Pulmonary HypertensionPhase 1NCT03787082
Chlorhexidine Mouthwash and Oral Nitrate in Adults With Pulmonary Hypertension
A Phase 1 study testing Nitrates and Chlorhexidine Gluconate Mouthwash in people with Pulmonary Hypertension and Heart Failure With Normal Ejection Fraction, run by Gladwin, Mark, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Hypertension, Heart Failure With Normal Ejection Fraction, Pulmonary Heart Disease and Diseases of Pulmonary Circulation
- What is being tested?
- Nitrates and Chlorhexidine Gluconate Mouthwash
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2022to Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Trial of 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.
Read the 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
- Being tested
- Nitrates, Chlorhexidine Gluconate Mouthwash, Placebo Mouthwash
- Medical subject headings
- Hypertension, Pulmonary, Pulmonary Heart Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NitratesDrug
Also called 14N Sodium Nitrate
1,000 mg/11.18 mmol, oral
Chlorhexidine Gluconate MouthwashDrug
Also called Chlorhexidine mouthwash
chlorhexidine gluconate 0.12% (15mL) mouth rinse for 1 minute
Placebo MouthwashDrug
Also called Sterile Water
sterile water (15mL) mouth rinse for 1 minute
| Study group | Role | What they receive |
|---|---|---|
| Chlorhexidine Gluconate Mouthwash | Experimental | rinse with chlorhexidine gluconate 0.12% (15mL) mouthwash before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral Receives: Drug: Nitrates; Drug: Chlorhexidine Gluconate Mouthwash |
| Placebo Mouthwash | Placebo comparator | rinse with placebo mouthwash (15mL) before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral Receives: Drug: Nitrates; Drug: Placebo Mouthwash |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Plasma Nitrate
Measured: At baseline and 2 hours post drug administration
Change in Urine Nitrate
Measured: At baseline and 2 hours post drug administration
Change in Plasma Nitrate
Measured: At baseline and 6 hours post drug administration
Change in Urine Nitrate
Measured: At baseline and 6 hours post drug administration
Change in Plasma Nitrate
Measured: At 2 hours post drug administration and 6 hours post drug administration
Change in Urine Nitrate
Measured: At 2 hours post drug administration and 6 hours post drug administration
Secondary outcomes (1)
Change in Pulmonary Vascular Resistance (PVR)
Measured: At baseline and 2 hours post drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2018
- Study startDec 2022 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Why it stopped: Study was never able to start after the pandemic restrictions lifted
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gladwin, Mark, MD
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), University of Pittsburgh
- Responsible party
- Principal investigator, Alison Morris, University of Pittsburgh
- Investigators
- Alison Morris, MD, MS, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03787082
- Sponsor's protocol ID
- STUDY19120104
- Other IDs
- 5P01HL103455
- Status last verified
- Jul 2022
- First submitted
- 24 Dec 2018
- Last updated
- 7 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: After de-identification, all participant data collected during the trial will be made available.
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Chlorhexidine Mouthwash and Oral Nitrate in Adults With Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT03787082
- Acronym / sponsor ID
- STUDY19120104
- Conditions
- Pulmonary Hypertension, Heart Failure With Normal Ejection Fraction, Pulmonary Heart Disease and Diseases of Pulmonary Circulation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was never able to start after the pandemic restrictions lifted
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Gladwin, Mark, MD
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), University of Pittsburgh
- Study start
- Dec 2022 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 26 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chlorhexidine Gluconate Mouthwash | Experimental | Drug: Nitrates, Drug: Chlorhexidine Gluconate Mouthwashrinse with chlorhexidine gluconate 0.12% (15mL) mouthwash before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral |
| Placebo Mouthwash | Placebo comparator | Drug: Nitrates, Drug: Placebo Mouthwashrinse with placebo mouthwash (15mL) before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NitratesAlso: 14N Sodium Nitrate1,000 mg/11.18 mmol, oral | Drug | Chlorhexidine Gluconate Mouthwash, Placebo Mouthwash |
| Chlorhexidine Gluconate MouthwashAlso: Chlorhexidine mouthwashchlorhexidine gluconate 0.12% (15mL) mouth rinse for 1 minute | Drug | Chlorhexidine Gluconate Mouthwash |
| Placebo MouthwashAlso: Sterile Watersterile water (15mL) mouth rinse for 1 minute | Drug | Placebo Mouthwash |
Primary outcome
Change in Plasma Nitrate
Time frame: At baseline and 2 hours post drug administration
Change in Urine Nitrate
Time frame: At baseline and 2 hours post drug administration
Change in Plasma Nitrate
Time frame: At baseline and 6 hours post drug administration
Change in Urine Nitrate
Time frame: At baseline and 6 hours post drug administration
Change in Plasma Nitrate
Time frame: At 2 hours post drug administration and 6 hours post drug administration
Change in Urine Nitrate
Time frame: At 2 hours post drug administration and 6 hours post drug administration
1 secondary outcome
Change in Pulmonary Vascular Resistance (PVR)
Time frame: At baseline and 2 hours post drug administration
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2022.
- Individual participant dataSharing planned: Yes. After de-identification, all participant data collected during the trial will be made available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alison Morris, MD, MS principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nitrates and Chlorhexidine Gluconate Mouthwash in people with Pulmonary Hypertension and Heart Failure With Normal Ejection Fraction, run by Gladwin, Mark, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 7 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Plasma Nitrate (time frame: At baseline and 2 hours post drug administration). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2022.