Chlorhexidine Mouthwash and Oral Nitrate in Adults With Pulmonary Hypertension

This is an open-label, single-center study to examine distinguishing features of the
structure and function of the oral and gut microbiome in volunteers with PH in the breakdown
of oral nitrate and effect on hemodynamics.

The investigators will enroll 40 PH patients over three years. Participants will receive a
single dose of the study drug,:14N Sodium Nitrate(1000mg): standard sodium nitrate, and all
will receive one dose of CLA 3g. CLA will be obtained from GNC (General Nutrition
Corporation) and given once. Participants will be randomized to receive chlorhexidine
gluconate 0.12% (15mL) or placebo to rinse their mouth with for 1 minute.

Oral and gut samples will be collected pre- and post-chlorhexidine treatments. Right heart
catheterization will be performed for research purposes. Catheterization will generally be
performed via the right internal jugular vein access with the assistance of fluoroscopy, if
needed. Once the pulmonary arterial (PA) catheter has been placed in proper position,
measured values will be obtained. The investigators often perform simultaneous measurement of
right atrial pressure and distal pressure (PAP/PAWP) using two transducers in order to assess
both pressures during vasodilator challenge, or other confrontational testing. An initial
hemodynamic profile will be obtained.

With the right heart catheter still in place, participants will be randomized to either
chlorhexidine mouthwash or placebo, then after 30 minutes, all will receive 14N oral nitrate
and CLA. A repeat hemodynamic profile will be performed after two hours. Nitrate metabolites
in plasma will be measured at time 0, 2, and 6 hrs after 14N nitrate dose. Urine nitrite and
nitrate will be measured at 0 and 6 hours. Participants will be monitored with continuous
pulse oximetry and EKG monitoring. Blood pressure measurements will be performed every 15
minutes during the catheterization. Pressure-volume loop and impedance analysis will be
performed at the time of the right heart catheterization (RHC) using the micromanometer
catheter technique to simultaneously measure RV pressure and pulmonary blood flow.
Participants will be monitored in the cardiac catheterization lab after the procedures as per
protocol.

Inclusion Criteria:

- Male or female, 18 years of age or older

- Undergoing clinical right heart catheterization or had a RHC in past 24 months.

- Pulmonary Hypertension: hemodynamically defined by a mean PAP ≥ 25 mm Hg, a PVR > 3
Woods units and normal cardiac index (>2.0 L/min/m2)

- Ability to provide written informed consent

Exclusion Criteria:

- 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

- 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)

- 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 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