Chronic Heart FailurePhase 1INNKA-HFNCT04370600
Nutritional Ketosis in Heart Failure
A Phase 1 study testing beta hydroxybutyrate (BHB) ester in people with Chronic Heart Failure, run by Thomas Jefferson University.
Trial summary
Chronic, ambulatory heart failure patients will be given ketone ester dietary supplementation to determine therapeutic efficacy, metabolic adaptation, pharmacokinetics, associated cognitive changes, and safety within this patient cohort in order to establish preliminary data to later conduct a multi-center randomized… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Heart Failure
- What is being tested?
- beta hydroxybutyrate (BHB) ester
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- No sites listed yet
- Study dates
- Jun 2020to Jun 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Equal to or greater than 18 years of age
- Diagnosis of heart failure and be classified as NYHA Class II or III either pre-enrollment or at the time of enrollment
- Stable medical therapy for at least 1 month prior to enrollment
- Taking appropriate daily cardiac medications as determined by the principal investigator, who is a heart failure specialist
Who cannot join
- Atrial fibrillation
- Inability to exercise on a supine bicycle.
- Moderate or greater valvular disease.
- Hemoglobin <10 g/dL.
- Daily insulin use
- Hypertrophic, infiltrative, or inflammatory cardiomyopathy.
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- Pericardial disease.
- Current angina due to clinically significant obstructive epicardial coronary disease
- Acute coronary syndrome or coronary intervention within the past 2 months.
- Primary pulmonary arteriopathy.
- Known clinically significant lung disease defined as:
- Current use of supplemental oxygen, aside from nocturnal O2 for the treatment of obstructive sleep apnea
- The use of steroids/antibiotics within the past 6 months for an acute exacerbation of obstructive pulmonary disease
- Most proximal pulmonary function test indicating severe obstructive disease, defined as an FEV1<50% predicted in the context of an FEV1/FVC ratio of <0.70 ("Stage III COPD according to GOLD Criteria). (note: only to be used if the subject had PFTs prior to screening)
- Most proximal 6-minute walk test during which the subject experienced arterial desaturation (<94%) without a subsequent normal study.
- Ischemia on stress testing without subsequent revascularization or left heart catheterization showing non-obstructive epicardial coronary disease.
- Significant liver disease impacting synthetic function or volume control.
- Uncontrolled hypertension: BP >180/110 at baseline.
- eGFR <30 mL/min/m2 or Cr >2.5.
- Alcohol dependence
- Chronic narcotic use that cannot be interrupted
- Pregnant or lactating females
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Phase 1, Crossover, Pharmacokinetic Study of Nutritional Ketosis on Exercise Capacity, Metabolic Adaptations, and Myocardial Function in Chronic Ambulatory Heart Failure
Chronic, ambulatory heart failure patients will be given ketone ester dietary supplementation to determine therapeutic efficacy, metabolic adaptation, pharmacokinetics, associated cognitive changes, and safety within this patient cohort in order to establish preliminary data to later conduct a multi-center randomized clinical trial.
Read the detailed description
We previously demonstrated a metabolic signature of increased ketone utilization-increased peripheral blood concentration of beta-hydroxybutyrate (BHB) and decreased myocardial concentration of BHB-and markedly decreased acylcarnitine levels in the failing human myocardium procured from lean, non-diabetic patients with advanced heart failure at the time of cardiac transplantation. In this working model of the metabolic adaptations in human heart failure where the mobilization of lipids and ketones are required for an energetically deficient, failing heart it is likely that the development of insulin resistance may be adaptive since increased insulin or insulin signaling would put a brake on the hydrolysis of lipids and hepatic ketogenesis. In parallel with the recent discovery that the failing human heart is reliant on ketones, investigators at Oxford and the NIH have identified a nutritional ketone supplement that reliably increases the serum concentration of BHB in humans.
We hypothesize that the induction of ketosis by exogenous administration of the nutritional ketone monoester will improve myocardial function in heart failure by increasing the energetic substrate available to the myocardium, in essence supporting the energetic deficit of the failing human heart which we have demonstrated to be reliant on ketone bodies for fuel given the limited myocardial oxidation of glucose.
This is a prospective, double-blinded, sequence control crossover trial enrolling NYHA Class II-III ambulatory heart failure patients to receive either ketone mono-ester drink versus placebo for two weeks. Following 2 weeks of therapy, echocardiogram and peak exercise test will be performed. There will be a 1-week "washout" period between phases. Subjects will serve as their own controls for this crossover study, as each will have both baseline testing and testing in the setting of mild nutritional ketosis.
- Conditions
- Chronic Heart Failure
- Being tested
- beta hydroxybutyrate (BHB) ester, Placebo
- Keywords
- ketosis, beta-hydroxybutyrate, insulin, bioenergetics, exercise tolerance, metabolic, diabetes
- Medical subject headings
- Ketosis, Insulin Resistance, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
beta hydroxybutyrate (BHB) esterDrug
Also called Delta G
Ketone supplementation given 3x/day (60mL per dose, or 22g BHB)
PlaceboDrug
Denatonium benzoate + HVMN ketone placebo flavor mix + Stevia
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | These patients will receive ketone supplementation between visits 1 and 2 and will receive placebo drink between visits 2 and 3 (after the washout period). Receives: Drug: beta hydroxybutyrate (BHB) ester; Drug: Placebo |
| Group B | Active comparator | These patients will receive ketone supplementation between visits 2 and 3 (after the washout period) and will receive placebo drink between visits 1 and 2 Receives: Drug: beta hydroxybutyrate (BHB) ester; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
BHB Concentration in blood
Beta-hydroxybutyrate concentration in blood
Measured: 1 Year
Minutes at maximum exertion [Exercise Capacity]
Minutes at maximum exertion
Measured: 1 Year
Left ventricular ejection fraction (%)
Left ventricular ejection fraction, measured by echocardiogram
Measured: 1 Year
Cardiac output (L/min)
Cardiac output, measured by echocardiogram
Measured: 1 Year
Left ventricular end diastolic diameter (LVEDD) (cm)
LVEDD, measured by echocardiogram
Measured: 1 Year
Insulin concentration
Insulin concentration in blood
Measured: 1 Year
Bicarbonate concentration
Bicarbonate concentration in blood
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2020
- Study startJun 2020 (estimated)
- Primary completionJun 2021 (estimated)
- Study completionJun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Heart FailureStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Biological drug + placebo (Group A) or placebo + biological drug (Group B)
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- J. Eduardo Rame, M.D., Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04370600
- Sponsor's protocol ID
- JT#15471
- Acronym
- INNKA-HF
- Status last verified
- Apr 2020
- First submitted
- 10 Mar 2020
- Last updated
- 1 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Crossover, Pharmacokinetic Study of Nutritional Ketosis on Exercise Capacity, Metabolic Adaptations, and Myocardial Function in Chronic Ambulatory Heart Failure
- ClinicalTrials.gov ID
- NCT04370600
- Acronym / sponsor ID
- INNKA-HF / JT#15471
- Conditions
- Chronic Heart Failure
- Keywords
- ketosis, beta-hydroxybutyrate, insulin, bioenergetics, exercise tolerance, metabolic, diabetes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- Jun 2020 (estimated)
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 1 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic, ambulatory heart failure patients will be given ketone ester dietary supplementation to determine therapeutic efficacy, metabolic adaptation, pharmacokinetics, associated cognitive changes, and safety within this patient cohort in order to establish preliminary data to later conduct a multi-center randomized clinical trial.
Detailed description
We previously demonstrated a metabolic signature of increased ketone utilization-increased peripheral blood concentration of beta-hydroxybutyrate (BHB) and decreased myocardial concentration of BHB-and markedly decreased acylcarnitine levels in the failing human myocardium procured from lean, non-diabetic patients with advanced heart failure at the time of cardiac transplantation. In this working model of the metabolic adaptations in human heart failure where the mobilization of lipids and ketones are required for an energetically deficient, failing heart it is likely that the development of insulin resistance may be adaptive since increased insulin or insulin signaling would put a brake on the hydrolysis of lipids and hepatic ketogenesis. In parallel with the recent discovery that the failing human heart is reliant on ketones, investigators at Oxford and the NIH have identified a nutritional ketone supplement that reliably increases the serum concentration of BHB in humans.
We hypothesize that the induction of ketosis by exogenous administration of the nutritional ketone monoester will improve myocardial function in heart failure by increasing the energetic substrate available to the myocardium, in essence supporting the energetic deficit of the failing human heart which we have demonstrated to be reliant on ketone bodies for fuel given the limited myocardial oxidation of glucose.
This is a prospective, double-blinded, sequence control crossover trial enrolling NYHA Class II-III ambulatory heart failure patients to receive either ketone mono-ester drink versus placebo for two weeks. Following 2 weeks of therapy, echocardiogram and peak exercise test will be performed. There will be a 1-week "washout" period between phases. Subjects will serve as their own controls for this crossover study, as each will have both baseline testing and testing in the setting of mild nutritional ketosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Biological drug + placebo (Group A) or placebo + biological drug (Group B)
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Drug: beta hydroxybutyrate (BHB) ester, Drug: PlaceboThese patients will receive ketone supplementation between visits 1 and 2 and will receive placebo drink between visits 2 and 3 (after the washout period). |
| Group B | Active comparator | Drug: beta hydroxybutyrate (BHB) ester, Drug: PlaceboThese patients will receive ketone supplementation between visits 2 and 3 (after the washout period) and will receive placebo drink between visits 1 and 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Equal to or greater than 18 years of age
- Diagnosis of heart failure and be classified as NYHA Class II or III either pre-enrollment or at the time of enrollment
- Stable medical therapy for at least 1 month prior to enrollment
- Taking appropriate daily cardiac medications as determined by the principal investigator, who is a heart failure specialist
Key exclusion criteria (22 listed)
- Atrial fibrillation
- Inability to exercise on a supine bicycle.
- Moderate or greater valvular disease.
- Hemoglobin <10 g/dL.
- Daily insulin use
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 |
|---|---|---|
| beta hydroxybutyrate (BHB) esterAlso: Delta GKetone supplementation given 3x/day (60mL per dose, or 22g BHB) | Drug | Group A, Group B |
| PlaceboDenatonium benzoate + HVMN ketone placebo flavor mix + Stevia | Drug | Group A, Group B |
Primary outcome
BHB Concentration in blood
Time frame: 1 Year
Beta-hydroxybutyrate concentration in blood
Minutes at maximum exertion [Exercise Capacity]
Time frame: 1 Year
Minutes at maximum exertion
Left ventricular ejection fraction (%)
Time frame: 1 Year
Left ventricular ejection fraction, measured by echocardiogram
Cardiac output (L/min)
Time frame: 1 Year
Cardiac output, measured by echocardiogram
Left ventricular end diastolic diameter (LVEDD) (cm)
Time frame: 1 Year
LVEDD, measured by echocardiogram
Insulin concentration
Time frame: 1 Year
Insulin concentration in blood
Bicarbonate concentration
Time frame: 1 Year
Bicarbonate concentration in blood
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2020.
- 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.
J. Eduardo Rame, M.D. principal investigator
Thomas Jefferson University
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing beta hydroxybutyrate (BHB) ester in people with Chronic Heart Failure, run by Thomas Jefferson University.
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 4 inclusion and 22 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: status not confirmed, as of the sponsor's last update on 1 May 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael W Foster, M.D. (6107160962, mfoster610@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BHB Concentration in blood (time frame: 1 Year). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 May 2020; AzTrials last refreshed its copy on 31 Oct 2026.