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

NCT02980068 | Completed Phase 1 FDA Drug

• 2 other identifiers: STUDY191200665P01HL103455
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 2

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.

Conditions

Pulmonary; Hypertension; Heart Failure; Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (6)

• Change in nitrate level in urine

  The investigators will examine urine nitrate

  Urine collected approx 0 & 6 hours after drug administration

• 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

• Bacterial content of gut microbiome

  Stool will be analyzed for bacterial makeup

  Stool collected before drug administration

• 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

• Change in nitrite level in urine

  The investigators will examine urine nitrite

  Urine collected approx 0 & 6 hours after drug administration

• 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 Outcomes (4)

• Change in blood pressure

  Frequently over 6 hour study visit

• Change in heart rate

  Continuous over 6 hour study visit

• Change in respiratory rate

  Continuous over 6 hour study visit

• Change in hemoglobin concentration

  Continuous over 6 hour study visit

Study Arms (2)

15N Nitrate

EXPERIMENTAL

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

Drug: 15N Nitrate

14N Sodium Nitrate

EXPERIMENTAL

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

Drug: 14N Nitrate

Interventions

15N Nitrate DRUG

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

Also known as: 15N Sodium Nitrate

15N Nitrate

14N Nitrate DRUG

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

Also known as: 14N Sodium Nitrate

14N Sodium Nitrate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gladwin, Mark, MD: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Nydia Chien

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Heart Failure

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 17, 2016
• First Posted: December 2, 2016
• Study Start: August 28, 2017
• Primary Completion: February 25, 2022
• Study Completion: February 25, 2022
• Last Updated: March 22, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be made following publication.
• Access Criteria: Data will be available publicly.

Locations

US (2)