Oral Nitrite in Adults With Metabolic Syndrome and Hypertension
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Endocrine |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 4/17/2018 |
| Start Date: | October 2012 |
An Open-Label Study of Oral Nitrite in Adults With Metabolic Syndrome and Hypertension
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.
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.
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 will be the second
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 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 will be the second
human trial using orally delivered nitrite (previously as aqueous solution).
Inclusion Criteria:
- Age 18-60 years
- 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 (OCP), intrauterine device (IUD), DepoProvera]
- 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 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
- Thyroid-stimulating hormone (TSH) >8 milli-International unit/mL
- Smoker
We found this trial at
1
site
Pittsburgh, Pennsylvania 15213
Principal Investigator: Kara S Hughan, MD
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