Clinical trial NCT02980068: A Study of Oral Nitrate in Adults With Pulmonary Hypertension With Heart Failure and Preserved Ejection Fraction
Official title: An Open Label Study of Oral Nitrate in Adults With Pulmonary Hypertension With Heart Failure and Preserved Ejection Fraction (PH-HFpEF) and Normal Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary; Hypertension
Heart Failure
Preserved Ejection Fraction
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2016-12-02
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Change in nitrate level in urine
timeFrame: Urine collected approx 0 & 6 hours after drug administration
measure: Change in nitrate level in plasma
timeFrame: Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration
measure: Bacterial content of gut microbiome
timeFrame: Stool collected before drug administration
measure: Bacterial content of the oral microbiome
timeFrame: Saliva and tongue scraping will occur preceding administration of drug
measure: Change in nitrite level in urine
timeFrame: Urine collected approx 0 & 6 hours after drug administration
measure: Change in nitrite level in plasma
timeFrame: Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration
Secondary outcomes:
measure: Change in blood pressure
timeFrame: Frequently over 6 hour study visit
measure: Change in heart rate
timeFrame: Continuous over 6 hour study visit
measure: Change in respiratory rate
timeFrame: Continuous over 6 hour study visit
measure: Change in hemoglobin concentration
timeFrame: Continuous over 6 hour study visit
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Nydia Chien
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
References: