Oral Nitrite Trial for Hypertension and Metabolic Syndrome (ONPC)

Gladwin, Mark, MD

Status and phase

Withdrawn

Phase 2

Conditions

Hypertension

Metabolic Syndrome

Treatments

Drug: 14 Nitrogen (N) Sodium Nitrite

Drug: Placebo

Study type

Interventional

Identifiers

NCT02517697

PRO15050540

Details and patient eligibility

About

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.

Full 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).

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 18-60 years
Body mass index (BMI) ≥ 30 kg/m2
Hypertension: defined as systolic blood pressure ≥130 and/or diastolic blood pressure ≥85 mm Hg
Waist circumference: >102 cm in men, >88 cm in women

Exclusion criteria

Positive urine pregnancy test or breastfeeding
Concurrent use of medications affecting glucose metabolism (oral hypoglycemics, insulin, atypical antipsychotics)
Recent addition or change in dosing of hormonal contraceptive medications (Oral Contraceptive Pill (OCP), Intra Uterine Device (IUD), DepoProvera shot)
Current use of ≥3 anti-hypertensive agents regardless of blood pressure control or normotensive on a single or double agent
Current use of phosphodiesterase-5 (PD) inhibitors or organic nitrates. We will not exclude for dietary sources of nitrate/nitrite.
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
Thyroid Stimulating Hormone (TSH) >8 milli-International unit/mL
Smoker
Anemia (central lab hemoglobin < 11g/dL)
Active periodontal disease