Clinical trial NCT04942548: Reverse HFpEF: Ketogenic Reversal of Heart Failure With Preserved Ejection Fraction Study
Official title: Reverse HFpEF: Ketogenic Reversal of Heart Failure With Preserved Ejection Fraction Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: obese
keto
diet
cardiac
Lead sponsor: National Jewish Health
Sponsor class: OTHER
First posted: 2021-06-28
Enrollment: 16
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Adults (age 21-80) who meet clinical signs and symptoms of heart failure based on clinical assessment.
* 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:

1. At rest: mean pulmonary artery occlusions pressure (PAOP) \> 15, pulmonary vascular resistance (PVR) \< 3 Wood Units, or
2. HFpEF with fluid challenge, defined as increase in PAOP post 500 cc fluid bolus: mean PAOP \> 18, PVR \< 3 Wood Units, or
3. 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:

1. At rest: mean pulmonary artery occlusion pressure (PAOP) \> 15, mean pulmonary artery pressure (PAP) \>= 25, pulmonary vascular resistance (PVR) \> 3 Wood Units, or
2. 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
3. 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;

a. 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

* 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.
* The subject must have also had a cardiopulmonary exercise test within 6 months of screening visit.
* The subject must have also had an echocardiogram within 6 months of screening visit.
* The subject must have demonstrated stable weight (less that 5% weight loss) 3 months prior to screening visit. (They cannot already be losing weight).
* The subject owns and uses a smartphone or tablet.
* Must speak English

Exclusion Criteria:

* The subject is already on a significant weight loss trajectory prior to study entry.
* The subject cannot be on an alternative diet plan or strategy (e.g., Weight Watchers, Nutrisystem, Ornish).
* Left ventricular ejection fraction \< 50%.
* Severe valvular disease by echocardiogram or dysfunctional prosthetic valve.
* Active pericardial disease (moderate or large pericardial effusion or constrictive pericarditis).
* Active coronary ischemia defined by abnormal stress test, angiogram, or coronary CT angiography per investigator.
* Prolonged corrected QT interval (QTc) \> 450 ms
* 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:

  1. Irreversible obstructive airways disease (post-bronchodilator forced expiratory volume/forced vital capacity (FEV1/FVC) \< 70% predicted) or
  2. Restrictive lung disease (FVC \< 70% predicted. If total lung capacity (TLC) is \>= 70%, it is acceptable to have an FVC of \< 70%) or
  3. More than mild radiographic pulmonary disease as determine don CT scan within the past 2 years per investigator.
* History of non-adherence to diuretics within 3 months of screening visit.
* History or recurrent severe hypokalemia, potassium \< 3.0 mg/dL.
* History of kidney stones, gout, or gallbladder disease unless in the opinion of the investigator it will not impact the safety of the patient
* C-peptide \< 0.5 ng/mL (increased risk of diabetic ketoacidosis (DKA))
* Uncorrected anemia (hemoglobin \< 10 g/dL).
* Unable to participate in the comprehensive ketogenic diet program, including biometric data acquisition and data entry (glucometer self-stick and smartphone use).
* Unable or unwilling to prepare meals for self.
* Unable to perform quantitative cardia testing regimen (cardiopulmonary exercise testing, 6-minute walk).
* Subject is pregnant or planning to become pregnant in the next 14 months.

Primary outcomes:
measure: MLHFQ Questionnaire
timeFrame: 6 Months
measure: PAH-SYMPACT Questionnaire
timeFrame: 6 Months
Secondary outcomes:
measure: Change in Metabolic Health: Weight
timeFrame: 6 Months
measure: Change in Metabolic Health: Glucose
timeFrame: 6 Months
measure: Change in Metabolic Health: Insulin
timeFrame: 6 Months
measure: Change in Metabolic Health: Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
timeFrame: 6 Months
measure: Change in Metabolic Health: Albumin
timeFrame: 6 Months
measure: Change in Metabolic Health: Bilirubin total
timeFrame: 6 Months
measure: Change in Metabolic Health: Alanine Transaminase (ALT)
timeFrame: 6 Months
measure: Change in Metabolic Health: Aspartate Aminotransferase (AST)
timeFrame: 6 Months
measure: Change in Metabolic Health: Alkaline Phosphatase (ALP)
timeFrame: 6 Months
measure: Change in Metabolic Health: High Sensitivity C-Reactive Protein (HS-CRP)
timeFrame: 6 Months
measure: Change in Metabolic Health: Triglycerides
timeFrame: 6 Months
measure: Change in Metabolic Health: High Density Lipoprotein (HDL)
timeFrame: 6 Months
measure: Change in Metabolic Health: Hemoglobin A1c
timeFrame: 6 Months
measure: Change in Metabolic Health: Body Mass Index (BMI)
timeFrame: 6 Months
measure: Changes in Physical Function: 6 Minute Walk Test (6MWT)
timeFrame: 6 Months
measure: Changes in Physical Function: Maximum Oxygen Consumption (VO2max)
timeFrame: 6 Months
measure: Changes in Physical Function: Maximum Work
timeFrame: 6 Months
measure: Changes in Physical Function: 30 Second Sit-to-Stand test (30s STS)
timeFrame: 6 Months
measure: Changes in Physical Function: Leg Press - 1 Repetition Maximum
timeFrame: 6 Months
measure: Changes in Physical Function: Chest Press - 1 Repetition Maximum
timeFrame: 6 Months
measure: Changes in Physical Function: Leg Extension - 1 Repetition Maximum
timeFrame: 6 Months
measure: Cardiac Remodeling: Changes in the Left Ventricle (LV) size
timeFrame: 6 Months
measure: Cardiac Remodeling: Changes in the Left Ventricle (LV) thickness
timeFrame: 6 Months
measure: Cardiac Remodeling: Changes in the Left Ventricle (LV) mass
timeFrame: 6 Months
measure: Cardiac Remodeling: Changes in Left Atrium (LA) size
timeFrame: 6 Months
measure: Cardiac Remodeling: Changes in Inferior Vena Cava (IVC) size
timeFrame: 6 Months
measure: Cardiac Remodeling: Changes in estimated Right Atrial Pressure (RAP)
timeFrame: 6 Months
measure: Cardiac Remodeling: Changes in Right Ventricle Systolic Pressure (RVSP)
timeFrame: 6 Months
measure: Changes in the rate of mitral annulus velocity (e')
timeFrame: 6 Months
measure: Changes in the ratio of transmitral early peak velocity (E) by pulsed wave Doppler over e' (E/e')
timeFrame: 6 Months
measure: PH-HFpEF Only Hemodynamics: Changes in Right Atrial Pressure (RAP)
timeFrame: 6 Months
measure: PH-HFpEF Only Hemodynamics: Changes in Pulmonary Artery Pressure (PAP)
timeFrame: 6 Months
measure: PH-HFpEF Only Hemodynamics: Changes in Pulmonary Artery Occlusive Pressure (PAOP)
timeFrame: 6 Months
measure: PH-HFpEF Only Hemodynamics: Changes in Pulmonary Vascular Resistance (PVR)
timeFrame: 6 Months
measure: PH-HFpEF Only Hemodynamics: Changes in Cardiac Output (CO)
timeFrame: 6 Months
measure: PH-HFpEF Only Hemodynamics: Changes in Cardiac Index (CI)
timeFrame: 6 Months
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Health and University of Colorado Denver
state: Colorado
city: Denver
country: United States
facility: Saint Joseph Hospital
state: Colorado
Study officials:
References: