Pharmacokinetics, Pharmacodynamics, and Impact of Inorganic Nitrate on Exercise in HFpEF

• Status: Completed
• Trial end date: 2016-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania

Criteria

Inclusion Criteria:

1. NYHA Class II-III symptoms.

2. LV EF > 50%.

3. Stable medical therapy for at least 1 month.

4. Evidence of significant diastolic dysfunction, meeting the European Society of Echocardiography criteria for HFpEF.

Exclusion Criteria

1. Any rhythm other than sinus with native conduction.

2. Inability to exercise.

3. Moderate or greater valvular disease.

4. Hypertrophic, infiltrative, or inflammatory cardiomyopathy.

5. Pericardial disease.

6. Current angina.

7. Acute coronary syndrome or coronary intervention within the past 2 months.

8. Primary pulmonary arteriopathy.

9. Clinically significant lung disease.

10. Ischemia on stress testing without subsequent revascularization.

11. Treatment with phosphodiesterase inhibitors that cannot be withheld.

12. Treatment with organic nitrates or allopurinol.

13. Significant liver disease impacting synthetic function or volume control.

14. Poor echocardiographic windows.

15. eGFR < 30 mL/min/m2 or Cr >2.5.

16. Current smoking.

17. Alcohol dependency.

18. History of Barret's esophagus.

19. G6PD deficiency

20. Methemoglobinemia - baseline methemoglobin level >3% prior to any study medication.