Inorganic NItrate and EXercise Performance in Heart Failure (iNIX-HF): Dose Response
Ключови думи
Резюме
Описание
1. Subjects will be patients with Heart Failure (HF).
2. All subjects will be consented.
3. All subjects will give permission for the investigators to review their medical records.
4. After consenting to participate, subjects will be instructed to refrain from spitting or the use of an antibacterial mouthwash, antacids, proton pump inhibitors, or chewing gum during the morning of each clinic visit.
5. Subjects will have a physical examination.
6. Subjects will undergo transthoracic echocardiographic imaging at rest (unless they had this performed within the past 6 months).
7. Subjects will be asked to undergo a mouth swab for bacterial DNA analyses.
8. Subjects will be asked to answer questionnaires regarding their medical health (basic health questionnaire, Minnesota living with heart failure questionnaire, a combined fatigue questionnaire.
9. Dose visit 1: Subjects will receive 2 capsules containing either 10 or 20 mmol of potassium nitrate (KNO3).
10. Before and at 3 hourly time points after receiving the KNO3, subjects will undergo phlebotomy for plasma nitrate and nitrite levels, will have their blood pressure measured, and will blow into a small machine to assess the amount of nitric oxide in their breath.
11. Exercise Test 1: Subjects will complete measurements of leg muscle power by doing knee extension exercises on a dynamometer (a device that measures voluntary muscle force production while controlling the speed of movement).
12. Exercise Test 2: Subjects complete a measurement of peak aerobic capacity (VO2peak) while walking on a treadmill and breathing into a mouthpiece. Blood pressure, heart rate and heart rhythm will be monitored during this test.
13. Subjects will undergo a 7 d washout period.
14. Dose visit 2: Subjects will receive 2 capsules containing either 10 or 20 mmol of KNO3 (whichever dose they did not receive at dose visit 1). They will repeat the same assessments listed above in 10, 11, and 12.
Дати
| Последна проверка: | 12/31/2019 |
| Първо изпратено: | 05/24/2016 |
| Очаквано записване подадено: | 06/06/2016 |
| Първо публикувано: | 06/12/2016 |
| Изпратена последна актуализация: | 01/19/2020 |
| Последна актуализация публикувана: | 01/21/2020 |
| Действителна начална дата на проучването: | 10/30/2017 |
| Приблизителна дата на първично завършване: | 12/30/2023 |
| Очаквана дата на завършване на проучването: | 12/30/2025 |
Състояние или заболяване
Интервенция / лечение
Drug: Aim 1. KNO3 dose response
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| Experimental: Aim 1. KNO3 dose response Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 or 20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 or 20 mmol KNO3) during dose visit 2. The dose order will be randomized. | Drug: Aim 1. KNO3 dose response Potassium nitrate (KNO3) will be given orally in 2 gelatin capsules, which will be compounded by the Barnes-Jewish Hospital Pharmacy. The doses are 10 mmol and 20 mmol KNO3. |
Критерии за допустимост
| Възрасти, отговарящи на условията за проучване | 18 Years Да се 18 Years |
| Полове, допустими за проучване | All |
| Приема здрави доброволци | Да |
| Критерии | 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 |
Резултат
Първични изходни мерки
1. VO2peak [acute - 2.5 hours post dose]
Вторични изходни мерки
1. Peak muscle power [acute - 2 hours post dose]
2. Blood nitrate and blood nitrite levels [time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose)]
3. Breath nitric oxide (NO) level [time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose)]
