Matching Perfusion and Metabolic Activity in HFpEF

NCT04913805 | Recruiting Phase 2 DMC

• 1 other identifier: 844627
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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 phosphorylation capacity (SkM OxPhos) in participants with Heart Failure with Preserved Ejection Fraction (HFpEF).

Conditions

Heart Failure With Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Submaximal Exercise Endurance

  Time to exhaustion while exercising at 75% of peak workload

  week 6

Secondary Outcomes (7)

• Skeletal muscle oxidative capacity

  week 6

• Vasodilatory Reserve

  week 6

• Kansas City Cardiomyopathy Questionnaire Overall Summary Score

  week 6

• VO2 Kinetics

  week 6

• Peak VO2

  week 6

Other Outcomes (1)

• Change in Skeletal Muscle Oxidative Capacity

  <4 hours in between MRIs

Study Arms (3)

Potassium Nitrate

ACTIVE COMPARATOR

Potassium Nitrate (KNO3) 6 mmol three times daily

Drug: Potassium Nitrate

Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside

ACTIVE COMPARATOR

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

Drug: Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside

Potassium Chloride

PLACEBO COMPARATOR

Potassium Chloride (KCl) 6 mmol three times daily

Other: Potassium Chloride

Interventions

Potassium Nitrate DRUG

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

Also known as: KNO3

Potassium Nitrate

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

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)

Also known as: KNO3 + PLC + NR

Potassium Nitrate + Propionyl-L-Carnitine + Nicotinamide Riboside

Potassium Chloride OTHER

Active control

Also known as: PCl

Potassium Chloride

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Interventions

potassium nitrate; nicotinamide-beta-riboside; Potassium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Potassium Compounds

Study Officials

• Payman Zamani, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa Fernand, MPH

CONTACT

2672536141; fernand@pennmedicine.upenn.edu

Cassandra Demastus, NP

CONTACT

4432719022; Cassandra.Demastus@Pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: all personnel will be masked except for the IDS pharmacist dispensing the drugs
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 3 interventions will be randomized and administered in a double-blind fashion

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: June 4, 2021
• Study Start: October 11, 2021
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 23, 2025

Record last verified: 2025-05

Locations

US (1)