Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults

NCT ID: NCT01681836

Last Updated: 2018-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2013-10-31

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.

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.

Conditions

Focus of Study of Healthy Adults

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Oral 15N-labeled sodium nitrate

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

Group Type: EXPERIMENTAL

15Nitrogen(15N)-labeled sodium nitrite

Intervention Type: DRUG

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

15Nitrogen(15N)-labeled sodium nitrate

Intervention Type: DRUG

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

Oral 15N-labeled sodium nitrite

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

Group Type: EXPERIMENTAL

15Nitrogen(15N)-labeled sodium nitrite

Intervention Type: DRUG

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

15Nitrogen(15N)-labeled sodium nitrate

Intervention Type: DRUG

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

Interventions

15Nitrogen(15N)-labeled sodium nitrite

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

Intervention Type: DRUG

15Nitrogen(15N)-labeled sodium nitrate

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

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gladwin, Mark, MD

INDIV

Sponsor Role: lead

Responsible Party

Kara Hughan

Instructor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kara S Hughan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Mark T Gladwin, MD

Role: STUDY_DIRECTOR

University of Pittsburgh

Bret Goodpaster, PhD

Role: STUDY_DIRECTOR

University of Pittsburgh

Locations

Montefiore Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28739973 (View on PubMed)

Other Identifiers

PRO11120134

Identifier Type: -

Identifier Source: org_study_id