A Randomized Trial of Chlorhexidine Mouthwash and Oral Nitrate in Adults With Pulmonary Hypertension
Trial Snapshot
- Phase
- Phase 1
- Status
- Withdrawn
- Sponsor
- Locations
- 1
- Primary Endpoint
- Change in Urine Nitrate
Study Overview
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 volunteers with PH in the breakdown of oral nitrate and effect on hemodynamics.
Detailed Description
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. 5 healthy participants will be enrolled as controls. 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 samples will be collected pre- and post-chlorhexidine treatments and stool samples will be collected post-chlorhexidine treatment.
Right heart catheterization will be performed for clinical or research purposes.
The RHC done (in the last 5 years) that establishes inclusion is not the same RHC done as part of the study in most cases. If there is a strong suspicion of PH based on echocardiography in a patient who has not had a clinical RHC, the first hemodynamic measurements obtained in the clinical RHC will establish inclusion and the RHC study procedures will be performed following confirmation of inclusion.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Masking Description
Participants will receive open label nitrate and be randomly assigned to either chlorhexidine mouthwash or placebo mouthwash. The participant and investigator will be blinded to which mouthwash the participant is randomized.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Male or female, 18 years of age or older
- •Undergoing clinical right heart catheterization or had a RHC in past 5 years if in PH group
- •Pulmonary Hypertension: hemodynamically defined by a mean PAP ≥ 25 mm Hg and have a PVR > 3 Woods units and normal cardiac index (>2.0 L/min/m2)
- •Healthy Control group: no history of or active cardiac or pulmonary disease
- •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
- •Has chronic renal insufficiency as defined by serum creatinine >3 mg/dL in the last 6 months or requiring dialytic support as reported in the medical record
- •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
Arms & Interventions
Chlorhexidine Gluconate Mouthwash
rinse with chlorhexidine gluconate 0.12% (15mL) mouthwash before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral
Intervention: Chlorhexidine Gluconate Mouthwash (Drug)
Placebo Mouthwash
rinse with placebo mouthwash (15mL) before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral
Intervention: Placebo Mouthwash (Drug)
Placebo Mouthwash
rinse with placebo mouthwash (15mL) before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral
Intervention: Nitrates (Drug)
Chlorhexidine Gluconate Mouthwash
rinse with chlorhexidine gluconate 0.12% (15mL) mouthwash before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral
Intervention: Nitrates (Drug)
Outcomes
Primary Outcomes
Change in Urine Nitrate
Time Frame: At 2 hours post drug administration and 6 hours post drug administration
Change in Plasma Nitrate
Time Frame: At 2 hours post drug administration and 6 hours post drug administration
Secondary Outcomes
- Change in Pulmonary Vascular Resistance (PVR)(At baseline and 2 hours post drug administration)
Investigators
Alison Morris
Professor
University of Pittsburgh