Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
31. august 2018 opdateret af: 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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret 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.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
11
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
Pennsylvania
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Pittsburgh, Pennsylvania, Forenede Stater, 15213
- Montefiore Hospital of UPMC
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 60 år (Voksen)
Tager imod sunde frivillige
Ja
Køn, der er berettiget til at studere
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
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Andet
- Tildeling: Randomiseret
- Interventionel model: Crossover opgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: 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
|
|
Eksperimentel: 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
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
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 |
Foranstaltningsbeskrivelse |
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
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Kara S Hughan, MD, University of Pittsburgh
- Studieleder: Mark T Gladwin, MD, University of Pittsburgh
- Studieleder: Bret Goodpaster, PhD, University of Pittsburgh
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. oktober 2012
Primær færdiggørelse (Faktiske)
1. oktober 2013
Studieafslutning (Faktiske)
1. oktober 2013
Datoer for studieregistrering
Først indsendt
3. juli 2012
Først indsendt, der opfyldte QC-kriterier
5. september 2012
Først opslået (Skøn)
10. september 2012
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
4. september 2018
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
31. august 2018
Sidst verificeret
1. august 2018
Mere information
Begreber relateret til denne undersøgelse
Andre undersøgelses-id-numre
- PRO11120134
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .