Inorganic Nitrate for Heart Failure

No longer recruiting at 1 trial location

Overseen By Deb Koudelis

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Washington University School of Medicine

Must be taking: Beta-blockers, ACE inhibitors, ARBs

Must not be taking: Organic nitrates, Phosphodiesterase inhibitors

Disqualifiers: Atrial fibrillation, Severe liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether an oral pill of inorganic nitrate (KNO3, or Potassium Nitrate) can enhance exercise capacity and muscle power in people with heart failure. It compares the effects of this pill to a similar amount of nitrate found in beetroot juice. Researchers will examine changes in blood pressure and exercise performance to determine if the treatment eases breathing during exercise. Individuals diagnosed with heart failure who have been stable on their current medication for at least 30 days are eligible to participate. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking heart failure treatment research.

Will I have to stop taking my current medications?

The trial requires that your current heart failure medications remain stable, meaning no major changes in dosage or type for 30 days before joining. If you're on phosphodiesterase inhibitors, you must stop them for the trial duration.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research suggests that potassium nitrate (KNO3) might be safe for people with heart failure. Studies have shown that KNO3 is generally well-tolerated. In one study, heart failure patients who took KNO3 experienced better exercise performance and quality of life without major side effects. Another study found that KNO3 could help improve exercise ability in these patients. While these results are encouraging, the treatment remains in early testing stages, focusing on safety and how the body processes it. So far, results suggest that KNO3 is likely safe, but more research is needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for heart failure?

Researchers are excited about using potassium nitrate (KNO3) for heart failure because it offers a novel approach by boosting nitric oxide levels in the body. Unlike standard treatments like ACE inhibitors or beta-blockers, which primarily focus on reducing heart strain and controlling symptoms, KNO3 directly enhances blood flow and oxygen delivery by widening blood vessels. This unique mechanism could potentially lead to faster and more effective symptom relief for patients. Additionally, the oral administration of KNO3 in capsule form makes it easy to integrate into daily routines.

What evidence suggests that this treatment might be an effective treatment for heart failure?

Research has shown that potassium nitrate (KNO3) might help people with heart failure exercise more easily. Studies have found that it can improve exercise ability and oxygen use in individuals with heart problems. KNO3 likely works by increasing nitric oxide, which relaxes blood vessels and improves blood flow, making exercise feel easier. Some research also suggests that KNO3 might help people exercise longer and enhance their quality of life. In this trial, participants will receive either a 10mmol or 20mmol dose of KNO3, with the dose order randomized, to evaluate its effectiveness. Overall, potassium nitrate appears promising in aiding those with heart failure to exercise more effectively. ^{1 2 4 5 6}

Who Is on the Research Team?

Linda R Peterson, MD

Principal Investigator

Washington University School of Medicine

Andrew R Coggan, PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with heart failure characterized by reduced ejection fraction (NYHA II-IV) and stable on certain heart medications. Excluded are pregnant individuals, those with severe liver disease, recent other nitrate treatments, complex heart issues, or conditions affecting exercise test performance.

Inclusion Criteria

My heart medication doses haven't changed significantly in the last 30 days.

My heart's pumping ability is below 45%.

I have been diagnosed with heart failure where my heart doesn’t pump well.

Exclusion Criteria

I have inflammation of the heart muscle.

Pregnancy

My kidney function is reduced, with a filtration rate under 50 ml/min.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Visit 1

Participants receive 2 capsules containing either 10 or 20 mmol of potassium nitrate (KNO3) and undergo various assessments including blood pressure, plasma nitrite levels, and nitric oxide breath analysis

1 day

1 visit (in-person)

Washout Period

Participants undergo a 7-day washout period between dose visits

1 week

Dose Visit 2

Participants receive the alternate dose of potassium nitrate (KNO3) and repeat the same assessments as Dose Visit 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KNO3

Trial Overview The study tests if potassium nitrate pills can improve blood pressure, blood nitrate levels, breath NO levels, and exercise performance in heart failure patients. It compares the effects of these pills to beetroot juice shots and looks at different doses.

How Is the Trial Designed?

Group I: 20mmol KNO3 Experimental Treatment 1 Intervention

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.

Group II: 10mmol KNO3 Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Nitrates, such as isosorbide dinitrate, can improve heart failure symptoms and exercise tolerance by reducing cardiac filling pressures and increasing cardiac output, as shown in studies combining them with digoxin and diuretics.

Long-term use of nitrates has been associated with improved survival rates and left ventricular ejection fraction, suggesting they may help prevent harmful changes in the heart's structure, although the best dosing strategies for heart failure patients are still being researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of action and efficacy of nitrates in heart failure. Cohn, JN.[2019]

In a study of 19,047 patients with heart failure and preserved ejection fraction (HFpEF), nitrates did not improve all-cause mortality or reduce heart failure hospitalizations, showing a hazard ratio of 1.06 when compared to untreated patients.

Despite initial expectations that nitrates could enhance heart function, the data indicated that their use was associated with worse outcomes, including a higher risk of hospitalization and lower event-free survival rates in the matched cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Use of Long-Acting Nitrates and Outcomes in Heart Failure With Preserved Ejection Fraction. Lim, SL., Benson, L., Dahlström, U., et al.[2017]

In a pilot study involving 9 patients with heart failure, ingestion of inorganic nitrate (NO3 (-)) from beetroot juice significantly increased nitric oxide production and improved muscle power, particularly in knee extension.

The study found that dietary NO3 (-) led to a 9% to 11% increase in peak knee extensor power and maximal velocity, with no adverse effects reported, suggesting it could be a safe and effective intervention for enhancing muscle function in heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial. Coggan, AR., Leibowitz, JL., Spearie, CA., et al.[2018]

A pilot trial is being conducted to evaluate the feasibility of using oral sodium nitrate as a treatment for acute heart failure (AHF), which is characterized by impaired vasorelaxation and reduced nitric oxide levels.

The study aims to determine if sodium nitrate can increase levels of nitric oxide precursors in the blood and improve vasorelaxation without causing significant drops in blood pressure, potentially offering a new treatment option for AHF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inorganic nitrate as a treatment for acute heart failure: a protocol for a single center, randomized, double-blind, placebo-controlled pilot and feasibility study. Falls, R., Seman, M., Braat, S., et al.[2018]

New potassium binders (NPBs) significantly improve the optimization of mineralocorticoid receptor antagonists (MRAs) in heart failure patients, reducing the occurrence of hyperkalaemia and allowing more patients to reach target doses of MRAs.

While NPBs show promise in enhancing MRA therapy, they do not significantly affect the optimization of other heart failure medications like ACE inhibitors or ARBs, and they may increase the risk of hypokalaemia, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis. Abuelazm, M., Badr, A., Turkmani, M., et al.[2023]

In a study involving rats with chronic heart failure (CHF), a potassium-supplemented diet significantly reduced the incidence of cardiac arrhythmias and improved cardiac sympathetic tone compared to a normal diet over a 6-week period.

The potassium supplementation also restored baroreflex function and improved irregular breathing patterns, indicating that increasing dietary potassium may help alleviate cardiorespiratory dysfunction in CHF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of enriched-potassium diet on cardiorespiratory outcomes in experimental non-ischemic chronic heart failure. Schwarz, KG., Pereyra, KV., Toledo, C., et al.[2022]

Nitroglycerin and its derivatives effectively treat severe heart failure by reducing the heart's preload and afterload, which improves cardiac output and alleviates symptoms for patients.

Intravenous nitrates are particularly useful in acute situations like myocardial infarction and worsening left ventricular failure, while oral and transdermal forms are prescribed for chronic heart failure in advanced stages (NYHA class III and IV).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of nitroglycerin in the treatment of congestive heart failure]. Curyło, AM.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39693096/

Potassium Nitrate in Heart Failure With Preserved Ejection ... Importance: Nitric oxide deficiency may contribute to exercise intolerance in patients with heart failure with preserved ejection fraction ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02840799

NCT02840799 | Effect of KNO3 Compared to KCl on ... This trial seeks to assess if potassium nitrate (KNO3) therapy improves exercise capacity and oxygen uptake in heart failure patients with preserved ejection ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2451865423001540

The inorganic NItrate and eXercise performance in Heart ... The inorganic NItrate and eXercise performance In Heart Failure (iNIX-HF) phase II clinical trial will further evaluate the effectiveness of dietary NO3− as a ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27927683/

Pharmacokinetics and Pharmacodynamics of Inorganic Nitrate ... Conclusions: KNO3 is potentially well tolerated and improves exercise duration and quality of life in heart failure with preserved ejection ...

5. eurjmedres.biomedcentral.com eurjmedres.biomedcentral.com/articles/10.1186/s40001-025-02916-6

Systematic review and meta-analysis of nitrates/nitrites in ... Dietary nitrate increases VO2peak and performance but does not alter ventilation or efficiency in patients with heart failure with reduced ...

6. ahajournals.org ahajournals.org/doi/10.1161/circresaha.116.309832

Pharmacokinetics and Pharmacodynamics of Inorganic ... KNO3 is potentially well tolerated and improves exercise duration and quality of life in heart failure with preserved ejection fraction. This ...