 mg/kg ketone ester | Experimental | Dietary Supplement: DeltaG (250 mg/kg)The first 5 patients within each SGLT2i stratum will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate at 250 mg/kg. |
| 500 mg/kg ketone ester | Experimental | Dietary Supplement: DeltaG (500 mg/kg)The second 5 patients within each SGLT2i stratum will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate at 500 mg/kg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnosis of HFrEF (ejection fraction<=45%)
- Systolic blood pressure greater >=90 mmHg
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DeltaG (250 mg/kg)250 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate | Dietary supplement | 250 mg/kg ketone ester |
| DeltaG (500 mg/kg)500 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate | Dietary supplement | 500 mg/kg ketone ester |
Primary outcome
Venous pH Measured Via Peripheral Blood
Time frame: 1 hour
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.
Glucose Level Measured Via Peripheral Blood
Time frame: 1 hour
Systolic Blood Pressure
Time frame: 1 hour
Taken by blood pressure cuff on the arm
Beta-hydroxybutyrate (BHB) Level Measured Via Peripheral Blood
Time frame: 1 hour
BHB is a chemical that is made by the body. It provides energy when not enough carbohydrates or sugars have been eaten.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40139871Selvaraj 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Senthil Selvaraj, MD, MSTR, MA principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DeltaG (250 mg/kg) and DeltaG (500 mg/kg) in people with Heart Failure With Reduced Ejection Fraction, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Venous pH Measured Via Peripheral Blood (time frame: 1 hour). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05757193, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2024.