Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF

Completed · Phase 2 · Has a placebo group

Conditions studied: Heart Failure

In brief

A randomized, double-blind, placebo-controlled crossover study to assess the effect of inorganic nitrite (NO2) on aerobic capacity (peak VO2) after four weeks of dosing. Approximately 100 participants will be enrolled in this 2\*2 crossover study.

Key facts

Study ID: NCT02742129
Run by: Adrian Hernandez
People needed: 105
Starts: 2016-08-10
Expected to finish: 2017-12-27
Last updated by the study team: 2019-03-13

Who can join

Age: 40 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Age ≥ 40 years
Symptoms of dyspnea (NYHA class II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea
EF ≥ 50% as determined on imaging study within 12 months of enrollment with no change in clinical status suggesting potential for deterioration in systolic function
One of the following :
Previous hospitalization for HF with radiographic evidence (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) of pulmonary congestion or
Catheterization documented elevated filling pressures at rest (PCWP ≥15 or LVEDP ≥18) or with exercise (PCWP ≥25) or
Elevated NT-proBNP (>400 pg/ml) or BNP(>200 pg/ml) or
Echo evidence of diastolic dysfunction/elevated filling pressures manifest by medial E/e' ratio≥15 and/or left atrial enlargement and chronic treatment with a loop diuretic for signs or symptoms of heart failure
Heart failure is primary factor limiting activity as indicated by answering # 2 to the following question:
My ability to be active is most limited by:
Joint, foot, leg, hip or back pain
Shortness of breath and/or fatigue and/or chest pain
Unsteadiness or dizziness
Lifestyle, weather, or I just don't like to be active
Peak VO2 ≤75% predicted with peak respiratory exchange ratio≥1.0 CPET Normal Values for Peak VO2* Criteria (ml/kg/min) 7. No chronic nitrate therapy or not using intermittent sublingual nitroglycerin (requirement for >1 SL nitroglycerin per week) within last 7 days 8. No daily use of phosphodiesterase 5 inhibitors or soluble guanylyl cyclase activators and willing to withhold prn use of phosphodiesterase 5 inhibitors for duration of study 9. Ambulatory (not wheelchair / scooter dependent) 10. Body size allows wearing of the accelerometer belt as confirmed by ability to comfortably fasten the test belt provided for the screening process (belt designed to fit persons with BMI 20-40 kg/m2 but belt may fit some persons outside this range) 11. Willingness to wear the accelerometer belt for the duration of the trial 12. Willingness to provide informed consent

You may not qualify if…

Recent (< 1 month) hospitalization for heart failure
Ongoing requirement for PDE5 inhibitor, organic nitrate or soluble guanylyl cyclase activators
Hemoglobin (Hgb) < 8.0 g/dl within 90 days prior to randomization
GFR < 20 ml/min/1.73 m2 within 90 days prior to randomization
Systolic blood pressure < 115 mmHg seated or < 90 mmHg standing just prior to test dose
Resting HR > 110 just prior to test dose
Previous adverse reaction to the study drug which necessitated withdrawal of therapy
Significant chronic obstructive pulmonary disease thought to contribute to dyspnea
Ischemia thought to contribute to dyspnea
Documentation of previous EF < 45%
Acute coronary syndrome within 3 months defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g., troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)
PCI, coronary artery bypass grafting, or new biventricular pacing within past 3 months
Primary hypertrophic cardiomyopathy
Infiltrative cardiomyopathy (amyloid)
Constrictive pericarditis or tamponade
Active myocarditis
Complex congenital heart disease
Active collagen vascular disease
More than mild aortic or mitral stenosis
Intrinsic (prolapse, rheumatic) valve disease with moderate to severe or severe mitral, tricuspid or aortic regurgitation
Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, INR > 1.7 in the absence of anticoagulation treatment
Terminal illness (other than HF) with expected survival of less than 1 year
Regularly (> 1x per week) swims or does water aerobics
Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months.
Inability to comply with planned study procedures

Where it is running

Emory University School of Medicine — Atlanta, Georgia, United States
Northwestern University — Chicago, Illinois, United States
Johns Hopkins Hospital — Baltimore, Maryland, United States
Tufts Medical Center — Boston, Massachusetts, United States
Massachusetts General Hospital — Boston, Massachusetts, United States
Brigham and Women's Hospital — Boston, Massachusetts, United States
Boston V.A. Healthcare System — West Roxbury, Massachusetts, United States
Mayo Clinic — Rochester, Minnesota, United States
University of Missouri Health System — Columbia, Missouri, United States
V.A St. Louis Health Care System — St Louis, Missouri, United States
Washington University School of Medicine — St Louis, Missouri, United States
Stony Brook University Medical Center — Stony Brook, New York, United States
Duke University Medical Center — Durham, North Carolina, United States
University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States
Metro Health System — Cleveland, Ohio, United States
Cleveland Clinic Foundation — Cleveland, Ohio, United States
Abington Memorial Hospital — Abington, Pennsylvania, United States
University of Pennsylvania Health System — Philadelphia, Pennsylvania, United States
Jefferson Medical College — Philadelphia, Pennsylvania, United States
The University of Vermont - Fletcher Allen Health Care — Burlington, Vermont, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.