Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
31 de agosto de 2018 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
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 de estudio
Intervencionista
Inscripción (Actual)
11
Fase
- Fase 1
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15213
- Montefiore Hospital of UPMC
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 60 años (Adulto)
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Todos
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Otro
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: 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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Experimental: 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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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Peak Plasma Nitrate Concentration Over 24 Hour Study Period
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Peak Percentage Level of Methemoglobin Over 24 Hour Study Period
Periodo de tiempo: 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
Periodo de tiempo: 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 Change in Systolic Blood Pressure Over 24 Hour Study Period
Periodo de tiempo: 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
Periodo de tiempo: 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
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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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
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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), 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
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Kara S Hughan, MD, University of Pittsburgh
- Director de estudio: Mark T Gladwin, MD, University of Pittsburgh
- Director de estudio: Bret Goodpaster, PhD, University of Pittsburgh
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de octubre de 2012
Finalización primaria (Actual)
1 de octubre de 2013
Finalización del estudio (Actual)
1 de octubre de 2013
Fechas de registro del estudio
Enviado por primera vez
3 de julio de 2012
Primero enviado que cumplió con los criterios de control de calidad
5 de septiembre de 2012
Publicado por primera vez (Estimar)
10 de septiembre de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
4 de septiembre de 2018
Última actualización enviada que cumplió con los criterios de control de calidad
31 de agosto de 2018
Última verificación
1 de agosto de 2018
Más información
Términos relacionados con este estudio
Otros números de identificación del estudio
- PRO11120134
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .