Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Oral Nitrite and Nitrate in Adults With Metabolic Syndrome and Hypertension

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
Kara Hughan, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01681810
First received: July 3, 2012
Last updated: January 30, 2013
Last verified: January 2013

July 3, 2012
January 30, 2013
October 2012
Not Provided
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
Same as current
Complete list of historical versions of study NCT01681810 on ClinicalTrials.gov Archive Site
  • 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 weekly 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 weekly throughout the 12 week treatment ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Oral Nitrite and Nitrate in Adults With Metabolic Syndrome and Hypertension
An Open-Label Study of Oral Combination of Nitrite and Nitrate in Adults With Metabolic Syndrome and Hypertension

This research study is being conducted to examine the effects of daily inorganic nitrate and nitrite treatment on the cardiometabolic and hormonal disturbances observed in overweight/obese adults with the metabolic syndrome and high blood pressure. Ultimately, oral nitrate and 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 nitrate and nitrite salts represents a rational avenue of exploration for the treatment of cardiovascular diseases, whereby nitrite would ensure rapid acting effects upon absorption, while the nitrate would continuously provide a slow formation of nitrite over a prolonged period of time 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 nitrate or nitrite effects (in any form) on insulin sensitivity in a patient population. This will be the third human trial using orally delivered inorganic nitrate capsules in normal volunteers or subjects with hypertension and the second human trial using orally delivered nitrite (previously as aqueous solution).

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Metabolic Syndrome
  • Hypertension
  • Drug: 14 N Sodium Nitrite
    oral formulation of sodium nitrite 20 mg daily for 12 weeks
    Other Name: sodium nitrite
  • Drug: 14 N Sodium Nitrate
    oral formulation of sodium nitrate 1,000 mg daily for 12 weeks
    Other Name: sodium nitrate
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
Not Provided
Not Provided

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 or lipid metabolism (oral hypoglycemics, insulin, statins, atypical antipsychotics)
  • Recent addition or change in dosing of hormonal contraceptive medications (OCP, IUD, DepoProvera)
  • Current use of ≥2 anti-hypertensive agents regardless of blood pressure control or normotensive on a single 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
Both
18 Years to 60 Years
No
Contact: Kara S Hughan, MD 412-692-5173
United States
 
NCT01681810
PRO11030131
No
Kara Hughan, University of Pittsburgh
University of Pittsburgh
Not Provided
Principal Investigator: Kara S Hughan, MD University of Pittsburgh
Study Director: Mark Gladwin, MD University of Pittsburgh
Study Director: Bret Goodpaster, PhD University of Pittsburgh
University of Pittsburgh
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP