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
  Purpose

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.


Condition Intervention Phase
Metabolic Syndrome
Hypertension
Drug: 14 N Sodium Nitrite
Drug: 14 N Sodium Nitrate
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 Combination of Nitrite and Nitrate 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 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 ]

Estimated Enrollment: 20
Study Start Date: October 2012
Intervention Details:
    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
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 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).

  Eligibility

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

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
  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

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

Locations
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         
Sub-Investigator: Bret Goodpaster, PhD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
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
  More Information

No publications provided

Responsible Party: Kara Hughan, Instructor 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: January 30, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 28, 2014