Nutritional Ketosis in Heart Failure (INNKA-HF)
Primary Purpose
Chronic Heart Failure
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
beta hydroxybutyrate (BHB) ester
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Heart Failure focused on measuring ketosis, beta-hydroxybutyrate, insulin, bioenergetics, exercise tolerance, metabolic, diabetes
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Group A
Group B
Arm Description
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).
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
Outcomes
Primary Outcome Measures
BHB Concentration in blood
Beta-hydroxybutyrate concentration in blood
Minutes at maximum exertion [Exercise Capacity]
Minutes at maximum exertion
Left ventricular ejection fraction (%)
Left ventricular ejection fraction, measured by echocardiogram
Cardiac output (L/min)
Cardiac output, measured by echocardiogram
Left ventricular end diastolic diameter (LVEDD) (cm)
LVEDD, measured by echocardiogram
Insulin concentration
Insulin concentration in blood
Bicarbonate concentration
Bicarbonate concentration in blood
Secondary Outcome Measures
Full Information
NCT ID
NCT04370600
First Posted
March 10, 2020
Last Updated
April 28, 2020
Sponsor
Thomas Jefferson University
1. Study Identification
Unique Protocol Identification Number
NCT04370600
Brief Title
Nutritional Ketosis in Heart Failure
Acronym
INNKA-HF
Official Title
A Phase 1, Crossover, Pharmacokinetic Study of Nutritional Ketosis on Exercise Capacity, Metabolic Adaptations, and Myocardial Function in Chronic Ambulatory Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
June 2020 (Anticipated)
Primary Completion Date
June 2021 (Anticipated)
Study Completion Date
June 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Thomas Jefferson University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Heart Failure
Keywords
ketosis, beta-hydroxybutyrate, insulin, bioenergetics, exercise tolerance, metabolic, diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Biological drug + placebo (Group A) or placebo + biological drug (Group B)
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
16 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Group B
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
beta hydroxybutyrate (BHB) ester
Other Intervention Name(s)
Delta G
Intervention Description
Ketone supplementation given 3x/day (60mL per dose, or 22g BHB)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Denatonium benzoate + HVMN ketone placebo flavor mix + Stevia
Primary Outcome Measure Information:
Title
BHB Concentration in blood
Description
Beta-hydroxybutyrate concentration in blood
Time Frame
1 Year
Title
Minutes at maximum exertion [Exercise Capacity]
Description
Minutes at maximum exertion
Time Frame
1 Year
Title
Left ventricular ejection fraction (%)
Description
Left ventricular ejection fraction, measured by echocardiogram
Time Frame
1 Year
Title
Cardiac output (L/min)
Description
Cardiac output, measured by echocardiogram
Time Frame
1 Year
Title
Left ventricular end diastolic diameter (LVEDD) (cm)
Description
LVEDD, measured by echocardiogram
Time Frame
1 Year
Title
Insulin concentration
Description
Insulin concentration in blood
Time Frame
1 Year
Title
Bicarbonate concentration
Description
Bicarbonate concentration in blood
Time Frame
1 Year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michael W Foster, M.D.
Phone
6107160962
Email
mfoster610@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Melissa McCarey
Phone
2155037417
Email
melissa.mccarey@jefferson.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J. Eduardo Rame, M.D.
Organizational Affiliation
Thomas Jefferson University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Nutritional Ketosis in Heart Failure
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