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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 : October 13, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
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: Nitrates Phase 1

Detailed Description:

We will enroll 60 Group II PH (PH-HFpEF) 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 Group II PH 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

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 : July 2020
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

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


Outcome Measures

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 at conclusion of study visit or up to 48 hours after drug administration ]
    Stool will be analyzed for bacterial makeup

  4. 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

  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, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Undergoing clinical right heart catheterization or RHC in the past 6 months.
  • PH-HFpEF group: PH secondary to heart failure with preserved ejection fraction (PH-HFpEF) hemodynamically defined by a mean PAP ≥ 25 mm Hg, a PCWP > 15 mm Hg, and have a PVR > 3 Woods units and normal cardiac index (>2.0 L/min/m2)
  • Control group: Normal hemodynamics (mean PAP < 25 mm Hg, PCWP ≤ 15 mm Hg) on clinical right heart catheterization within the prior 6 months
  • Ability to provide written informed consent

Exclusion Criteria:

  • Use of systemic antibiotics, chlorhexidine mouthwash, or immune-suppression (oral prednisone, chemotherapy, etc.) within the previous three months
  • 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
  • History of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication) defined as moderate to severe hepatic impairment (Child-Pugh Class B-C)
  • Has chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL at screening or requires dialytic support
  • Known history of left ventricular ejection fraction < 45% by multiple gated acquisition scan (MUGA), angiography, or echocardiography
  • History of atrial septostomy
  • Repaired or unrepaired congenital heart disease
  • Pericardial constriction
  • Restrictive or congestive 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

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
Contact: Cathy Kessinger, RN 412-624-8330 kessingercj@pitt.edu
Contact: Cathy Kessinger, RN 412-624-8330 kessingercj@upmc.edu

Locations
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Noel Britton, BS    412-383-5289    brittonm@upmc.edu   
Contact: Cathy Kessinger, RN    412-624-8330    kessingercj@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   
Contact: Cathy kessingercj, RN    4126248330    kessingercj@upmc.edu   
Sponsors and Collaborators
Gladwin, Mark, MD
National Heart, Lung, and Blood Institute (NHLBI)
More Information

Responsible Party: Alison Morris, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02980068     History of Changes
Other Study ID Numbers: PRO16090149
5P01HL103455 ( U.S. NIH Grant/Contract )
First Posted: December 2, 2016    Key Record Dates
Last Update Posted: October 13, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hypertension
Heart Failure
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Lung Diseases
Respiratory Tract Diseases