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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Yes
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02980068
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Gladwin, Mark, MD
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH
Overall Status Active, not recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Pulmonary; Hypertension, Heart Failure, Preserved Ejection Fraction
Additional Details

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.

Arms & Interventions

Arms

Experimental: 15N Nitrate

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

Experimental: 14N Sodium Nitrate

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

Interventions

Drug: - 15N Nitrate

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

Drug: - 14N Nitrate

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Nydia Chien, Pittsburgh, Pennsylvania

Status

Address

Nydia Chien

Pittsburgh, Pennsylvania, 15213

University of Pittsburgh, Pittsburgh, Pennsylvania

Status

Address

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213

For more information, please contact PHA at Research@PHAssociation.org and refer to the terms of service below.

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