Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
31. August 2018 aktualisiert von: Kara Hughan, Gladwin, Mark, MD
An Open-Label Study of Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
This proposal hypothesizes that oral supplementation with sodium nitrite or nitrate will result in in vivo conversion of nitrate to nitrite and nitrite to nitric oxide with limited toxicity in the doses proposed in healthy adult normal volunteers.
We utilize a powerful in vivo technique (pharmacokinetic testing) and are the first to design inorganic nitrate and nitrite capsules for cardiovascular disease.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
Preclinical and clinical research over the last decade has revealed the important vasoprotective effects of nitrates and nitrites with regards to reduction in blood pressure, vascular inflammation and endothelial dysfunction. New findings suggest an effect of nitrate and nitrite therapy in the regulation of glucose-insulin homeostasis. Development of an oral formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the nitrate would continuously provide a slow formation of nitrite over a prolonged period of time via the enterosalivary circulation pathway.
For this reason, development of an oral formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the nitrate would continuously provide a slow formation of nitrite over a prolonged period of time via the enterosalivary circulation pathway. This study aims to establish the pharmacokinetics, metabolism and interconversion of nitrate to nitrite and nitrite to nitric oxide in vivo in healthy adult normal volunteers.
Studientyp
Interventionell
Einschreibung (Tatsächlich)
11
Phase
- Phase 1
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
-
Pennsylvania
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Pittsburgh, Pennsylvania, Vereinigte Staaten, 15213
- Montefiore Hospital of UPMC
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 60 Jahre (Erwachsene)
Akzeptiert gesunde Freiwillige
Ja
Studienberechtigte Geschlechter
Alle
Beschreibung
Inclusion Criteria:
- Age 18-60 years
- Systolic blood pressure ≤130 and diastolic blood pressure ≤85 mm Hg
Exclusion Criteria:
- Positive urine pregnancy test or breastfeeding
- Concurrent use of medications affecting glucose or lipid metabolism
- Recent addition or change in dosing of hormonal contraceptive medications (oral contraceptive pill, intrauterine device, DepoProvera)
- Current use of ≥2 anti-hypertensive agents regardless of blood pressure control or normotensive on a single agent
- Current use of phosphodiesterase 5 inhibitors or organic nitrates
- Not stable on treatments for the prior three months or not planning to remain on current dose of medications for blood pressure, contraception, etc
- Known chronic psychiatric or medical conditions including diabetes, liver or kidney disease or obesity syndromes
- Smoker
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Sonstiges
- Zuteilung: Zufällig
- Interventionsmodell: Crossover-Aufgabe
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: Oral 15N-labeled sodium nitrate
Oral sodium nitrate 1,000 mg once first, then washout followed by oral sodium nitrite 20 mg once
|
15Nitrogen(15N)-labeled sodium nitrite 20 mg once
15Nitrogen(15N)-labeled sodium nitrate 1,000 mg once
|
|
Experimental: Oral 15N-labeled sodium nitrite
Oral sodium nitrite 20 mg once first, then washout followed by oral sodium nitrate 1,000 mg once
|
15Nitrogen(15N)-labeled sodium nitrite 20 mg once
15Nitrogen(15N)-labeled sodium nitrate 1,000 mg once
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Peak Plasma Nitrate Concentration Over 24 Hour Study Period
Zeitfenster: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
|
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
|
measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
|
|
Peak Plasma Nitrite Concentration Over 24 Hour Study Period
Zeitfenster: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
|
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
|
measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
|
|
Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period
Zeitfenster: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
|
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
|
measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Peak Percentage Level of Methemoglobin Over 24 Hour Study Period
Zeitfenster: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
|
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
|
measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
|
|
Peak Change in Mean Arterial Pressure Over 24 Hour Study Period
Zeitfenster: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported
|
"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
|
measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported
|
|
Peak Change in Systolic Blood Pressure Over 24 Hour Study Period
Zeitfenster: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours reported
|
"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
|
measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours reported
|
|
Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period
Zeitfenster: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported
|
"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
|
measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported
|
|
Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period
Zeitfenster: measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose
|
"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
|
measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose
|
|
Percent Platelet Activation at 6 Hours
Zeitfenster: measured at 0 (baseline), 6 and 24 hours post-dose
|
at timepoint with greatest change from 0 (trough); "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period; percentage of platelets that express 2 specific markers identifying activated platelets (CD41 and CD62-P) were quantified using flow cytometry
|
measured at 0 (baseline), 6 and 24 hours post-dose
|
|
Peak Change in Heart Rate Over 24 Hour Study Period
Zeitfenster: measured at 0 (baseline), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours for nitrate and 24 hours for nitrite
|
"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
|
measured at 0 (baseline), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours for nitrate and 24 hours for nitrite
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Ermittler
- Hauptermittler: Kara S Hughan, MD, University of Pittsburgh
- Studienleiter: Mark T Gladwin, MD, University of Pittsburgh
- Studienleiter: Bret Goodpaster, PhD, University of Pittsburgh
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn
1. Oktober 2012
Primärer Abschluss (Tatsächlich)
1. Oktober 2013
Studienabschluss (Tatsächlich)
1. Oktober 2013
Studienanmeldedaten
Zuerst eingereicht
3. Juli 2012
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
5. September 2012
Zuerst gepostet (Schätzen)
10. September 2012
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
4. September 2018
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
31. August 2018
Zuletzt verifiziert
1. August 2018
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Andere Studien-ID-Nummern
- PRO11120134
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