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Completed

NCT Number: NCT01681836

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.

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Key information

Conditions

Focus of Study of Healthy Adults

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Montefiore Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

15Nitrogen(15N)-labeled sodium nitrite

Drug

15Nitrogen(15N)-labeled sodium nitrite 20 mg once

15Nitrogen(15N)-labeled sodium nitrate

Drug

15Nitrogen(15N)-labeled sodium nitrate 1,000 mg once

Primary outcomes

  1. Peak Plasma Nitrate Concentration Over 24 Hour Study Period

    Time frame: 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

  2. Peak Plasma Nitrite Concentration Over 24 Hour Study Period

    Time frame: 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

  3. Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period

    Time frame: 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

Secondary outcomes

  1. Peak Percentage Level of Methemoglobin Over 24 Hour Study Period

    Time frame: 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

  2. Peak Change in Mean Arterial Pressure Over 24 Hour Study Period

    Time frame: 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

  3. Peak Change in Systolic Blood Pressure Over 24 Hour Study Period

    Time frame: 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

  4. Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period

    Time frame: 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

  5. Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period

    Time frame: 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

  6. Percent Platelet Activation at 6 Hours

    Time frame: 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

  7. Peak Change in Heart Rate Over 24 Hour Study Period

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Gladwin, Mark, MD

Indiv

Registry information

Official study title

An Open-Label Study of Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
Sep 10, 2012
Registry last updated
Sep 4, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.