Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
31 agosto 2018 aggiornato da: 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.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
11
Fase
- Fase 1
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Pennsylvania
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Pittsburgh, Pennsylvania, Stati Uniti, 15213
- Montefiore Hospital of UPMC
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 18 anni a 60 anni (Adulto)
Accetta volontari sani
Sì
Sessi ammissibili allo studio
Tutto
Descrizione
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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Altro
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione incrociata
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: Oral 15N-labeled sodium nitrate
Oral sodium nitrate 1,000 mg once first, then washout followed by oral sodium nitrite 20 mg once
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15Nitrogen(15N)-labeled sodium nitrite 20 mg once
15Nitrogen(15N)-labeled sodium nitrate 1,000 mg once
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Sperimentale: Oral 15N-labeled sodium nitrite
Oral sodium nitrite 20 mg once first, then washout followed by oral sodium nitrate 1,000 mg once
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15Nitrogen(15N)-labeled sodium nitrite 20 mg once
15Nitrogen(15N)-labeled sodium nitrate 1,000 mg once
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Peak Plasma Nitrate Concentration Over 24 Hour Study Period
Lasso di tempo: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
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"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
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measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
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Peak Plasma Nitrite Concentration Over 24 Hour Study Period
Lasso di tempo: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
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"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
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measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
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Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period
Lasso di tempo: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
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"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
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Peak Percentage Level of Methemoglobin Over 24 Hour Study Period
Lasso di tempo: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
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"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
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Peak Change in Mean Arterial Pressure Over 24 Hour Study Period
Lasso di tempo: 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
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"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
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Peak Change in Systolic Blood Pressure Over 24 Hour Study Period
Lasso di tempo: 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
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"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
|
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Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period
Lasso di tempo: 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
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"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
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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
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Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period
Lasso di tempo: measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose
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"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
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measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose
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Percent Platelet Activation at 6 Hours
Lasso di tempo: measured at 0 (baseline), 6 and 24 hours post-dose
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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
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measured at 0 (baseline), 6 and 24 hours post-dose
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Peak Change in Heart Rate Over 24 Hour Study Period
Lasso di tempo: 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
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Investigatori
- Investigatore principale: Kara S Hughan, MD, University of Pittsburgh
- Direttore dello studio: Mark T Gladwin, MD, University of Pittsburgh
- Direttore dello studio: Bret Goodpaster, PhD, University of Pittsburgh
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 ottobre 2012
Completamento primario (Effettivo)
1 ottobre 2013
Completamento dello studio (Effettivo)
1 ottobre 2013
Date di iscrizione allo studio
Primo inviato
3 luglio 2012
Primo inviato che soddisfa i criteri di controllo qualità
5 settembre 2012
Primo Inserito (Stima)
10 settembre 2012
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
4 settembre 2018
Ultimo aggiornamento inviato che soddisfa i criteri QC
31 agosto 2018
Ultimo verificato
1 agosto 2018
Maggiori informazioni
Termini relativi a questo studio
Altri numeri di identificazione dello studio
- PRO11120134
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Focus of Study of Healthy Adults
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InQpharm GroupCompletatoPerdita di peso | Modulazione dell'appetito (Focus of Study)Germania