Oral Nitrite Trial for Hypertension and Metabolic Syndrome
| Status: | Not yet recruiting |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Endocrine |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 3/30/2019 |
| Start Date: | April 2019 |
| End Date: | June 2020 |
| Contact: | Kara S Hughan, MD |
| Email: | Kara.Hughan@chp.edu |
| Phone: | 412-692-5173 |
Nitrite Modulation of Hypertension, Platelet Activation, and Endothelial and Mitochondrial Function
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.
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.
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).
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).
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
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