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

Heart Failure Clinical Trial

— PMED  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02980068
• Other study ID #: STUDY19120066
• Secondary ID: 5P01HL103455
• Status: Completed
• Phase: Phase 1
• Start date: August 28, 2017
• Est. completion date: February 25, 2022

Study information

• Verified date: March 2022
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: February 25, 2022
• Est. primary completion date: February 25, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Hypertension
• Hypertension, Pulmonary
• Preserved Ejection Fraction
• Pulmonary; Hypertension

Intervention

Drug:
• 15N Nitrate
1,000 mg/11.8 mmol, oral, on day one, hour zero
• 14N Nitrate
1,000 mg/11.18 mmol, oral, on day hour, hour zero

Locations

Country	Name	City	State
United States	Nydia Chien	Pittsburgh	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Gladwin, Mark, MD	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in nitrate level in urine	The investigators will examine urine nitrate	Urine collected approx 0 & 6 hours after drug administration
Primary	Change in nitrate level in plasma	The investigators will examine plasma nitrate	Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration
Primary	Bacterial content of gut microbiome	Stool will be analyzed for bacterial makeup	Stool collected before drug administration
Primary	Bacterial content of the oral microbiome	Saliva and tongue scraping will be analyzed for bacterial makeup	Saliva and tongue scraping will occur preceding administration of drug
Primary	Change in nitrite level in urine	The investigators will examine urine nitrite	Urine collected approx 0 & 6 hours after drug administration
Primary	Change in nitrite level in plasma	The investigators will examine plasma nitrite	Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration
Secondary	Change in blood pressure		Frequently over 6 hour study visit
Secondary	Change in heart rate		Continuous over 6 hour study visit
Secondary	Change in respiratory rate		Continuous over 6 hour study visit
Secondary	Change in hemoglobin concentration		Continuous over 6 hour study visit