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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02980068
Recruitment Status : Active, not recruiting
First Posted : December 2, 2016
Last Update Posted : June 4, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Alison Morris, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE November 17, 2016
First Posted Date  ICMJE December 2, 2016
Last Update Posted Date June 4, 2020
Actual Study Start Date  ICMJE August 28, 2017
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 24, 2018)
  • Change in nitrate level in urine [ Time Frame: Urine collected approx 0 & 6 hours after drug administration ]
    The investigators will examine urine nitrate
  • 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
  • Bacterial content of gut microbiome [ Time Frame: Stool collected before drug administration ]
    Stool will be analyzed for bacterial makeup
  • 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
  • Change in nitrite level in urine [ Time Frame: Urine collected approx 0 & 6 hours after drug administration ]
    The investigators will examine urine nitrite
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: December 1, 2016)
  • Change in nitrate level in urine [ Time Frame: Urine collected approx 0 & 6 hours after drug administration ]
    The investigators will examine urine nitrate
  • 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
  • Bacterial content of gut microbiome [ Time Frame: Stool collected at conclusion of study visit or up to 48 hours after drug administration ]
    Stool will be analyzed for bacterial makeup
  • Bacterial content of the oral microbiome [ Time Frame: Tongue scraping will occur immediately preceding administration of drug ]
    Tongue scraping will be analyzed for bacterial makeup
  • Change in nitrite level in urine [ Time Frame: Urine collected approx 0 & 6 hours after drug administration ]
    The investigators will examine urine nitrite
  • 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2016)
  • Change in blood pressure [ Time Frame: Frequently over 6 hour study visit ]
  • Change in heart rate [ Time Frame: Continuous over 6 hour study visit ]
  • Change in respiratory rate [ Time Frame: Continuous over 6 hour study visit ]
  • Change in hemoglobin concentration [ Time Frame: Continuous over 6 hour study visit ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Oral Nitrate in Adults With Pulmonary Hypertension With Heart Failure and Preserved Ejection Fraction
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pulmonary; Hypertension
  • Heart Failure
  • Preserved Ejection Fraction
Intervention  ICMJE
  • Drug: 15N Nitrate
    1,000 mg/11.8 mmol, oral, on day one, hour zero
    Other Name: 15N Sodium Nitrate
  • Drug: 14N Nitrate
    1,000 mg/11.18 mmol, oral, on day hour, hour zero
    Other Name: 14N Sodium Nitrate
Study Arms  ICMJE
  • Experimental: 15N Nitrate
    single 1,000mg dose of 15N nitrate with 3g of conjugated linoleic acid (CLA).
    Intervention: Drug: 15N Nitrate
  • Experimental: 14N Sodium Nitrate
    single 1,000mg dose of 14N sodium nitrate with 3g of conjugated linoleic acid (CLA)
    Intervention: Drug: 14N Nitrate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 1, 2016)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02980068
Other Study ID Numbers  ICMJE STUDY19120066
5P01HL103455 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: Data will be made following publication.
Access Criteria: Data will be available publicly.
Responsible Party Alison Morris, University of Pittsburgh
Study Sponsor  ICMJE Gladwin, Mark, MD
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE Not Provided
PRS Account University of Pittsburgh
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP