Conditions: Heart Failure Diastolic Heart Failure
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 12
Healthy volunteers: no

Brief summary:
This study will be performed to determine the safety, tolerability, and dose-response to inorganic nitrate on exercise capacity in HFpEF. There are two primary goals for this study:

1. Determine the population-specific pharmacokinetics and dose of KNO3 that can be safely given to subjects with HFpEF.
2. Determine if there is a dose-response effect of nitrate supplementation on exercise capacity, evidenced by peak oxygen consumption (peak VO2), and physiologic adaptations to exercise.

Detailed description:
This study randomized subjects to either placebo (n=3) or KNO3 (n=9) given a sequential dosing regimen: 6 mmol twice daily for 1 week followed by dose escalation to 6 mmol thrice daily for 1 week). Although a primary goal of the study was to assess the safety of KNO3 and within-group changes in various end points in KNO3-treated subjects, a small number of placebo-treated (PB, n=3) subjects were included only to assess for any potential training effect on repeated exercise and Kansas City Cardiomyopathy Questionnaire (KCCQ) measurements. Potassium chloride, given in equivalent doses, was used as the PB to account for differences in blood pressure or flow that could be attributed to potassium.

The study was initially designed to be single-blinded to allow the principal investigator to be aware of arm allocation because of potential concerns for methemoglobinemia with drug administration. One investigator, who was the primary investigator responsible for supervising all visits and measurements during the study, remained blinded to treatment allocation throughout the entirety of the study. All physiological and imaging data were analyzed in a double-blind manner.

Arms:
arm 1: KNO3 will be given at a dose of 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if well tolerated arm 2: KCl will be used as a placebo and will be given as 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if well tolerated

Interventions: intervention 1: KNO3 intervention 2: KCl
Intervention descriptions: intervention 1: Active Comparator intervention 2: Placebo Comparator

Protocol document: