Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Chlorhexidine Mouthwash and Oral Nitrate in Adults With Pulmonary Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03787082
Recruitment Status : Not yet recruiting
First Posted : December 25, 2018
Last Update Posted : August 21, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Pittsburgh
Information provided by (Responsible Party):
Alison Morris, University of Pittsburgh

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.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Heart Failure With Normal Ejection Fraction Pulmonary Heart Disease and Diseases of Pulmonary Circulation Drug: Nitrates Drug: Chlorhexidine Gluconate Mouthwash Drug: Placebo Mouthwash Phase 1

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Primary Purpose: Treatment
Official Title: A Randomized Trial of Chlorhexidine Mouthwash and Oral Nitrate in Adults With Pulmonary Hypertension
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021


Arm Intervention/treatment
Experimental: Chlorhexidine Gluconate Mouthwash
rinse with chlorhexidine gluconate 0.12% (15mL) mouthwash before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral
Drug: Nitrates
1,000 mg/11.18 mmol, oral
Other Name: 14N Sodium Nitrate

Drug: Chlorhexidine Gluconate Mouthwash
chlorhexidine gluconate 0.12% (15mL) mouth rinse for 1 minute
Other Name: Chlorhexidine mouthwash

Placebo Comparator: Placebo Mouthwash
rinse with placebo mouthwash (15mL) before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral
Drug: Nitrates
1,000 mg/11.18 mmol, oral
Other Name: 14N Sodium Nitrate

Drug: Placebo Mouthwash
sterile water (15mL) mouth rinse for 1 minute
Other Name: Sterile Water




Primary Outcome Measures :
  1. Change in Plasma Nitrate [ Time Frame: At baseline and 2 hours post drug administration ]
  2. Change in Urine Nitrate [ Time Frame: At baseline and 2 hours post drug administration ]
  3. Change in Plasma Nitrate [ Time Frame: At baseline and 6 hours post drug administration ]
  4. Change in Urine Nitrate [ Time Frame: At baseline and 6 hours post drug administration ]
  5. Change in Plasma Nitrate [ Time Frame: At 2 hours post drug administration and 6 hours post drug administration ]
  6. Change in Urine Nitrate [ Time Frame: At 2 hours post drug administration and 6 hours post drug administration ]

Secondary Outcome Measures :
  1. Change in Pulmonary Vascular Resistance (PVR) [ Time Frame: At baseline and 2 hours post drug administration ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03787082


Contacts
Layout table for location contacts
Contact: Noel Britton, MPH 4123835289 brittonrn@upmc.edu
Contact: Cathy Kessinger, RN 412-624-8330 kessingercj@upmc.edu

Locations
Layout table for location information
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Gladwin, Mark, MD
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Pittsburgh
Investigators
Layout table for investigator information
Principal Investigator: Alison Morris, MD, MS University of Pittsburgh

Layout table for additonal information
Responsible Party: Alison Morris, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03787082     History of Changes
Other Study ID Numbers: PRO18080517
5P01HL103455 ( U.S. NIH Grant/Contract )
First Posted: December 25, 2018    Key Record Dates
Last Update Posted: August 21, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After de-identification, all participant data collected during the trial will be made available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data will be made following publication.
Access Criteria: Data will be available publicly.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension, Pulmonary
Hypertension
Heart Failure
Heart Diseases
Pulmonary Heart Disease
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Chlorhexidine
Chlorhexidine gluconate
Anti-Infective Agents, Local
Anti-Infective Agents
Disinfectants
Dermatologic Agents