Reverse HFpEF: Ketogenic Reversal of Heart Failure With Preserved Ejection Fraction Study

NCT04942548 | Completed

• 1 other identifier: HS-3243 Keto
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

Heart Failure

Keywords

obese; keto; diet; cardiac

Outcome Measures

Primary Outcomes (2)

• MLHFQ Questionnaire

  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

  6 Months

• PAH-SYMPACT Questionnaire

  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

  6 Months

Secondary Outcomes (36)

• Change in Metabolic Health: Weight

  6 Months

• Change in Metabolic Health: Glucose

  6 Months

• Change in Metabolic Health: Insulin

  6 Months

• Change in Metabolic Health: Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

  6 Months

• Change in Metabolic Health: Albumin

  6 Months

Study Arms (2)

HFpEF

EXPERIMENTAL

Patients diagnosed with obesity related heart failure with preserved ejection fraction(HFpEF)

Other: Ketogenic Diet

PH-HFpEF

EXPERIMENTAL

Patients diagnosed with obesity related pulmonary hypertension heart failure with preserved ejection fraction (PH-HFpEF)

Other: Ketogenic Diet

Interventions

Ketogenic Diet OTHER

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.

HFpEF; PH-HFpEF

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• At rest: mean pulmonary artery occlusions pressure (PAOP) \> 15, pulmonary vascular resistance (PVR) \< 3 Wood Units, or
• HFpEF with fluid challenge, defined as increase in PAOP post 500 cc fluid bolus: mean PAOP \> 18, PVR \< 3 Wood Units, or
• 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:
• At rest: mean pulmonary artery occlusion pressure (PAOP) \> 15, mean pulmonary artery pressure (PAP) \>= 25, pulmonary vascular resistance (PVR) \> 3 Wood Units, or
• 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
• 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.

You may not qualify if:

• 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
• Irreversible obstructive airways disease (post-bronchodilator forced expiratory volume/forced vital capacity (FEV1/FVC) \< 70% predicted) or
• Restrictive lung disease (FVC \< 70% predicted. If total lung capacity (TLC) is \>= 70%, it is acceptable to have an FVC of \< 70%) or
• 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).

Sponsors & Collaborators

• National Jewish Health: lead

Study Sites (2)

National Jewish Health and University of Colorado Denver

Denver, Colorado, 80206, United States

Location

Saint Joseph Hospital

Denver, Colorado, 80218, United States

Location

MeSH Terms

Conditions

Heart Failure; Obesity

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: June 28, 2021
• Study Start: July 25, 2019
• Primary Completion: July 24, 2023
• Study Completion: July 24, 2023
• Last Updated: April 3, 2024

Record last verified: 2024-04

Locations

US (2)