Oral Nitrite Trial for Hypertension and Metabolic Syndrome

Hypertension Clinical Trial

— ONPC  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02517697
• Other study ID #: PRO15050540
• Status: Withdrawn
• Phase: Phase 2
• Start date: October 2020
• Est. completion date: April 13, 2021

Study information

• Verified date: April 2021
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 13, 2021
• Est. primary completion date: April 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Metabolic Syndrome
• Syndrome

Intervention

Drug:
• 14 Nitrogen (N) Sodium Nitrite
oral formulation of sodium nitrite 40 mg three times daily for 12 weeks
• Placebo
oral formulation of matching placebo three times daily for 12 weeks

Locations

Country	Name	City	State
United States	Montefiore Hospital of UPMC	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Gladwin, Mark, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in insulin sensitivity (i.e. insulin stimulated glucose disposal)	obtained by hyperinsulinemic euglycemic clamp	baseline and 12 weeks
Secondary	Change in systolic blood pressure	ambulatory blood pressure	baseline and 12 weeks
Secondary	Change in mean arterial pressure	ambulatory blood pressure	baseline and then biweekly throughout the 12 week treatment
Secondary	Change in diastolic blood pressure	ambulatory blood pressure	baseline and 12 weeks
Secondary	Change in methemoglobin level	by co-oximetry	baseline and then biweekly throughout the 12 week treatment