Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults

Gladwin, Mark, MD

Status and phase: Completed; Phase 1

Conditions: Focus of Study of Healthy Adults

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

Study type: Interventional

Identifiers

NCT01681836

PRO11120134

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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11 participants in 2 patient groups

Oral 15N-labeled sodium nitrate

Experimental group

Description:

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

Treatment:

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

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

Oral 15N-labeled sodium nitrite

Experimental group

Description:

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

Treatment:

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

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