Chlorhexidine Mouthwash and Oral Nitrate in Adults With Pulmonary Hypertension

NCT ID: NCT03787082

Last Updated: 2022-07-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-31
• Study Completion Date: 2023-12-31

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.

Participants for whom the RHC done in the study is considered a clinical RHC will be participants who do have an additional follow up RHC scheduled.

Participants for whom the RHC done in the study is considered a research RHC will be those who do not have an additional follow RHC scheduled or who are considered healthy and have not had an RHC before.

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.

Conditions

Pulmonary Hypertension; Heart Failure With Normal Ejection Fraction; Pulmonary Heart Disease and Diseases of Pulmonary Circulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Chlorhexidine Gluconate Mouthwash

rinse with chlorhexidine gluconate 0.12% (15mL) mouthwash before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral

Group Type: EXPERIMENTAL

Nitrates

Intervention Type: DRUG

1,000 mg/11.18 mmol, oral

Chlorhexidine Gluconate Mouthwash

Intervention Type: DRUG

chlorhexidine gluconate 0.12% (15mL) mouth rinse for 1 minute

Placebo Mouthwash

rinse with placebo mouthwash (15mL) before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral

Group Type: PLACEBO_COMPARATOR

Nitrates

Intervention Type: DRUG

1,000 mg/11.18 mmol, oral

Placebo Mouthwash

Intervention Type: DRUG

sterile water (15mL) mouth rinse for 1 minute

Interventions

Nitrates

1,000 mg/11.18 mmol, oral

Intervention Type: DRUG

Chlorhexidine Gluconate Mouthwash

chlorhexidine gluconate 0.12% (15mL) mouth rinse for 1 minute

Intervention Type: DRUG

Placebo Mouthwash

sterile water (15mL) mouth rinse for 1 minute

Intervention Type: DRUG

Other Intervention Names

14N Sodium Nitrate; Chlorhexidine mouthwash; Sterile Water

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Gladwin, Mark, MD

INDIV

Sponsor Role: lead

Responsible Party

Alison Morris

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alison Morris, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Cathy Kessinger

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

5P01HL103455

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY19120104

Identifier Type: -

Identifier Source: org_study_id