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Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults

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ClinicalTrials.gov Identifier: NCT01681836
Recruitment Status : Completed
First Posted : September 10, 2012
Results First Posted : September 3, 2018
Last Update Posted : September 3, 2018
Sponsor:
Information provided by (Responsible Party):
Kara Hughan, University of Pittsburgh

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Focus of Study of Healthy Adults Drug: 15Nitrogen(15N)-labeled sodium nitrite Drug: 15Nitrogen(15N)-labeled sodium nitrate Phase 1

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open-Label Study of Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
Study Start Date : October 2012
Actual Primary Completion Date : October 2013
Actual Study Completion Date : October 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Oral 15N-labeled sodium nitrate
Oral sodium nitrate 1,000 mg once first, then washout followed by oral sodium nitrite 20 mg once
Drug: 15Nitrogen(15N)-labeled sodium nitrite
15Nitrogen(15N)-labeled sodium nitrite 20 mg once

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

Experimental: Oral 15N-labeled sodium nitrite
Oral sodium nitrite 20 mg once first, then washout followed by oral sodium nitrate 1,000 mg once
Drug: 15Nitrogen(15N)-labeled sodium nitrite
15Nitrogen(15N)-labeled sodium nitrite 20 mg once

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




Primary Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01681836


Locations
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United States, Pennsylvania
Montefiore Hospital of UPMC
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Gladwin, Mark, MD
Investigators
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Principal Investigator: Kara S Hughan, MD University of Pittsburgh
Study Director: Mark T Gladwin, MD University of Pittsburgh
Study Director: Bret Goodpaster, PhD University of Pittsburgh

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kara Hughan, Instructor of Pediatrics, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01681836     History of Changes
Other Study ID Numbers: PRO11120134
First Posted: September 10, 2012    Key Record Dates
Results First Posted: September 3, 2018
Last Update Posted: September 3, 2018
Last Verified: August 2018