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.
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
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
77
1,000 mg/11.8 mmol, oral, on day one, hour zero
1,000 mg/11.18 mmol, oral, on day hour, hour zero
Nydia Chien
Pittsburgh, Pennsylvania, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Change in nitrate level in urine
The investigators will examine urine nitrate
Time frame: Urine collected approx 0 & 6 hours after drug administration
Change in nitrate level in plasma
The investigators will examine plasma nitrate
Time frame: Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration
Bacterial content of gut microbiome
Stool will be analyzed for bacterial makeup
Time frame: Stool collected before drug administration
Bacterial content of the oral microbiome
Saliva and tongue scraping will be analyzed for bacterial makeup
Time frame: Saliva and tongue scraping will occur preceding administration of drug
Change in nitrite level in urine
The investigators will examine urine nitrite
Time frame: Urine collected approx 0 & 6 hours after drug administration
Change in nitrite level in plasma
The investigators will examine plasma nitrite
Time frame: Approx 50cc of blood drawn approx 0, 2, & 6 hours after drug administration
Change in blood pressure
Time frame: Frequently over 6 hour study visit
Change in heart rate
Time frame: Continuous over 6 hour study visit
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Change in respiratory rate
Time frame: Continuous over 6 hour study visit
Change in hemoglobin concentration
Time frame: Continuous over 6 hour study visit