Probiotic Effect on Dietary Nitrate to Plasma Nitrite Production ( OPEDNPN )
NCT ID: NCT06375694
Last Updated: 2024-07-19
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
RECRUITING
Clinical Phase
NA
Total Enrollment
20 participants
Study Classification
INTERVENTIONAL
Study Start Date
2024-06-01
Study Completion Date
2025-05-31
Brief Summary
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Nitric Oxide (NO) is an important molecule that is produced naturally in the body and that helps maintain healthy blood flow. Low availability of NO contributes to many diseases while administration of NO is therapeutic.
In addition to being made naturally in the body, NO can be obtained through the diet via the Nitrate-Nitrite-NO cycle. Nitrate, which is abundant in green leafy vegetables and beetroot juice, is partially converted to nitrite by oral bacteria. The nitrate and nitrite are taken up into the blood and nitrite is converted into NO. Remaining nitrate in the blood is taken back up into the mouth by salivary glands and the cycle continues. Emerging studies suggest that the Nitrate-Nitrite-NO cycle may contribute to cardiovascular health. In addition, there have been many studies where dietary nitrate is given to increase NO and treat various conditions.
The current study rests on the premise that the quality of the oral microbiome plays a major role in the Nitrate-Nitrite-NO cycle and hence cardiovascular health and the efficacy of dietary nitrate interventions. Investigators have begun to identify oral bacterial species that are effective nitrite producers as well as though that are nitrite depleters (those that interfere with nitrite production from nitrate).
In laboratory experiments, certain bacterial species have been shown to block nitrate to nitrite conversion by other oral bacteria. These nitrite depleting species are found in a commercially available oral probiotic designed to improve oral health. The purpose of this study is to examine if use of the probiotic negatively affects the Nitrate-Nitrite-NO cycle. Nitrate to Nitrite conversion will be assessed by measuring plasma levels of nitrite before and after consumption of nitrate-rich beetroot juice. Dietary nitrate to plasma nitrite conversion will assessed at baseline and after one week of consumption of the probiotic or a placebo (follow-up). The primary hypothesis of this study is that participants that consume the probiotic will have lower nitrate to nitrite conversion at follow-up compared to baseline and that there will be no significant change in nitrate to nitrite conversion between baseline and follow-up for participants who consume the placebo.
While this study does not aim to treat any specific disease, it is intended to elucidate a basic physiological function that may be relevant to cardiovascular health and certain NO-based therapeutics.
In addition to being made naturally in the body, NO can be obtained through the diet via the Nitrate-Nitrite-NO cycle. Nitrate, which is abundant in green leafy vegetables and beetroot juice, is partially converted to nitrite by oral bacteria. The nitrate and nitrite are taken up into the blood and nitrite is converted into NO. Remaining nitrate in the blood is taken back up into the mouth by salivary glands and the cycle continues. Emerging studies suggest that the Nitrate-Nitrite-NO cycle may contribute to cardiovascular health. In addition, there have been many studies where dietary nitrate is given to increase NO and treat various conditions.
The current study rests on the premise that the quality of the oral microbiome plays a major role in the Nitrate-Nitrite-NO cycle and hence cardiovascular health and the efficacy of dietary nitrate interventions. Investigators have begun to identify oral bacterial species that are effective nitrite producers as well as though that are nitrite depleters (those that interfere with nitrite production from nitrate).
In laboratory experiments, certain bacterial species have been shown to block nitrate to nitrite conversion by other oral bacteria. These nitrite depleting species are found in a commercially available oral probiotic designed to improve oral health. The purpose of this study is to examine if use of the probiotic negatively affects the Nitrate-Nitrite-NO cycle. Nitrate to Nitrite conversion will be assessed by measuring plasma levels of nitrite before and after consumption of nitrate-rich beetroot juice. Dietary nitrate to plasma nitrite conversion will assessed at baseline and after one week of consumption of the probiotic or a placebo (follow-up). The primary hypothesis of this study is that participants that consume the probiotic will have lower nitrate to nitrite conversion at follow-up compared to baseline and that there will be no significant change in nitrate to nitrite conversion between baseline and follow-up for participants who consume the placebo.
While this study does not aim to treat any specific disease, it is intended to elucidate a basic physiological function that may be relevant to cardiovascular health and certain NO-based therapeutics.
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Detailed Description
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Background
Nitric oxide (NO) plays critical roles in a myriad of cellular and molecular mechanisms regulating physiology and function of various organs and systems.1,2 Low NO bioavailability contributes to pathology in multiple diseases including hemolytic anemias,3 malaria,4,5 transfusion of older stored blood,6,7 chronic heart failure,8 atherosclerosis,9 and diabetes.10 Recent reports suggest that the oral microbiome is linked with regulating NO homeostasis through the action of certain bacteria that have an ability to reduce nitrate to nitrite.11-15 Nitrite is then further reduced to NO through a variety of mechanisms in different tissues.16,17 Plasma nitrate is taken up back into the oral cavity by salivary glands so that the nitrate-nitrite-NO cycle provides sustained increases in NO bioavailability. Many clinical studies have used dietary nitrate as a source of NO through nitrite conversion.18-24 However, there is substantial variability in the clinical outcomes due to dietary nitrate intake and this is reflected in variability in the amount of nitrate converted to plasma nitrite.13,24-29 30. The variability and hence a large overall limitation in efficacy of dietary nitrate based treatments has been attributed to the capacity of the oral microbiome to reduce nitrate to nitrite.24-27 Preliminary work has begun to identify bacterial strains that are efficient nitrate to nitrite converters as well as those that actually inhibit nitrate to nitrite conversion.31,32 The efficiency of the nitrate-nitrite-NO cycle and the role of oral bacteria may contribute to normal health.11 Thus, understanding the variability in nitrate to nitrite conversion and aspects of the oral microbiome could lead to improvements in normal cardiovascular health. In addition, in order to maximize benefits from dietary nitrate interventions, we need to understand factors of the oral microbiome that affect nitrate to nitrite conversion. The investigators have recently discovered that several species of Lactobacillus produce a metabolite that blunts nitrate to nitrite conversion by other oral bacteria in vitro. Several of these Lactobacillus species are the main component of a commercially available oral probiotic, https://www.amazon.com/Dental-Probiotics-Breath-Gingivitis-Throat/dp/B096SZSFFS
Purpose
The purpose of this study is to determine if Lactobacillus will blunt dietary nitrate to plasma nitrite conversion.
The investigators hypothesize that the presence of oral Lactobacillus will blunt the conversion of dietary nitrate to plasma nitrite and will test this by comparing the conversion before and after use of this probiotic.
The main hypothesis rests on the auxiliary hypothesis that use of the oral probiotic will results in increased abundance of Lactobacillus in the oral cavity and will test this through genomic sequencing.
Methods OPEDNPN All eligible volunteers will be consented after learning about the study and agreeing to participate. Volunteers will be randomly assigned to one of two groups: (1) Probiotic and (2) Placebo. A total of 20 volunteers (10 per group) will participate in the study. The only difference for participants for each group will be whether they receive the placebo or probiotic.
All volunteers will participate in two visits: (1) Visit 1, baseline and (2) Visit 2, follow up. At each visit, volunteers will report to the Olin Physical Lab room 208 after having fasted for 3 hours prior. They can drink water one hour before the visit. Participants will be instructed not to use anti-bacterial mouthwash the day of the visit. The participant will be asked to provide 4 mL of saliva and a study team member will collect a bacterial sample from the posterior dorsal surface of their tongue (as described below). These samples will be frozen at -80 degrees for genetic analysis and identification of bacterial strains.
After saliva and tongue samples are collected, blood will be drawn (as described below) for plasma nitrite and nitrate determination. This blood sample will be the "pre-" sample collected at baseline and follow-up. Volunteers will then drink one 70 mL Beet it Sport Nitrate 400 shot (https://www.beet-it.us/pages/beet-it-sports). A "post-" blood draw will be collected 2.5 hours after consumption of the beetroot juice.
At Visit 1, after the second blood draw, volunteers will receive 7 days worth of either probiotic or the placebo. Volunteers will consume the probiotic (or placebo) as indicated by the manufacturer of the probiotic once a day. On day 8, the volunteers will return for visit 2.
The data will include (1) baseline and follow-up analysis of oral bacterial strains and (2) Pre- and post-beet juice consumption plasma nitrite and nitrate levels. The investigators hypothesize that the abundance of Lactobacillus will be higher at follow-up compared to baseline for volunteers taking the probiotic but that there will be no change in the placebo group. The investigators also hypothesize that the change in plasma nitrite (post minus pre) will be lower at follow-up than at baseline for volunteers taking the probiotic but that there will be no change in the placebo group.
* Study Materials (all commercially available):
1. Placebo: Honest Placebo Pills by Zeebo
2. Herbiotics Oral + Ent Probiotic
3. Beet it Sport Nitrate 400 shot
* Collection of Saliva and Tongue scraping. Volunteers will report to the Olin Physical Lab room 208 after having fasted for 3 hours prior. They can drink water one hour before the visit. Participants will be instructed not to use anti-bacterial mouthwash the day of the visit. The participant will be asked to provide 4 mL of saliva by spitting into a microcentrifuge tube. For the tongue samples, a HydraFlock 6" Sterile Large Flock Swab w/Polystyrene Handle (Puritan Medical) will be used to collect scrapings. Volunteers will be asked to open their mouths as wide as possible and stick out their tongue. The posterior 1/3 of the dorsal surface of the tongue will be sampled by scraping lightly to moderately firmly the dorsal surface of the tongue back and forth Scraping will take a minute or so. The tongue scraping will be placed in 0.85 mL of buffered sterile saline and 0.15 mL glycerol. All samples will be frozen at -80°C and sent to Professor Hariom Yadav at the University of South Florida for genomic analysis.
* Blood draws and processing Blood will be drawn by a certified, trained phlebotomist. Blood samples (maximum \~10 mL) will be collected from participants following consent. Blood will be collected at each visit pre and 2.5 hours post beet juice consumption. Blood will be drawn as close to the 2.5 hour mark as possible. Realistically, it may occur between 2 to 3 hours after the final study beverage is consumed. Blood will be drawn by lab personnel with certified phlebotomy training via standard venipuncture methods or Tasso HemolinkTM device. The HemoLinkTM is an FDA-approved blood collection device that uses small lancets and gentle suction to collect a very small sample (\~ ¼ teaspoons) of blood. Blood will be collected in standard blood collection tubes (e.g. citrate (blue-top), EDTA (purple-top) and heparin (green-top)) and labeled appropriately. The preferred tube is a 4 mL heparin tube. All blood samples drawn for research purposes will be identified by the study participant number and date/time of collection, which will also be recorded on the standardized data collection form. No personal identifying information will be included on the samples processed for research purposes. All blood samples will be immediately spun immediately in a centrifuge at 600-800g for five minutes and the supernatant collected. The plasma will be frozen on dry ice and then stored at -80°C for analysis of nitrite and nitrate content.
* Probiotic or placebo consumption Both the probiotic and placebo will be consumed twice a day according to instructions for the probiotic. One capsule is chewed or allowed to melt in the volunteer's mouth and then the contents are switched around in the mouth before being swallowed.
Risks Approximately 10 mL of blood will be drawn from patients willing to participate. This will be done in the usual fashion, preparing the venipuncture site with the local anesthetic EMLA, then drawing blood through a small gauge (23 or 21) butterfly needle. Drawing blood from a vein may be associated with discomfort or bruising at the site of needle puncture. Rarely, fainting or infection at the site of needle puncture may occur. All blood will be drawn from a person trained in phlebotomy. There will be no way to trace the blood back to the donor.
There are no known health risks for donating saliva or tongue scrapings from individuals who will be included in the study. There is a very minimal risk of linking individuals to the study. There will be no way to trace the saliva or tongue scrapings back to the donor.
Protections Against Risk Strategies for protection against risk. To protect privacy of participants and confidentiality of research data, no personal information regarding individual participants will be linked to the in vitro studies.
Plans for medical attention. In case of injury (which is extremely unlikely) as a result of saliva donation, the individuals will be instructed to contact their physician and medical care will be offered and charged to available research coverage maintained at Wake Forest School of Medicine.
In case of injury as a result of blood drawing, the patients will be instructed to contact their physician and medical care will be offered and charged to available research coverage maintained at Wake Forest School of Medicine. Blood drawn on the Reynolda campus is not a clinical setting, but blood will be drawn by trained phlebotomists with years of experience who maintain their training.
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes will be promptly reported by the principal investigator or designated member of the research team to the IRB and sponsor or appropriate government agency if appropriate.
Incidental Findings. No incidental findings are expected to be discovered in this study as measures of bacterial nitrate reduction are not currently of clinical relevance so a strange, individual result in that measure would not be worth communicating.
Sample size assessment and statistical analysis
The investigators plan to enroll 10 participants who receive the probiotic and 10 participants who receive the placebo. The investigators hypothesize that, using a paired t-test, participants taking the probiotic will have significantly (P \< .05) lower change in plasma nitrite (post minus pre) at follow up compared to baseline while there will be no significant effect of the placebo (paired t-test).
The Investigators calculated that they would have 80% power to measure a 75% decrease in the change in nitrite at follow-up compared to baseline for the probiotic group with 10 participants per group (Continuous endpoint Two independent samples). The investigators assumed a 60% standard deviation in the change in nitrite for follow-up vs baseline based on previous data from our lab.
Nitric oxide (NO) plays critical roles in a myriad of cellular and molecular mechanisms regulating physiology and function of various organs and systems.1,2 Low NO bioavailability contributes to pathology in multiple diseases including hemolytic anemias,3 malaria,4,5 transfusion of older stored blood,6,7 chronic heart failure,8 atherosclerosis,9 and diabetes.10 Recent reports suggest that the oral microbiome is linked with regulating NO homeostasis through the action of certain bacteria that have an ability to reduce nitrate to nitrite.11-15 Nitrite is then further reduced to NO through a variety of mechanisms in different tissues.16,17 Plasma nitrate is taken up back into the oral cavity by salivary glands so that the nitrate-nitrite-NO cycle provides sustained increases in NO bioavailability. Many clinical studies have used dietary nitrate as a source of NO through nitrite conversion.18-24 However, there is substantial variability in the clinical outcomes due to dietary nitrate intake and this is reflected in variability in the amount of nitrate converted to plasma nitrite.13,24-29 30. The variability and hence a large overall limitation in efficacy of dietary nitrate based treatments has been attributed to the capacity of the oral microbiome to reduce nitrate to nitrite.24-27 Preliminary work has begun to identify bacterial strains that are efficient nitrate to nitrite converters as well as those that actually inhibit nitrate to nitrite conversion.31,32 The efficiency of the nitrate-nitrite-NO cycle and the role of oral bacteria may contribute to normal health.11 Thus, understanding the variability in nitrate to nitrite conversion and aspects of the oral microbiome could lead to improvements in normal cardiovascular health. In addition, in order to maximize benefits from dietary nitrate interventions, we need to understand factors of the oral microbiome that affect nitrate to nitrite conversion. The investigators have recently discovered that several species of Lactobacillus produce a metabolite that blunts nitrate to nitrite conversion by other oral bacteria in vitro. Several of these Lactobacillus species are the main component of a commercially available oral probiotic, https://www.amazon.com/Dental-Probiotics-Breath-Gingivitis-Throat/dp/B096SZSFFS
Purpose
The purpose of this study is to determine if Lactobacillus will blunt dietary nitrate to plasma nitrite conversion.
The investigators hypothesize that the presence of oral Lactobacillus will blunt the conversion of dietary nitrate to plasma nitrite and will test this by comparing the conversion before and after use of this probiotic.
The main hypothesis rests on the auxiliary hypothesis that use of the oral probiotic will results in increased abundance of Lactobacillus in the oral cavity and will test this through genomic sequencing.
Methods OPEDNPN All eligible volunteers will be consented after learning about the study and agreeing to participate. Volunteers will be randomly assigned to one of two groups: (1) Probiotic and (2) Placebo. A total of 20 volunteers (10 per group) will participate in the study. The only difference for participants for each group will be whether they receive the placebo or probiotic.
All volunteers will participate in two visits: (1) Visit 1, baseline and (2) Visit 2, follow up. At each visit, volunteers will report to the Olin Physical Lab room 208 after having fasted for 3 hours prior. They can drink water one hour before the visit. Participants will be instructed not to use anti-bacterial mouthwash the day of the visit. The participant will be asked to provide 4 mL of saliva and a study team member will collect a bacterial sample from the posterior dorsal surface of their tongue (as described below). These samples will be frozen at -80 degrees for genetic analysis and identification of bacterial strains.
After saliva and tongue samples are collected, blood will be drawn (as described below) for plasma nitrite and nitrate determination. This blood sample will be the "pre-" sample collected at baseline and follow-up. Volunteers will then drink one 70 mL Beet it Sport Nitrate 400 shot (https://www.beet-it.us/pages/beet-it-sports). A "post-" blood draw will be collected 2.5 hours after consumption of the beetroot juice.
At Visit 1, after the second blood draw, volunteers will receive 7 days worth of either probiotic or the placebo. Volunteers will consume the probiotic (or placebo) as indicated by the manufacturer of the probiotic once a day. On day 8, the volunteers will return for visit 2.
The data will include (1) baseline and follow-up analysis of oral bacterial strains and (2) Pre- and post-beet juice consumption plasma nitrite and nitrate levels. The investigators hypothesize that the abundance of Lactobacillus will be higher at follow-up compared to baseline for volunteers taking the probiotic but that there will be no change in the placebo group. The investigators also hypothesize that the change in plasma nitrite (post minus pre) will be lower at follow-up than at baseline for volunteers taking the probiotic but that there will be no change in the placebo group.
* Study Materials (all commercially available):
1. Placebo: Honest Placebo Pills by Zeebo
2. Herbiotics Oral + Ent Probiotic
3. Beet it Sport Nitrate 400 shot
* Collection of Saliva and Tongue scraping. Volunteers will report to the Olin Physical Lab room 208 after having fasted for 3 hours prior. They can drink water one hour before the visit. Participants will be instructed not to use anti-bacterial mouthwash the day of the visit. The participant will be asked to provide 4 mL of saliva by spitting into a microcentrifuge tube. For the tongue samples, a HydraFlock 6" Sterile Large Flock Swab w/Polystyrene Handle (Puritan Medical) will be used to collect scrapings. Volunteers will be asked to open their mouths as wide as possible and stick out their tongue. The posterior 1/3 of the dorsal surface of the tongue will be sampled by scraping lightly to moderately firmly the dorsal surface of the tongue back and forth Scraping will take a minute or so. The tongue scraping will be placed in 0.85 mL of buffered sterile saline and 0.15 mL glycerol. All samples will be frozen at -80°C and sent to Professor Hariom Yadav at the University of South Florida for genomic analysis.
* Blood draws and processing Blood will be drawn by a certified, trained phlebotomist. Blood samples (maximum \~10 mL) will be collected from participants following consent. Blood will be collected at each visit pre and 2.5 hours post beet juice consumption. Blood will be drawn as close to the 2.5 hour mark as possible. Realistically, it may occur between 2 to 3 hours after the final study beverage is consumed. Blood will be drawn by lab personnel with certified phlebotomy training via standard venipuncture methods or Tasso HemolinkTM device. The HemoLinkTM is an FDA-approved blood collection device that uses small lancets and gentle suction to collect a very small sample (\~ ¼ teaspoons) of blood. Blood will be collected in standard blood collection tubes (e.g. citrate (blue-top), EDTA (purple-top) and heparin (green-top)) and labeled appropriately. The preferred tube is a 4 mL heparin tube. All blood samples drawn for research purposes will be identified by the study participant number and date/time of collection, which will also be recorded on the standardized data collection form. No personal identifying information will be included on the samples processed for research purposes. All blood samples will be immediately spun immediately in a centrifuge at 600-800g for five minutes and the supernatant collected. The plasma will be frozen on dry ice and then stored at -80°C for analysis of nitrite and nitrate content.
* Probiotic or placebo consumption Both the probiotic and placebo will be consumed twice a day according to instructions for the probiotic. One capsule is chewed or allowed to melt in the volunteer's mouth and then the contents are switched around in the mouth before being swallowed.
Risks Approximately 10 mL of blood will be drawn from patients willing to participate. This will be done in the usual fashion, preparing the venipuncture site with the local anesthetic EMLA, then drawing blood through a small gauge (23 or 21) butterfly needle. Drawing blood from a vein may be associated with discomfort or bruising at the site of needle puncture. Rarely, fainting or infection at the site of needle puncture may occur. All blood will be drawn from a person trained in phlebotomy. There will be no way to trace the blood back to the donor.
There are no known health risks for donating saliva or tongue scrapings from individuals who will be included in the study. There is a very minimal risk of linking individuals to the study. There will be no way to trace the saliva or tongue scrapings back to the donor.
