A Study of Oral Nitrate in Adults With Pulmonary Hypertension With Heart Failure and Preserved Ejection Fraction (PMED)

Gladwin, Mark, MD

Status and phase

Completed

Phase 1

Conditions

Preserved Ejection Fraction

Pulmonary; Hypertension

Heart Failure

Treatments

Drug: 15N Nitrate

Drug: 14N Nitrate

Study type

Interventional

Funder types

NIH

Identifiers

NCT02980068

STUDY19120066

5P01HL103455 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This is an open-label, single-center study to examine distinguishing features of the structure and function of the oral and gut microbiome in healthy adult normal volunteers compared to volunteers with PH-HFpEF in the breakdown of oral nitrate.

Full description

We will enroll 60 Group II PH (PH-HFpEF) or Group I PAH patients and 60 matched healthy controls over three years. The Subjects will receive a single dose of one of the two study drugs, determined by whether they will participate in one study visit or two: 15N nitrate (1,000 mg) or 14N Sodium Nitrate: standard sodium nitrate, and all will receive one dose of CLA 3g. Twenty of the PH or PAH subjects and 20 of the control subjects willing to return for a follow up visit 24 hours after drug administration will receive 15N nitrate. All others will receive standard sodium nitrate. CLA will be obtained from GNC (General Nutrition Corporation) and given once.

Throughout the experiment, we will measure blood pressure, heart rate, and respiratory rate as well as co-oximetry. Plasma samples are collected at approximate times 0, 2, and 6 hrs post-drug administration. Urine will be collected at approximate times 0 and 6 hrs. We will examine plasma and urine nitrate and nitrite. The 40 subjects who return for a second visit 24 hours post-drug administration will provide an additional plasma and urine sample.

Enrollment

77 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

INCLUSION:

Male or female, 18 years of age or older
PH group: Pulmonary hypertension, hemodynamically defined by a mean PAP ≥ 25 mm Hg, and a TPG >= 12 at rest or during exercise as demonstrated on a right heart catheterization in the last 10 years
RHC Control group: Normal hemodynamics (mean PAP < 25 mm Hg, PCWP ≤ 15 mm Hg) on clinical right heart catheterization
Healthy Control group: Healthy patients with no evidence of pulmonary hypertension, respiratory or cardiac disease
Ability to provide written informed consent

EXCLUSION:

Use of systemic antibiotics and/or chlorhexidine mouthwash, within the previous three months
Use of immune suppression (chemotherapy, oral prednisone greater than 20mg per day, etc) with in the previous three months
Use of phosphodiesterase-5 inhibitors (tadalafil, sildenafil, etc) within 7 days before study drug administration
Current pregnancy or lactation
Uncontrolled systemic hypertension based on repeated measurement of sitting systolic blood pressure >185 mm Hg or sitting diastolic blood pressure >110 mm Hg at screening
Has chronic renal insufficiency as defined by serum creatinine >3 mg/dL at screening or requires dialytic support
Known history of left ventricular ejection fraction < 40% by multiple gated acquisition scan (MUGA), angiography, or echocardiography
History of atrial septostomy
Repaired or unrepaired congenital heart disease
Pericardial constriction
Restrictive or constrictive cardiomyopathy
Symptomatic coronary disease with demonstrable ischemia
Addition or change in dosing of hormonal contraception medications (OCP, IUD, Depo-Provera) in the past 4 weeks.
Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study or would prevent completion of the study
Active participation in other research studies with investigational drugs