Oral Nitrite in Adults With Metabolic Syndrome and Hypertension (ONTX)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by University of Pittsburgh
Information provided by (Responsible Party):
Kara Hughan, University of Pittsburgh
ClinicalTrials.gov Identifier:
First received: July 3, 2012
Last updated: February 18, 2016
Last verified: February 2016
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.

Condition Intervention Phase
Metabolic Syndrome
Drug: 14 N Sodium Nitrite
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Study of Oral Nitrite in Adults With Metabolic Syndrome and Hypertension

Resource links provided by NLM:

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Change in insulin sensitivity (i.e. insulin stimulated glucose disposal) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    obtained by hyperinsulinemic euglycemic clamp

Secondary Outcome Measures:
  • Change in systolic blood pressure [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in mean arterial pressure [ Time Frame: baseline and then biweekly throughout the 12 week treatment ] [ Designated as safety issue: Yes ]
  • Change in diastolic blood pressure [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in methemoglobin level [ Time Frame: baseline and then biweekly throughout the 12 week treatment ] [ Designated as safety issue: Yes ]
    obtained by co-oximetry

Estimated Enrollment: 20
Study Start Date: October 2012
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 14N sodium nitrite
sodium nitrite 40 mg TID for 12 weeks
Drug: 14 N Sodium Nitrite
oral formulation of sodium nitrite 40 mg TID for 12 weeks
Other Name: sodium nitrite

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 will be the second human trial using orally delivered nitrite (previously as aqueous solution).


Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 (OCP, 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 PD5 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
  • TSH >8 mIU/mL
  • Smoker
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01681810

Contact: Kara S Hughan, MD 412-692-5173

United States, Pennsylvania
Montefiore Hospital of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Principal Investigator: Kara S Hughan, MD         
Sub-Investigator: Mark T Gladwin, MD         
Sponsors and Collaborators
University of Pittsburgh
Principal Investigator: Kara S Hughan, MD University of Pittsburgh
Study Director: Mark Gladwin, MD University of Pittsburgh
  More Information

Responsible Party: Kara Hughan, Assistant Professor of Pediatrics, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01681810     History of Changes
Other Study ID Numbers: PRO11030131 
Study First Received: July 3, 2012
Last Updated: February 18, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Metabolic Syndrome X
Cardiovascular Diseases
Glucose Metabolism Disorders
Insulin Resistance
Metabolic Diseases
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on May 30, 2016