Reverse HFpEF: Ketogenic Reversal of Heart Failure With Preserved Ejection Fraction Study
Study Details
Study Description
Brief Summary
This protocol is a prospective pilot study utilizing the intervention of a medically supervised, registered nurse and registered diabetes educator coached low-carbohydrate, ketogenic diet to examine the impact it has as a treatment for heart failure with preserved ejection fraction.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HFpEF Patients diagnosed with obesity related heart failure with preserved ejection fraction(HFpEF) |
Other: Ketogenic Diet
Ketogenic diet intervention that is high in fat and low in carbohydrates, causing the body to induce a state of metabolic ketosis, whereby fat is broken down into ketones to provide an energy source for the body.
|
| Experimental: PH-HFpEF Patients diagnosed with obesity related pulmonary hypertension heart failure with preserved ejection fraction (PH-HFpEF) |
Other: Ketogenic Diet
Ketogenic diet intervention that is high in fat and low in carbohydrates, causing the body to induce a state of metabolic ketosis, whereby fat is broken down into ketones to provide an energy source for the body.
|
Outcome Measures
Primary Outcome Measures
- MLHFQ Questionnaire [6 Months]
Change in score on the Minnesota Living with Heart Failure Quality of Life (MLHFQ) Questionnaire for the HFpEF cohort. Max. Score = 105 Min. Score = 0 A reduced score means improvement of heart failure symptoms; better outcome
- PAH-SYMPACT Questionnaire [6 Months]
Change in score on the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire for the PH-HFpEF cohort. Max. Score = 89 Min. Score = 0 A reduced score means improvement of pulmonary hypertension heart failure symptoms; better outcome
Secondary Outcome Measures
- Change in Metabolic Health: Weight [6 Months]
Weight in kilograms (kg)
- Change in Metabolic Health: Glucose [6 Months]
Glucose in milligrams per deciliter (mg/dL)
- Change in Metabolic Health: Insulin [6 Months]
Insulin in microinternational unit per milliliter (uIU/mL)
- Change in Metabolic Health: Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [6 Months]
Insulin and glucose are multiplied then divided by 405 to report HOMA-IR
- Change in Metabolic Health: Albumin [6 Months]
Albumin in grams per deciliter (g/dL)
- Change in Metabolic Health: Bilirubin total [6 Months]
Bilirubin total in milligrams per deciliter (mg/dL)
- Change in Metabolic Health: Alanine Transaminase (ALT) [6 Months]
ALT in units per liter (U/L)
- Change in Metabolic Health: Aspartate Aminotransferase (AST) [6 Months]
AST in units per liter (U/L)
- Change in Metabolic Health: Alkaline Phosphatase (ALP) [6 Months]
ALP in units per liter (U/L)
- Change in Metabolic Health: High Sensitivity C-Reactive Protein (HS-CRP) [6 Months]
HS-CRP in milligrams per deciliter (mg/dL)
- Change in Metabolic Health: Triglycerides [6 Months]
triglyceride in milligrams per deciliter (mg/dL)
- Change in Metabolic Health: High Density Lipoprotein (HDL) [6 Months]
HDL in milligrams per deciliter (mg/dL)
- Change in Metabolic Health: Hemoglobin A1c [6 Months]
hemoglobin A1c in percent (%)
- Change in Metabolic Health: Body Mass Index (BMI) [6 Months]
Weight and height will be combined to report BMI in kg/m^2
- Changes in Physical Function: 6 Minute Walk Test (6MWT) [6 Months]
6-minute walk test is reported in meters (m) of how far a subject walks in 6 minutes
- Changes in Physical Function: Maximum Oxygen Consumption (VO2max) [6 Months]
VO2 max is reported in liters per minute (L/min) while performing a cardiopulmonary exercise test (CPET)
- Changes in Physical Function: Maximum Work [6 Months]
Maximum work achieved while performing a cardiopulmonary exercise test (CPET) is reported in watts (W)
- Changes in Physical Function: 30 Second Sit-to-Stand test (30s STS) [6 Months]
30s STS is reported in quantity of how many times the subject can come to a full stand from a seated position in 30 seconds (s)
- Changes in Physical Function: Leg Press - 1 Repetition Maximum [6 Months]
Leg press is reported in kilograms (kg)
- Changes in Physical Function: Chest Press - 1 Repetition Maximum [6 Months]
Chest press is reported in kilograms (kg)
- Changes in Physical Function: Leg Extension - 1 Repetition Maximum [6 Months]
Leg extension is reported in kilograms (kg)
- Cardiac Remodeling: Changes in the Left Ventricle (LV) size [6 Months]
This is determined by the internal diameter measurement of the LV, reported in centimeters (cm) from a subject performed echocardiogram
- Cardiac Remodeling: Changes in the Left Ventricle (LV) thickness [6 Months]
This is determined by a measurement of the LV wall, reported in millimeters (mm) from an echocardiogram.
- Cardiac Remodeling: Changes in the Left Ventricle (LV) mass [6 Months]
This is determined by a combination formula of the interventricular septum diastole (IVSd), left ventricle diastole (LVd), and posterior wall diastole (PWd), calculated by an echocardiogram and reported in grams (g).
- Cardiac Remodeling: Changes in Left Atrium (LA) size [6 Months]
This is determined by the internal diameter measurement of the LA, reported in centimeters (cm) from a subject performed echocardiogram.
- Cardiac Remodeling: Changes in Inferior Vena Cava (IVC) size [6 Months]
This is determined by the internal diameter perpendicular to the long axis of the IVC at the end-expiration, reported in centimeters (cm) from the echocardiogram.
- Cardiac Remodeling: Changes in estimated Right Atrial Pressure (RAP) [6 Months]
This is determined by a combination equation subtracting the venous return (VR) from the central venous pressure (CVP), reported in millimeters of mercury (mmHg) from the echocardiogram.
- Cardiac Remodeling: Changes in Right Ventricle Systolic Pressure (RVSP) [6 Months]
This estimates the pressure inside the artery that supplies the lung with blood, reported in millimeters of mercury (mmHg) from the echocardiogram.
- Changes in the rate of mitral annulus velocity (e') [6 Months]
e' is reported in centimeters per second (cm/s) based on a subject performed echocardiogram
- Changes in the ratio of transmitral early peak velocity (E) by pulsed wave Doppler over e' (E/e') [6 Months]
E/e' is reported as an integer based on the transmitral early peak velocity (E) over the mitral annulus velocity (e') from a subject performed echocardiogram.
- PH-HFpEF Only Hemodynamics: Changes in Right Atrial Pressure (RAP) [6 Months]
This is determined by a combination equation subtracting the venous return (VR) from the central venous pressure (CVP), reported in millimeters of mercury (mmHg) from the echocardiogram.
- PH-HFpEF Only Hemodynamics: Changes in Pulmonary Artery Pressure (PAP) [6 Months]
This is calculated from systolic, by Tricuspid Regurgitation maximum (TRmax) and diastolic, by Pulmonary Regurgitation-end velocity (PR-end) pulmonary artery pressures, reported in millimeters of mercury (mmHg) from the echocardiogram.
- PH-HFpEF Only Hemodynamics: Changes in Pulmonary Artery Occlusive Pressure (PAOP) [6 Months]
This is determined by the pressure value of the pulmonary artery once it's occluded during a Right Heart Catheterization (RHC), measured in millimeters of mercury (mmHg).
- PH-HFpEF Only Hemodynamics: Changes in Pulmonary Vascular Resistance (PVR) [6 Months]
Left Atrial Pressure (LAP), Pulmonary Artery Pressure (PAP) and Cardiac Output (CO) are combined to report the PVR in Wood Units (WU) from a Right Heart Catheterization (RHC).
- PH-HFpEF Only Hemodynamics: Changes in Cardiac Output (CO) [6 Months]
Stoke Volume (SV) and Heart Rate (HR) are combined to report CO in liters per minute (L/min) from the right heart catheterization.
- PH-HFpEF Only Hemodynamics: Changes in Cardiac Index (CI) [6 Months]
Cardiac Output (CO) and Body Surface Area (BSA) are combined to report CI in liters per minute per meters squared (L/min/m^2) from a Right Heart Catherization (RHC).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adults (age 21-80) who meet clinical signs and symptoms of heart failure based on clinical assessment.
