Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
Kara Hughan, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01681836
First received: July 3, 2012
Last updated: January 30, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Healthy Adult Normal Volunteers
Drug: Non-radioactive "heavy" 15N-labeled sodium nitrite
Drug: 15N-labeled sodium nitrate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: An Open-Label Study of Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Change from baseline in nitrate, nitrite, nitric oxide concentrations over 24 hours [ Time Frame: 0 (trough), then 0.5, 1, 2, 3, 6 and 24 hours post-doses ] [ Designated as safety issue: No ]
    "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


Secondary Outcome Measures:
  • Change from baseline in methemoglobin % over 24 hours [ Time Frame: 0 (trough), then 0.5, 1, 2, 3, 6 and 24 hours post-doses ] [ Designated as safety issue: Yes ]
    "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

  • Change from baseline in heart rate over 24 hours [ Time Frame: time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose ] [ Designated as safety issue: No ]
    "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

  • Change from baseline in mean arterial pressure over 24 hours [ Time Frame: time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose ] [ Designated as safety issue: Yes ]
    "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

  • Change from baseline in blood pressure over 24 hours [ Time Frame: time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose ] [ Designated as safety issue: No ]
    "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

  • Change from baseline in nitro-fatty acids concentration over 24 hours [ Time Frame: time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose ] [ Designated as safety issue: No ]
    "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

  • Change from baseline in platelet mitochondrial function over 24 hours [ Time Frame: 0 (trough) and 6 hours post-dose ] [ Designated as safety issue: No ]
    "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


Estimated Enrollment: 10
Study Start Date: October 2012
Intervention Details:
    Drug: Non-radioactive "heavy" 15N-labeled sodium nitrite
    15N-labeled sodium nitrite 20 mg once
    Drug: 15N-labeled sodium nitrate
    15N-labeled sodium nitrate 1,000 mg once
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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
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 (OCP, IUD, DepoProvera)
  • Current use of ≥2 anti-hypertensive agents regardless of blood pressure control or normotensive on a single agent
  • Current use of PD5 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01681836

Contacts
Contact: Kara S Hughan, MD 412-692-5173 kara.hughan@chp.edu

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

No publications provided

Responsible Party: Kara Hughan, Instructor of Pediatrics, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01681836     History of Changes
Other Study ID Numbers: PRO11120134
Study First Received: July 3, 2012
Last Updated: January 30, 2013
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on October 23, 2014