AzTrials
AzTrials

Heart Failure With Preserved Ejection FractionPhase 2MPMANCT04913805

Matching Perfusion and Metabolic Activity in HFpEF

A Phase 2 study testing Potassium Nitrate, Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside and Potassium Chloride in people with Heart Failure With Preserved Ejection Fraction, run by University of Pennsylvania at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This study will test whether pharmacologic agents that increase perfusion [Potassium Nitrate (KNO3)], with and without additional supplements that may improve mitochondrial function [Propionyl-L-Carnitine (PLC) and Nicotinamide Riboside (NR)], improve submaximal exercise endurance and skeletal muscle oxidative… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Potassium Nitrate, Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside and Potassium Chloride
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
53 participants
Where
1 siteUnited States
Study dates
11 Oct 2021to 1 May 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • NYHA Class II-III symptoms
  • Left ventricular ejection fraction >= 50%
  • Stable medical condition for at least 2 weeks, as per investigator judgment
  • Prior or current evidence for elevated filling pressures as follows:
  • Mitral early (E)/mitral septal tissue annular (e') velocity ratio > 8, in the context of a septal e' velocity <=7, in addition to one of the following: i. Large left atrium (LA volume index > 34 mL/m2) ii. Chronic loop diuretic use for control of symptoms iii. Elevated natriuretic peptides within the past year (e.g. NTproBNP > 125 pg/mL in sinus rhythm or > 375 pg/mL if in atrial fibrillation) b. Mitral E/e' ratio > 14 at rest or during exercise c. Elevated invasively-determined filling pressures previously (resting left ventricular end-diastolic pressure >= 16 mm Hg or pulmonary capillary wedge pressure >= 15 mmHg; or PCWP/LVEDP >= 25 mmHg with exercise) d. Prior episode of acute heart failure requiring IV diuretics

Who cannot join

  • Age <18 years old
  • Pregnancy:
  • Treatment with organic nitrates or phosphodiesterase inhibitors that cannot be interrupted
  • Uncontrolled atrial fibrillation, as defined by a resting heart rate > 100 beats per minute at the time of the baseline assessment
  • Hemoglobin < 10 g/dL
  • Subject inability/unwillingness to exercise
Show all 25Show fewer
  • Moderate or greater left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), mild or greater mitral stenosis, severe right-sided valvular disease
  • Known hypertrophic, infiltrative, or inflammatory cardiomyopathy
  • Clinically significant pericardial disease, as per investigator judgment
  • Current angina due to clinically significant epicardial coronary disease, as per investigator judgment
  • Acute coronary syndrome or coronary intervention within the past 2 months
  • Primary pulmonary artery hypertension (WHO Group 1 Pulmonary Arterial Hypertension)
  • Clinically significant lung disease as defined by: Chronic Obstructive Pulmonary Disease meeting Stage III or greater GOLD criteria (FEV1<50%), treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, current use of supplemental oxygen aside from nocturnal oxygen for the treatment of obstructive sleep apnea, desaturation to <90% on the baseline maximal effort cardiopulmonary exercise test
  • Clinically-significant ischemia, as per investigator's judgement, on stress testing without either (1) subsequent revascularization, (2) an angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgment; (3) a follow-up 'negative' stress test, particularly when using a more specific technique (i.e., a negative perfusion imaging test following a 'positive' ECG stress test)
  • Left ventricular ejection fraction < 45% on a prior echocardiogram or cardiac MRI, unless the reduced LVEF occurred within the context of an uncontrolled supraventricular arrhythmia, with return of a normal ejection fraction following treatment of the arrhythmia
  • Significant liver disease impacting synthetic function or volume control (ALT/AST > 3x ULN, Albumin < 3.0 g/dL)
  • eGFR < 30 mL/min/1.73m^2
  • Methemoglobin > 5%
  • Serum potassium > 5.0 mEq/L
  • Severe right ventricular dysfunction
  • Baseline resting seated systolic blood pressure > 180 mmHg or < 100 mmHg
  • Persistently low (<100 mmHg) or high (>180 mmHg) seated blood pressure at the baseline visit
  • Orthostatic blood pressure response to the transition from supine to standing (>20 mmHg reduction in systolic blood pressure 2-3 minutes after standing)
  • Active participation in another study that utilizes an investigational agent (observational studies/registries allowed)
  • Any condition that, in the opinion of the investigator, will interfere with the performance and completion of the study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Melissa Fernand, MPH contact

2672536141

fernand@pennmedicine.upenn.edu

Cassandra Demastus, NP contact

4432719022

Cassandra.Demastus@Pennmedicine.upenn.edu

United States1 site, 1 recruiting

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Cassandra Demastus, NP, 4432719022, Cassandra.Demastus@Pennmedicine.upenn.edu

    Recruiting

Other trials in United States

About this study

This study will test whether pharmacologic agents that increase perfusion [Potassium Nitrate (KNO3)], with and without additional supplements that may improve mitochondrial function [Propionyl-L-Carnitine (PLC) and Nicotinamide Riboside (NR)], improve submaximal exercise endurance and skeletal muscle oxidative phosphorylation capacity (SkM OxPhos) in participants with Heart Failure with Preserved Ejection Fraction (HFpEF).

Read the detailed description

This study will test whether Potassium Nitrate (KNO3), with and without Propionyl-L-Carnitine (PLC) and Nicotinamide Riboside (NR), improves submaximal exercise endurance and skeletal muscle oxidative phosphorylation capacity (SkM OxPhos) in participants with Heart Failure with Preserved Ejection Fraction (HFpEF). Additionally, the study will test whether the response to supplemental oxygen during a standardized MRI assessment of skeletal muscle oxidative capacity can identify HFpEF individuals who preferentially will benefit from either KNO3 alone or the combination of pharmacologic agents (KNO3 + PLC + NR)

Being tested
Potassium Nitrate, Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside, Potassium Chloride

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Potassium NitrateDrug

    Also called KNO3

    Potassium Nitrate is the active intervention that may increase blood flow to exercising muscle

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

    Also called KNO3 + PLC + NR

    Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside will be used as a combination intervention to both increase blood flow (KNO3) and mitochondrial function (PLC + NR)

  • Potassium ChlorideOther

    Also called PCl

    Active control

Study groups in NCT04913805
Study groupRoleWhat they receive
Potassium NitrateActive comparatorPotassium Nitrate (KNO3) 6 mmol three times daily
Receives: Drug: Potassium Nitrate
Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide RibosideActive comparatorPotassium Nitrate (KNO3) 6 mmol three times daily + Propionyl-L-Carnitine (PLC) 1000 mg twice daily + Nicotinamide Riboside (NR) 300 mg three times daily
Receives: Drug: Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside
Potassium ChloridePlacebo comparatorPotassium Chloride (KCl) 6 mmol three times daily
Receives: Other: Potassium Chloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Submaximal Exercise Endurance

    Time to exhaustion while exercising at 75% of peak workload

    Measured: week 6

Secondary outcomes (7)

  1. Skeletal muscle oxidative capacity

    MRI assessment of skeletal muscle oxidative phosphorylation capacity

    Measured: week 6

  2. Vasodilatory Reserve

    Percent change in systemic vascular resistance at baseline vs exhaustion

    Measured: week 6

  3. Kansas City Cardiomyopathy Questionnaire Overall Summary Score

    Assess the impact of our interventions on quality of life

    Measured: week 6

  4. VO2 Kinetics

    Assess the impact of our interventions on the kinetics of oxygen consumption (VO2 kinetics) during exercise and recovery "On" and "Off" kinetics will be modeled during the submaximal exercise transient

    Measured: week 6

  5. Peak VO2

    maximal rate of oxygen consumption determined during the last 30s of exercise.

    Measured: week 6

  6. Steps per day

    we will use actigraphy to document the average number of steps taken per day during the final week of each interventional period. Assess the impact of our interventions on ambulatory physical activity

    Measured: week 6

  7. Skeletal muscle perfusion

    MRI assessment of skeletal muscle oxidative phosphorylation capacity

    Measured: week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2021
  2. Study start11 Oct 2021
  3. Primary completion1 May 2027 (estimated)
  4. Study completion1 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
3 interventions will be randomized and administered in a double-blind fashion
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
53 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04913805
Sponsor's protocol ID
844627
Acronym
MPMA
Status last verified
May 2026
First submitted
19 Apr 2021
Last updated
2 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Potassium Nitrate, Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside and Potassium Chloride in people with Heart Failure With Preserved Ejection Fraction, run by University of Pennsylvania at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Melissa Fernand, MPH (2672536141, fernand@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Submaximal Exercise Endurance (time frame: week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04913805.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.

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