Protections Against Risk Strategies for protection against risk. To protect privacy of participants and confidentiality of research data, no personal information regarding individual participants will be linked to the in vitro studies.
Plans for medical attention. In case of injury (which is extremely unlikely) as a result of saliva donation, the individuals will be instructed to contact their physician and medical care will be offered and charged to available research coverage maintained at Wake Forest School of Medicine.
In case of injury as a result of blood drawing, the patients will be instructed to contact their physician and medical care will be offered and charged to available research coverage maintained at Wake Forest School of Medicine. Blood drawn on the Reynolda campus is not a clinical setting, but blood will be drawn by trained phlebotomists with years of experience who maintain their training.
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes will be promptly reported by the principal investigator or designated member of the research team to the IRB and sponsor or appropriate government agency if appropriate.
Incidental Findings. No incidental findings are expected to be discovered in this study as measures of bacterial nitrate reduction are not currently of clinical relevance so a strange, individual result in that measure would not be worth communicating.
Sample size assessment and statistical analysis
The investigators plan to enroll 10 participants who receive the probiotic and 10 participants who receive the placebo. The investigators hypothesize that, using a paired t-test, participants taking the probiotic will have significantly (P \< .05) lower change in plasma nitrite (post minus pre) at follow up compared to baseline while there will be no significant effect of the placebo (paired t-test).
The Investigators calculated that they would have 80% power to measure a 75% decrease in the change in nitrite at follow-up compared to baseline for the probiotic group with 10 participants per group (Continuous endpoint Two independent samples). The investigators assumed a 60% standard deviation in the change in nitrite for follow-up vs baseline based on previous data from our lab.
Conditions
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Hypertension
Cardiovascular Diseases
Diabetes
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Participants will be randomized into two groups with one group receiving the oral probiotic and the other receiving the placebo. Each group will take their intervention 2X a day for 7 days.
Primary Study Purpose
BASIC_SCIENCE
Blinding Strategy
SINGLE
Participants
Participants will not know which group they are in. The lozenges will be distributed in unmarked bottles
Study Groups
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Probiotic
Participants will take the commercially available oral probiotic (Herbiotics Oral + Ent Probiotic) twice a day for 7 days as instructed by the manufacturer. This entails one lozenge twice a day taken by mouth and slowly chewed or allowed to melt in the mouth.
Group Type
ACTIVE_COMPARATOR
Herbiotics Oral + Ent Probiotic
Intervention Type
DIETARY_SUPPLEMENT
Chewable Tablets containing Lactobacillus species.
Placebo
Participants will take the commercially available Honest Placebo Pills by Zeebo twice a day for 7 days. This entails one tablet twice a day taken by mouth and slowly chewed or allowed to melt in the mouth.
Group Type
PLACEBO_COMPARATOR
Placebo
Intervention Type
DIETARY_SUPPLEMENT
Honest Placebo Pills by Zeebo
Interventions
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Herbiotics Oral + Ent Probiotic
Chewable Tablets containing Lactobacillus species.
Intervention Type
DIETARY_SUPPLEMENT
Placebo
Honest Placebo Pills by Zeebo
Intervention Type
DIETARY_SUPPLEMENT
Eligibility Criteria
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Inclusion Criteria
* Healthy adult volunteers ages 18-70
Exclusion Criteria
* Individuals with a history of difficult blood draws. More than 2 blood draws in one week; on anti-coagulant or anti-platelet therapy (e.g. aspirin, Coumadin, etc.); known pregnancy; in police custody or a prisoner; common illness within 2 weeks of potential enrollment. The cumulative volume of blood drawn from a healthy adult over the prior eight-week period would exceed 550 ml including the current draw.
