Pharmacokinetics, Pharmacodynamics, and Impact of Inorganic Nitrate on Exercise in HFpEF
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|ClinicalTrials.gov Identifier: NCT02256345|
Recruitment Status : Completed
First Posted : October 3, 2014
Results First Posted : October 3, 2017
Last Update Posted : October 3, 2017
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:
- Determine the population-specific pharmacokinetics and dose of KNO3 that can be safely given to subjects with HFpEF.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Heart Failure Diastolic Heart Failure||Drug: KNO3 Drug: KCl||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Pharmacokinetics, Pharmacodynamics, and Impact of Inorganic Nitrate on Exercise in HFpEF|
|Study Start Date :||January 2015|
|Actual Primary Completion Date :||June 2016|
|Actual Study Completion Date :||June 2016|
Active Comparator: KNO3 active comparator
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
Other Name: Potassium Nitrate
Placebo Comparator: KCl placebo comparator
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
Other Name: Potassium Chloride
- Change in Peak Oxygen Uptake (VO2) From Baseline Upto 1 Week of Administration for Each Dose [ Time Frame: Baseline, end of week 1, end of week 2 ]Peak oxygen uptake (VO2) defined as the average value obtained during the last 30 seconds of exercise.
- Change in Vasodilatory Reserve for Each Dose [ Time Frame: Baseline, end of week 1, end of week 2 ]Percent change in peak vascular resistance from rest to peak exercise
- Change in Mitochondrial Oxidative Capacity for Each Dose [ Time Frame: Baseline, end of week 1, end of week 2 ]Percent change in oxidative capacity (oxyhemoglobin levels) before and after occlusion
- Change in Aortic Augmentation Index [ Time Frame: Baseline, end of week 1, end of week 2 ]Percent change in augmentation index, whereas augmentation index at each time point (visit) is defined as the amplitude of the second peak to the first peak of the aortic pulse wave form multiplied by 100: augmentation index = (P2/P1)×100.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02256345
|United States, Pennsylvania|
|Hospital of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Julio A Chirinos, MD||University of Pennsylvania|