Inorganic NItrate and EXercise Performance in Heart Failure (iNIX-HF): Dose Response

• Status: Recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to do the work that is necessary and sufficient for setting up an appropriate multi-center, randomized clinical trial (RCT) of a new therapy for heart failure: inorganic nitrate. The investigators will first determine the effects and palatability of ~12.8mmol KNO3 (an oral pill) as compared to the roughly equivalent amount of nitrate in 2 beetroot juice (BRJ) Sports Shots (by James White Drinks). Next, the investigators will determine the effects of inorganic nitrate (KNO3 in an oral pill format) on blood pressure, blood nitrate levels, breath nitric oxide (NO) levels, and exercise performance in a dose-response study. Third, the investigators will perform a small phase II chronic treatment study that will allow them to determine the best primary endpoint and the numbers of patients the investigators will need to study in the large, multi-center RCT to follow this project. In the small study and in the RCT to follow, the investigators will determine whether inorganic nitrate can improve aerobic exercise capacity, muscle power, and speed of muscle contraction, and lessen the effort of breathing during exercise.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine

Criteria

Inclusion Criteria:

1. Sex: females and males

2. Age: at least 18 years and less than 75 years

3. Diagnosis of heart failure with reduced ejection fraction (NYHA II-IV)

4. Ejection fraction <45% as determined on an imaging study within 12 mo of enrollment

5. Stable medical therapy - defined by no addition or removal (or change of more than 100%) of the following: beta-adrenergic blockade, angiotensin converting enzyme (ACE) inhibitors, or angiotensin receptor blocker (ARB or aldosterone antagonists) for 30 days prior to enrolment

Exclusion Criteria:

1. "Vulnerable populations" as defined by the U.S. Department of Health and Human Services, such as prisoners and children

2. Pharmacologic, organic nitrate therapy within the last 3 months

3. Major orthopedic, psychiatric, neurological, or other conditions that would impair performance of the exercise tests in this study

4. Atrial fibrillation/flutter

5. Estimated glomerular filtration rate < 50 ml/min on most recent clinical laboratories

6. Systolic blood pressure < 95 mmHg or >180 mmHg at consent

7. Diastolic blood pressure <40 mmHg or >100 mmHg at consent

8. Previous adverse reaction to nitrates necessitating withdrawal of therapy

9. Treatment with phosphodiesterase inhibitors within the last 3 months (patient must also be willing to not take them for the duration of the trial).

10. Ejection fraction > 45%

11. Primary hypertrophic cardiomyopathy

12. Infiltrative cardiomyopathy (e.g., amyloid)

13. Active myocarditis

14. Complex congenital heart disease

15. Active collagen vascular disease

16. Active angina/ischemia from epicardial coronary disease

17. Percutaneous coronary intervention, new bi-ventricular pacing, or coronary artery bypass grafting within the past 3 months

18. More than mild mitral or aortic stenosis

19. Valvular heart disease with severe regurgitation of any valve.

20. Acute or chronic severe liver disease as evidenced by encephalopathy, international normalized ratio (INR) >1.7 without anticoagulation therapy, or variceal bleeding

21. Patients requiring exogenous oxygen at rest or for exercise

22. Terminal disease (other than heart failure) with expected survival < 1 y

23. Enrollment in another therapeutic trial during the period of the study

24. Pregnancy