Oral Nitrite in Adults With Metabolic Syndrome and Hypertension
Condition: Metabolic Syndrome; Hypertension
MeSH terms: Hypertension; Metabolic Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      This research study is being conducted to examine the effects of daily inorganic nitrite
      treatment on the cardiometabolic and hormonal disturbances observed in overweight/obese
      adults with the metabolic syndrome and high blood pressure. Ultimately, oral nitrite therapy
      may have a major impact on the prevention and treatment of both diabetes and cardiovascular
      disease.
    

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 which can be further 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 is the first human study to investigate the inorganic nitrite
      effects (in any form) on insulin sensitivity in a patient population. This is the second
      human trial using orally delivered nitrite (previously as aqueous solution).

      In the initial phase of the study, step up dosing and frequency of oral sodium nitrite to 40
      mg three times daily occurred with no serious adverse events. After three subjects completed
      the study intervention on sodium nitrite 20 mg three times daily for 2 weeks followed by 40
      mg three times daily for the remaining 10 weeks with no serious adverse events, all subjects
      in this current phase of the trial (n=20) began the 12-week study intervention with 40 mg
      three times daily. At the same time, in person monitoring visits (which included brief
      physical exams, directly observed nitrite dosing, secondary outcome measure assessment of
      methemoglobin level and blood pressure, interval histories, medication compliance review,
      symptom review and dispensing of study drug) were spaced from weekly intervals to subjects
      alternating weekly in person visits with phone visits.
    

Intervention name(s): 14Nitrogen Sodium Nitrite
Intervention type(s): Drug
Intervention description(s): oral formulation of sodium nitrite 40 mg three times a day for 12 weeks
Other intervention name(s): sodium nitrite
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment