- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04370600
Nutritional Ketosis in Heart Failure (INNKA-HF)
A Phase 1, Crossover, Pharmacokinetic Study of Nutritional Ketosis on Exercise Capacity, Metabolic Adaptations, and Myocardial Function in Chronic Ambulatory Heart Failure
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Group A
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).
|
Ketone supplementation given 3x/day (60mL per dose, or 22g BHB)
Other Names:
Denatonium benzoate + HVMN ketone placebo flavor mix + Stevia
|
ACTIVE_COMPARATOR: Group B
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
|
Ketone supplementation given 3x/day (60mL per dose, or 22g BHB)
Other Names:
Denatonium benzoate + HVMN ketone placebo flavor mix + Stevia
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
BHB Concentration in blood
Time Frame: 1 Year
|
Beta-hydroxybutyrate concentration in blood
|
1 Year
|
Minutes at maximum exertion [Exercise Capacity]
Time Frame: 1 Year
|
Minutes at maximum exertion
|
1 Year
|
Left ventricular ejection fraction (%)
Time Frame: 1 Year
|
Left ventricular ejection fraction, measured by echocardiogram
|
1 Year
|
Cardiac output (L/min)
Time Frame: 1 Year
|
Cardiac output, measured by echocardiogram
|
1 Year
|
Left ventricular end diastolic diameter (LVEDD) (cm)
Time Frame: 1 Year
|
LVEDD, measured by echocardiogram
|
1 Year
|
Insulin concentration
Time Frame: 1 Year
|
Insulin concentration in blood
|
1 Year
|
Bicarbonate concentration
Time Frame: 1 Year
|
Bicarbonate concentration in blood
|
1 Year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: J. Eduardo Rame, M.D., Thomas Jefferson University
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- JT#15471
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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