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The subject must meet at least one of the following hemodynamic criteria for HFpEF of PH-HFpEF by right heart catheterization (RHC) within 6 months of screening visit;
A) HFpEF:
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At rest: mean pulmonary artery occlusions pressure (PAOP) > 15, pulmonary vascular resistance (PVR) < 3 Wood Units, or
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HFpEF with fluid challenge, defined as increase in PAOP post 500 cc fluid bolus: mean PAOP > 18, PVR < 3 Wood Units, or
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HFpEF with exercise, defined as peak mean PAOP > 17, PVR < 3 Wood Units if age < 50 or peak mean PAOP > 19 and PVR < 3 Wood Units if age >= 50
B) PH-HFpEF:
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At rest: mean pulmonary artery occlusion pressure (PAOP) > 15, mean pulmonary artery pressure (PAP) >= 25, pulmonary vascular resistance (PVR) > 3 Wood Units, or
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PH-HFpEF with fluid challenge, defined as increase in PAOP post 500 cc fluid bolus: mean PAOP > 18, mean PAP >= 25, PVR > 3 Wood Units, or
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PH-HFpEF with exercise, defined as peak mean PAOP > 17, peak mean PAP > 30, peak PVR > 1.34 Wood Units if age < 50 or peak mean PAOP > 19, peak mean PAP > 33, and PVR < 2.1 Wood Units if age >= 50
- The subject also must meet criteria for metabolic syndrome, defined as: Abdominal obesity (BMI > 30 kg/m2 or abdominal obesity, waist circumference > 102 cm men, > 88 cm women) AND 2 of the following;
- Currently being treated for systemic hypertension or blood pressure (BP) >= 135/85 b. Glucose intolerance with diagnosis of type 2 diabetes, or fasting blood glucose 110-125 mg/dL or hemoglobin A1c > 6% c. Triglycerides >= 150, or on treatment for high triglycerides d. HDL < 40 men, < 50 women, or on treatment for high triglycerides
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If the subject is on pulmonary hypertension specific vasodilators, they must be on stable medical therapy without changes to pulmonary vasodilator medication within 3 months prior to screening visit.
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The subject must have also had a cardiopulmonary exercise test within 6 months of screening visit.
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The subject must have also had an echocardiogram within 6 months of screening visit.
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The subject must have demonstrated stable weight (less that 5% weight loss) 3 months prior to screening visit. (They cannot already be losing weight).
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The subject owns and uses a smartphone or tablet.
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Must speak English
Exclusion Criteria:
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The subject is already on a significant weight loss trajectory prior to study entry.
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The subject cannot be on an alternative diet plan or strategy (e.g., Weight Watchers, Nutrisystem, Ornish).
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Left ventricular ejection fraction < 50%.
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Severe valvular disease by echocardiogram or dysfunctional prosthetic valve.
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Active pericardial disease (moderate or large pericardial effusion or constrictive pericarditis).
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Active coronary ischemia defined by abnormal stress test, angiogram, or coronary CT angiography per investigator.
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Prolonged corrected QT interval (QTc) > 450 ms
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Significant lung disease on pulmonary function tests (PFT's) within the 6 months of screening visit, (Both post-bronchodilator values and pre-bronchodilator values must meet exclusion criteria. If either post- or pre-bronchodilator values do not, the subject may be included) defined as either:
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Irreversible obstructive airways disease (post-bronchodilator forced expiratory volume/forced vital capacity (FEV1/FVC) < 70% predicted) or
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Restrictive lung disease (FVC < 70% predicted. If total lung capacity (TLC) is >= 70%, it is acceptable to have an FVC of < 70%) or
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More than mild radiographic pulmonary disease as determine don CT scan within the past 2 years per investigator.
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History of non-adherence to diuretics within 3 months of screening visit.
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History or recurrent severe hypokalemia, potassium < 3.0 mg/dL.
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History of kidney stones, gout, or gallbladder disease unless in the opinion of the investigator it will not impact the safety of the patient
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C-peptide < 0.5 ng/mL (increased risk of diabetic ketoacidosis (DKA))
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Uncorrected anemia (hemoglobin < 10 g/dL).
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Unable to participate in the comprehensive ketogenic diet program, including biometric data acquisition and data entry (glucometer self-stick and smartphone use).
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Unable or unwilling to prepare meals for self.
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Unable to perform quantitative cardia testing regimen (cardiopulmonary exercise testing, 6-minute walk).
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Subject is pregnant or planning to become pregnant in the next 14 months.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Jewish Health and University of Colorado Denver | Denver | Colorado | United States | 80206 |
| 2 | Saint Joseph Hospital | Denver | Colorado | United States | 80218 |
Sponsors and Collaborators
- National Jewish Health
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HS-3243 Keto