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

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ClinicalTrials.gov Identifier: NCT02980068
Recruitment Status : Recruiting
First Posted : December 2, 2016
Last Update Posted : April 28, 2021
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Alison Morris, University of Pittsburgh

Study Description
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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.

Condition or disease Intervention/treatment Phase
Pulmonary; Hypertension Heart Failure Preserved Ejection Fraction Drug: 15N Nitrate Drug: 14N Nitrate Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 28, 2017
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 15N Nitrate
single 1,000mg dose of 15N nitrate with 3g of conjugated linoleic acid (CLA).
 Drug: 15N Nitrate
1,000 mg/11.8 mmol, oral, on day one, hour zero
Other Name: 15N Sodium Nitrate
Experimental: 14N Sodium Nitrate
single 1,000mg dose of 14N sodium nitrate with 3g of conjugated linoleic acid (CLA)
 Drug: 14N Nitrate
1,000 mg/11.18 mmol, oral, on day hour, hour zero
Other Name: 14N Sodium Nitrate


Outcome Measures
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Primary Outcome Measures :
  1. Change in nitrate level in urine [ Time Frame: Urine collected approx 0 & 6 hours after drug administration ]
    The investigators will examine urine nitrate

  2. Change in nitrate level in plasma [ Time Frame: Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration ]
    The investigators will examine plasma nitrate

  3. Bacterial content of gut microbiome [ Time Frame: Stool collected before drug administration ]
    Stool will be analyzed for bacterial makeup

  4. Bacterial content of the oral microbiome [ Time Frame: Saliva and tongue scraping will occur preceding administration of drug ]
    Saliva and tongue scraping will be analyzed for bacterial makeup

  5. Change in nitrite level in urine [ Time Frame: Urine collected approx 0 & 6 hours after drug administration ]
    The investigators will examine urine nitrite

  6. Change in nitrite level in plasma [ Time Frame: Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration ]
    The investigators will examine plasma nitrite


Secondary Outcome Measures :
  1. Change in blood pressure [ Time Frame: Frequently over 6 hour study visit ]
  2. Change in heart rate [ Time Frame: Continuous over 6 hour study visit ]
  3. Change in respiratory rate [ Time Frame: Continuous over 6 hour study visit ]
  4. Change in hemoglobin concentration [ Time Frame: Continuous over 6 hour study visit ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 5 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02980068


Contacts
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Contact: Nydia Chien, MSN, RN 412-647-2791 chienn@upmc.edu

Locations
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United States, Pennsylvania
Nydia Chien Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Nydia Chien, MSN, RN    412-647-2791    chienn@upmc.edu   
Principal Investigator: Alison Morris, MD, MS         
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Alison Morris, MD    412-624-8330    morrisa@upmc.edu   
Sponsors and Collaborators
Gladwin, Mark, MD
National Heart, Lung, and Blood Institute (NHLBI)
More Information
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Responsible Party: Alison Morris, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02980068    
Other Study ID Numbers: STUDY19120066
5P01HL103455 ( U.S. NIH Grant/Contract )
First Posted: December 2, 2016    Key Record Dates
Last Update Posted: April 28, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After de-identification, all participant data collected during the trial will be made available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data will be made following publication.
Access Criteria: Data will be available publicly.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Hypertension
Heart Failure
Vascular Diseases
 Cardiovascular Diseases
Heart Diseases
Lung Diseases
Respiratory Tract Diseases