NCT02517697

Oral Nitrite Trial for Hypertension and Metabolic Syndrome

Nitrite Modulation of Hypertension, Platelet Activation, and Endothelial and Mitochondrial Function

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Gladwin, Mark, MD · Individual
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

The objective of the study is to investigate effects of inorganic sodium nitrite on the cardiometabolic and hormonal disturbances observed in a targeted population of overweight/obese adults with metabolic syndrome and hypertension, at risk for insulin resistance and endothelial dysfunction.

Detailed description

Cardiovascular disease remains the leading cause of death in the United States and worldwide. Several studies have demonstrated that fruit and vegetable rich diets significantly reduced blood pressure and reduced the risk of ischemic stroke and cardiovascular disease in general, the exact mechanisms remain poorly understood. 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. More recent findings suggest that inorganic nitrate and nitrite therapy may be involved in the regulation of glucose-insulin homeostasis. For this reason, development of an oral formulation of nitrite salt represents a rational avenue of exploration for the treatment of cardiovascular diseases, whereby nitrite would ensure rapid acting effects upon absorption. Nitrite could then be oxidized to nitrate via the enterosalivary circulation pathway. In this pathway, about 25% of circulating nitrate is concentrated in the saliva and reduced to nitrite by commensal mouth bacteria with nitrate reductase enzymes. The proposal will investigate the inorganic nitrite effects (in any form) on insulin sensitivity in a targeted population of overweight/obese adults with metabolic syndrome and hypertension, at risk for insulin resistance and endothelial dysfunction. This will be the third human trial using orally delivered nitrite (previously as aqueous solution).

Conditions

• Metabolic Syndrome
• Hypertension

Interventions

Type	Name	Description
DRUG	14 Nitrogen (N) Sodium Nitrite	oral formulation of sodium nitrite 40 mg three times daily for 12 weeks
DRUG	Placebo	oral formulation of matching placebo three times daily for 12 weeks

Timeline

• Start date: 2020-10-01
• Primary completion: 2021-04-13
• Completion: 2021-04-13
• First posted: 2015-08-07
• Last updated: 2021-04-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study