* In addition, individuals uncomfortable spitting into a tube, dry mouth (xerostomia) or dry eyes, Patients suffering from autoimmune diseases such as Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, or progressive systemic sclerosis, since individuals with these autoimmune inflammatory diseases exhibit persistent xerostomia, individuals with active caries diagnosis or history of periodontitis
* In addition, individuals uncomfortable spitting into a tube, dry mouth (xerostomia) or dry eyes, Patients suffering from autoimmune diseases such as Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, or progressive systemic sclerosis, since individuals with these autoimmune inflammatory diseases exhibit persistent xerostomia, individuals with active caries diagnosis or history of periodontitis
Minimum Eligible Age
18 Years
Maximum Eligible Age
70 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
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University of South Florida
OTHER
Sponsor Role
collaborator
Wake Forest University
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Locations
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Wake Forest University
Winston-Salem, North Carolina, United States
Site Status
RECRUITING
Countries
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United States
Central Contacts
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Facility Contacts
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References
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Leiva A, Fuenzalida B, Barros E, Sobrevia B, Salsoso R, Saez T, Villalobos R, Silva L, Chiarello I, Toledo F, Gutierrez J, Sanhueza C, Pardo F, Sobrevia L. Nitric Oxide is a Central Common Metabolite in Vascular Dysfunction Associated with Diseases of Human Pregnancy. Curr Vasc Pharmacol. 2016;14(3):237-59. doi: 10.2174/1570161114666160222115158.
Reference Type
BACKGROUND
Almeida CB, Souza LE, Leonardo FC, Costa FT, Werneck CC, Covas DT, Costa FF, Conran N. Acute hemolytic vascular inflammatory processes are prevented by nitric oxide replacement or a single dose of hydroxyurea. Blood. 2015 Aug 6;126(6):711-20. doi: 10.1182/blood-2014-12-616250. Epub 2015 May 27.
Reference Type
BACKGROUND
Maley JH, Lasker GF, Kadowitz PJ. Nitric oxide and disorders of the erythrocyte: emerging roles and therapeutic targets. Cardiovasc Hematol Disord Drug Targets. 2010 Dec 1;10(4):284-91. doi: 10.2174/187152910793743878.
Reference Type
BACKGROUND
Eisenhut M. Severe hemolysis as a potential contributing factor in the pathophysiology of cerebral malaria. Clin Infect Dis. 2015 Apr 1;60(7):1138. doi: 10.1093/cid/ciu1149. Epub 2014 Dec 19. No abstract available.
Reference Type
BACKGROUND
Donadee C, Raat NJ, Kanias T, Tejero J, Lee JS, Kelley EE, Zhao X, Liu C, Reynolds H, Azarov I, Frizzell S, Meyer EM, Donnenberg AD, Qu L, Triulzi D, Kim-Shapiro DB, Gladwin MT. Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesion. Circulation. 2011 Jul 26;124(4):465-76. doi: 10.1161/CIRCULATIONAHA.110.008698. Epub 2011 Jul 11.
Reference Type
BACKGROUND
Gladwin MT, Kim-Shapiro DB. Storage lesion in banked blood due to hemolysis-dependent disruption of nitric oxide homeostasis. Curr Opin Hematol. 2009 Nov;16(6):515-23. doi: 10.1097/MOH.0b013e32833157f4.
Reference Type
BACKGROUND
Hirai DM, Musch TI, Poole DC. Exercise training in chronic heart failure: improving skeletal muscle O2 transport and utilization. Am J Physiol Heart Circ Physiol. 2015 Nov;309(9):H1419-39. doi: 10.1152/ajpheart.00469.2015. Epub 2015 Aug 28.
Reference Type
BACKGROUND
Voetsch B, Jin RC, Loscalzo J. Nitric oxide insufficiency and atherothrombosis. Histochem Cell Biol. 2004 Oct;122(4):353-67. doi: 10.1007/s00418-004-0675-z. Epub 2004 Aug 26.
Reference Type
BACKGROUND
Bertoluci MC, Ce GV, da Silva AM, Wainstein MV, Boff W, Punales M. Endothelial dysfunction as a predictor of cardiovascular disease in type 1 diabetes. World J Diabetes. 2015 Jun 10;6(5):679-92. doi: 10.4239/wjd.v6.i5.679.
Reference Type
BACKGROUND
Kapil V, Haydar SM, Pearl V, Lundberg JO, Weitzberg E, Ahluwalia A. Physiological role for nitrate-reducing oral bacteria in blood pressure control. Free Radic Biol Med. 2013 Feb;55:93-100. doi: 10.1016/j.freeradbiomed.2012.11.013. Epub 2012 Nov 23.
Reference Type
BACKGROUND
Govoni M, Jansson EA, Weitzberg E, Lundberg JO. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide. 2008 Dec;19(4):333-7. doi: 10.1016/j.niox.2008.08.003. Epub 2008 Aug 30.
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Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
IRB00025485
Identifier Type: -
Identifier Source: org_study_id
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