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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01681810
Recruitment Status : Completed
First Posted : September 10, 2012
Last Update Posted : March 7, 2018
Information provided by (Responsible Party):
Kara Hughan, University of Pittsburgh

Brief Summary:
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 or disease Intervention/treatment Phase
Metabolic Syndrome Hypertension Drug: 14Nitrogen Sodium Nitrite Phase 2

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).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study of Oral Nitrite in Adults With Metabolic Syndrome and Hypertension
Study Start Date : October 2012
Actual Primary Completion Date : February 8, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 14Nitrogen sodium nitrite
sodium nitrite 40 mg three times a day for 12 weeks
Drug: 14Nitrogen Sodium Nitrite
oral formulation of sodium nitrite 40 mg three times a day for 12 weeks
Other Name: sodium nitrite

Primary Outcome Measures :
  1. Change in insulin sensitivity (i.e. insulin stimulated glucose disposal) [ Time Frame: baseline and 12 weeks ]
    obtained by hyperinsulinemic euglycemic clamp

Secondary Outcome Measures :
  1. Change in systolic blood pressure [ Time Frame: baseline and 12 weeks ]
  2. Change in mean arterial pressure [ Time Frame: baseline and then biweekly throughout the 12 week treatment ]
  3. Change in diastolic blood pressure [ Time Frame: baseline and 12 weeks ]
  4. Change in methemoglobin level [ Time Frame: baseline and then biweekly throughout the 12 week treatment ]
    obtained by co-oximetry

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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 [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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01681810

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

Responsible Party: Kara Hughan, Assistant Professor of Pediatrics, University of Pittsburgh Identifier: NCT01681810     History of Changes
Other Study ID Numbers: PRO11030131
First Posted: September 10, 2012    Key Record Dates
Last Update Posted: March 7, 2018
Last Verified: March 2018

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