Blood Flow Improvement Drugs + Supplements for Heart Failure

(MPMA Trial)

Overseen By Cassandra Demastus, NP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must not be taking: Organic nitrates, Phosphodiesterase inhibitors

Disqualifiers: Pregnancy, Uncontrolled atrial fibrillation, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

53 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if certain drugs and supplements can help individuals with a type of heart failure improve exercise endurance and muscle function. Participants will receive either Potassium Nitrate, which may enhance blood flow, alone or combined with supplements that support cellular energy production. The study seeks individuals with moderate heart failure symptoms and a stable condition, meaning their heart function remains steady without major changes. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking organic nitrates or phosphodiesterase inhibitors if they cannot be interrupted. For other medications, the protocol does not specify, so it's best to discuss with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that potassium nitrate (KNO3) is usually well tolerated by people with heart failure who have a normal ejection fraction. Some studies suggest it can help people exercise longer and improve their quality of life, with few reports of major side effects.

When combined with propionyl-L-carnitine, nicotinamide riboside has been studied independently and found to be safe, even in high doses. It can increase levels of NAD+, a molecule important for energy production in cells.

This trial is in its early stages, so while there is some evidence of safety, more research is needed to fully understand any potential risks. Participants can feel reassured by the existing data but should stay informed and discuss any concerns with the research team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for heart failure because they focus on enhancing blood flow in a novel way. Unlike standard treatments like ACE inhibitors and beta-blockers that primarily manage symptoms and prevent disease progression, these study treatments aim to improve overall cardiovascular function. Potassium Nitrate is known to increase nitric oxide levels, which help dilate blood vessels and improve circulation. The combination treatment adds Propionyl-L-Carnitine and Nicotinamide Riboside, which are believed to boost cellular energy and further support heart function. This dual approach of enhancing blood flow and cellular energy is what sets these treatments apart and has researchers hopeful for better outcomes in heart failure management.

What evidence suggests that this trial's treatments could be effective for heart failure?

In this trial, participants will receive either Potassium Nitrate alone or a combination of Potassium Nitrate with Propionyl-L-Carnitine and Nicotinamide Riboside. Studies suggest that Potassium Nitrate might aid individuals with heart failure with preserved ejection fraction (HFpEF) by facilitating exercise through increased nitric oxide levels, which improve blood flow. However, some research has shown that Potassium Nitrate alone did not enhance exercise ability or quality of life for these patients.

Conversely, the combination of Potassium Nitrate with Propionyl-L-Carnitine and Nicotinamide Riboside aims to boost cellular energy production, potentially yielding better outcomes. These supplements are believed to support mitochondrial function, enhancing energy production for muscles. While early signs are promising, more evidence is needed to confirm their effectiveness. ^{2 3 6 7 8}

Who Is on the Research Team?

Payman Zamani, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults with Heart Failure with Preserved Ejection Fraction (HFpEF), who have been on stable heart medication for at least a month. They should have certain signs of heart stress, like specific ratios in their echocardiogram or history of acute heart failure. Excluded are those under 18, pregnant women, people with severe other diseases or conditions that could interfere with the study, and those taking conflicting medications.

Inclusion Criteria

You have signs of high pressure in your blood vessels.

Your heart has certain measurements and pressures that show it may not be working properly, or you've had a previous episode of acute heart failure requiring intravenous diuretics.

My current medication has been the same for at least 1 month.

Exclusion Criteria

Your methemoglobin level is higher than 5%.

Any condition that, in the opinion of the investigator, will interfere with the performance and completion of the study.

I have severe lung disease or need extra oxygen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Potassium Nitrate (KNO3) with or without additional supplements (Propionyl-L-Carnitine and Nicotinamide Riboside) to test improvements in exercise endurance and skeletal muscle oxidative phosphorylation capacity

6 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Potassium Nitrate
• Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside

Trial Overview

The study tests if Potassium Nitrate alone or combined with Propionyl-L-Carnitine and Nicotinamide Riboside can improve exercise endurance and muscle function in HFpEF patients. It compares these treatments to Potassium Chloride to see which is better at increasing blood flow and enhancing mitochondrial function.

How Is the Trial Designed?

Group I: Potassium Nitrate Active Control 1 Intervention

Potassium Nitrate (KNO3) 6 mmol three times daily

Group II: Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside Active Control 1 Intervention

Potassium Nitrate (KNO3) 6 mmol three times daily + Propionyl-L-Carnitine (PLC) 1000 mg twice daily + Nicotinamide Riboside (NR) 300 mg three times daily

Group III: Potassium Chloride Placebo Group 1 Intervention

Potassium Chloride (KCl) 6 mmol three times daily

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

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]

A survey of Heart Failure Society of America members found that nitrates are commonly used in chronic congestive heart failure (CHF) patients despite not being FDA-approved, with 90% using them for ischemic and 81% for nonischemic CHF.

Nitrates are primarily used to alleviate symptoms (96% of respondents), improve hemodynamics (74%), and enhance exercise tolerance (65%), but only a small percentage (14%) use them for left ventricular remodeling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey of the use of organic nitrates for the treatment of chronic congestive heart failure in the United States. Bitar, F., Akhter, MW., Khan, S., et al.[2015]

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]

Organic nitrates are effective in treating chronic congestive heart failure (CHF) by improving exercise capacity and reducing symptoms, and they can prolong life when combined with hydralazine in patients with mild-to-moderate symptoms.

However, many patients develop resistance to the hemodynamic effects of nitrates and early tolerance, which may limit their long-term benefits in CHF treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrate resistance and tolerance: potential limitations in the treatment of congestive heart failure. Elkayam, U., Mehra, A., Shotan, A., et al.[2019]

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]

In a study of 31 patients with acute heart failure (AHF), intravenous nicorandil significantly reduced levels of B-type natriuretic peptide (BNP) and showed a trend towards decreasing N-terminal-pro-BNP, indicating its efficacy in lowering cardiac stress markers.

Nicorandil improved hemodynamics in patients with high systolic blood pressure while being safe for those with low systolic blood pressure, suggesting it can be effectively used across different patient profiles in AHF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nicorandil therapy in patients with acute heart failure. Shirakabe, A., Hata, N., Yokoyama, S., et al.[2015]

Nitrates are effective in treating various cardiovascular conditions, such as stable and unstable angina, by dilating blood vessels and reducing heart workload, with their clinical effects primarily stemming from systemic venodilatation and decreased vascular resistance.

Nitrate therapy is generally safe and well-tolerated, with common side effects including headache and dizziness, and it is recommended to start with low doses and adjust as needed, making it an effective and inexpensive option for patients with cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitroglycerin and long-acting nitrates in clinical practice. Abrams, J.[2019]

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