Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
31. august 2018 oppdatert av: 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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Intervensjonell
Registrering (Faktiske)
11
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
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Pennsylvania
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Pittsburgh, Pennsylvania, Forente stater, 15213
- Montefiore Hospital of UPMC
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 60 år (Voksen)
Tar imot friske frivillige
Ja
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Annen
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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
|
|
Eksperimentell: 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
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Peak Plasma Nitrate Concentration Over 24 Hour Study Period
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Peak Percentage Level of Methemoglobin Over 24 Hour Study Period
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Hovedetterforsker: Kara S Hughan, MD, University of Pittsburgh
- Studieleder: Mark T Gladwin, MD, University of Pittsburgh
- Studieleder: Bret Goodpaster, PhD, University of Pittsburgh
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. oktober 2012
Primær fullføring (Faktiske)
1. oktober 2013
Studiet fullført (Faktiske)
1. oktober 2013
Datoer for studieregistrering
Først innsendt
3. juli 2012
Først innsendt som oppfylte QC-kriteriene
5. september 2012
Først lagt ut (Anslag)
10. september 2012
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
4. september 2018
Siste oppdatering sendt inn som oppfylte QC-kriteriene
31. august 2018
Sist bekreftet
1. august 2018
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- PRO11120134
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