Back to resultsA Study of Oral Nitrate in Adults With Pulmonary Hypertension With Heart Failure and Preserved Ejection Fraction (PMED)
Primary Purpose
Pulmonary; Hypertension, Heart Failure, Preserved Ejection Fraction
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
15N Nitrate
14N Nitrate
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary; Hypertension
Eligibility 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
Sites / Locations
- Nydia Chien
- University of Pittsburgh
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
15N Nitrate
14N Sodium Nitrate
Arm Description
single 1,000mg dose of 15N nitrate with 3g of conjugated linoleic acid (CLA).
single 1,000mg dose of 14N sodium nitrate with 3g of conjugated linoleic acid (CLA)
Outcomes
Primary Outcome Measures
Change in nitrate level in urine
The investigators will examine urine nitrate
Change in nitrate level in plasma
The investigators will examine plasma nitrate
Bacterial content of gut microbiome
Stool will be analyzed for bacterial makeup
Bacterial content of the oral microbiome
Saliva and tongue scraping will be analyzed for bacterial makeup
Change in nitrite level in urine
The investigators will examine urine nitrite
Change in nitrite level in plasma
The investigators will examine plasma nitrite
Secondary Outcome Measures
Change in blood pressure
Change in heart rate
Change in respiratory rate
Change in hemoglobin concentration
Full Information
NCT ID
NCT02980068
First Posted
November 17, 2016
Last Updated
March 21, 2022
Sponsor
Gladwin, Mark, MD
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT02980068
Brief Title
A Study of Oral Nitrate in Adults With Pulmonary Hypertension With Heart Failure and Preserved Ejection Fraction
Acronym
PMED
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
August 28, 2017 (Actual)
Primary Completion Date
February 25, 2022 (Actual)
Study Completion Date
February 25, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Gladwin, Mark, MD
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary; Hypertension, Heart Failure, Preserved Ejection Fraction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
77 (Actual)
8. Arms, Groups, and Interventions
Arm Title
15N Nitrate
Arm Type
Experimental
Arm Description
single 1,000mg dose of 15N nitrate with 3g of conjugated linoleic acid (CLA).
Arm Title
14N Sodium Nitrate
Arm Type
Experimental
Arm Description
single 1,000mg dose of 14N sodium nitrate with 3g of conjugated linoleic acid (CLA)
Intervention Type
Drug
Intervention Name(s)
15N Nitrate
Other Intervention Name(s)
15N Sodium Nitrate
Intervention Description
1,000 mg/11.8 mmol, oral, on day one, hour zero
Intervention Type
Drug
Intervention Name(s)
14N Nitrate
Other Intervention Name(s)
14N Sodium Nitrate
Intervention Description
1,000 mg/11.18 mmol, oral, on day hour, hour zero
Primary Outcome Measure Information:
Title
Change in nitrate level in urine
Description
The investigators will examine urine nitrate
Time Frame
Urine collected approx 0 & 6 hours after drug administration
Title
Change in nitrate level in plasma
Description
The investigators will examine plasma nitrate
Time Frame
Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration
Title
Bacterial content of gut microbiome
Description
Stool will be analyzed for bacterial makeup
Time Frame
Stool collected before drug administration
Title
Bacterial content of the oral microbiome
Description
Saliva and tongue scraping will be analyzed for bacterial makeup
Time Frame
Saliva and tongue scraping will occur preceding administration of drug
Title
Change in nitrite level in urine
Description
The investigators will examine urine nitrite
Time Frame
Urine collected approx 0 & 6 hours after drug administration
Title
Change in nitrite level in plasma
Description
The investigators will examine plasma nitrite
Time Frame
Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration
Secondary Outcome Measure Information:
Title
Change in blood pressure
Time Frame
Frequently over 6 hour study visit
Title
Change in heart rate
Time Frame
Continuous over 6 hour study visit
Title
Change in respiratory rate
Time Frame
Continuous over 6 hour study visit
Title
Change in hemoglobin concentration
Time Frame
Continuous over 6 hour study visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Facility Information:
Facility Name
Nydia Chien
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
After de-identification, all participant data collected during the trial will be made available.
IPD Sharing Time Frame
Data will be made following publication.
IPD Sharing Access Criteria
Data will be available publicly.
Learn more about this trial
A Study of Oral Nitrate in Adults With Pulmonary Hypertension With Heart Failure and Preserved Ejection Fraction
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