Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults

NCT01681836 | Completed Phase 1 Results

• 1 other identifier: PRO11120134
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Focus of Study of Healthy Adults

Outcome Measures

Primary Outcomes (3)

• Peak Plasma Nitrate Concentration Over 24 Hour Study Period

  "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

  "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

  "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

Secondary Outcomes (7)

• Peak Percentage Level of Methemoglobin Over 24 Hour Study 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

  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

  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

  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

  measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose

Study Arms (2)

Oral 15N-labeled sodium nitrate

EXPERIMENTAL

Oral sodium nitrate 1,000 mg once first, then washout followed by oral sodium nitrite 20 mg once

Drug: 15Nitrogen(15N)-labeled sodium nitrite; Drug: 15Nitrogen(15N)-labeled sodium nitrate

Oral 15N-labeled sodium nitrite

EXPERIMENTAL

Oral sodium nitrite 20 mg once first, then washout followed by oral sodium nitrate 1,000 mg once

Drug: 15Nitrogen(15N)-labeled sodium nitrite; Drug: 15Nitrogen(15N)-labeled sodium nitrate

Interventions

15Nitrogen(15N)-labeled sodium nitrite DRUG

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

Oral 15N-labeled sodium nitrate; Oral 15N-labeled sodium nitrite

15Nitrogen(15N)-labeled sodium nitrate DRUG

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

Oral 15N-labeled sodium nitrate; Oral 15N-labeled sodium nitrite

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60 years
• Systolic blood pressure ≤130 and diastolic blood pressure ≤85 mm Hg

You may not qualify if:

• 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

Sponsors & Collaborators

• Gladwin, Mark, MD: lead

Study Sites (1)

Montefiore Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Hughan KS, Wendell SG, Delmastro-Greenwood M, Helbling N, Corey C, Bellavia L, Potti G, Grimes G, Goodpaster B, Kim-Shapiro DB, Shiva S, Freeman BA, Gladwin MT. Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate. Hypertension. 2017 Sep;70(3):634-644. doi: 10.1161/HYPERTENSIONAHA.117.09016.

  PMID: 28739973 DERIVED

Results Point of Contact

• Title: Dr. Kara Hughan
• Organization: University of Pittsburgh

kara.hughan@chp.edu

412-692-5170

Study Officials

• Kara S Hughan, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Mark T Gladwin, MD

  University of Pittsburgh

  STUDY DIRECTOR

• Bret Goodpaster, PhD

  University of Pittsburgh

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor of Pediatrics

Study Record Dates

• First Submitted: July 3, 2012
• First Posted: September 10, 2012
• Study Start: October 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: September 4, 2018
• Results First Posted: September 4, 2018

Record last verified: 2018-08

Locations

US (1)