Inorganic NItrate and EXercise Performance in Heart Failure (iNIX-HF): Dose Response
| Status: | Recruiting |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 74 |
| Updated: | 1/2/2019 |
| Start Date: | October 31, 2017 |
| End Date: | December 2025 |
| Contact: | Deb Koudelis |
| Email: | delanod@wustl.edu |
| Phone: | 314-747-3876 |
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.
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.
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.
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.
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
We found this trial at
1
site
660 S Euclid Ave
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Linda R Peterson, MD
Phone: 314-747-3839
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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