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

NCT ID: NCT02980068

Last Updated: 2022-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-28
• Study Completion Date: 2022-02-25

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.

Conditions

Preserved Ejection Fraction; Pulmonary; Hypertension; Heart Failure

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

15N Nitrate

single 1,000mg dose of 15N nitrate with 3g of conjugated linoleic acid (CLA).

Group Type: EXPERIMENTAL

15N Nitrate

Intervention Type: DRUG

1,000 mg/11.8 mmol, oral, on day one, hour zero

14N Sodium Nitrate

single 1,000mg dose of 14N sodium nitrate with 3g of conjugated linoleic acid (CLA)

Group Type: EXPERIMENTAL

14N Nitrate

Intervention Type: DRUG

1,000 mg/11.18 mmol, oral, on day hour, hour zero

Interventions

15N Nitrate

1,000 mg/11.8 mmol, oral, on day one, hour zero

Intervention Type: DRUG

14N Nitrate

1,000 mg/11.18 mmol, oral, on day hour, hour zero

Intervention Type: DRUG

Other Intervention Names

15N Sodium Nitrate; 14N Sodium Nitrate

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Gladwin, Mark, MD

INDIV

Sponsor Role: lead

Responsible Party

Alison Morris

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Nydia Chien

Pittsburgh, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

5P01HL103455

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY19120066

Identifier Type: -

Identifier Source: org_study_id