Oral Nitrite in Adults With Metabolic Syndrome and Hypertension

NCT01681810 | Completed Phase 2 Results

• 1 other identifier: PRO11030131
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Syndrome; Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in Insulin Stimulated Glucose Disposal Over 12 Week Study Period

  Change in insulin stimulated glucose disposal was assessed during the 4-hour hyperinsulinemic euglycemic clamp at end of the 12 weeks and was compared to baseline (pre-nitrite). Insulin stimulated glucose disposal (mg/min) was calculated in the final 20 minutes of the 4-hour clamp at steady state and expressed as mg per kg lean body mass (as measured by DEXA) per minute. HumuLIN R regular insulin was infused at a rate of 40 microUnits/m2/min. A non-radioactive glucose isotope dilution (Isotec, Inc) was delivered as a primed, then constant infusion of the 98+% enriched stable isotope of D-glucose \[6,6-D2\] (0.22 umol x kg-1, 17.6 umol x kg-1 prime). Plasma glucose was clamped between 85-95 mg/dL with a variable infusion of 20% dextrose in water. The rate of dextrose infusion was adjusted based on arterialized plasma glucose measurements obtained every 5 minutes.

  measured at 0 (baseline) and at 12 weeks

Secondary Outcomes (4)

• Peak Change in Systolic Blood Pressure Over 12 Week Study Period

  measured at 0 (baseline) and bi-weekly over 12 weeks

• Peak Change in Diastolic Blood Pressure Over 12 Week Study Period

  measured at 0 (baseline) and bi-weekly over 12 weeks

• Peak Change in Mean Arterial Pressure Over 12 Week Study Period

  measured at 0 (baseline) and bi-weekly over 12 weeks

• Peak Change in Methemoglobin Over 12 Week Study Period

  measured at 0 (baseline) and bi-weekly over 12 weeks

Study Arms (1)

14Nitrogen sodium nitrite

EXPERIMENTAL

sodium nitrite 40 mg three times a day for 12 weeks

Drug: 14Nitrogen Sodium Nitrite

Interventions

14Nitrogen Sodium Nitrite DRUG

oral formulation of sodium nitrite 40 mg three times a day for 12 weeks

Also known as: sodium nitrite

14Nitrogen sodium nitrite

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60 years
• Body mass index (BMI) greater than or equal to 30 kg/m\^2
• Hypertension: defined as systolic blood pressure (SBP) greater than or equal to 130 and/or diastolic blood pressure (DBP) greater than or equal to 85 mm Hg
• Waist circumference: greater than 102 cm in men, greater than 88 cm in women

You may not qualify if:

• 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 \[oral contraceptive pill (OCP), intrauterine device (IUD), DepoProvera\]
• Current use of greater than or equal to 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) greater than 8 milli-International unit/mL
• Smoker
• Anemia (central lab hemoglobin less than 11g/dL)

Sponsors & Collaborators

• Gladwin, Mark, MD: lead

Study Sites (1)

Montefiore Hospital of University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Hughan KS, Levine A, Helbling N, Anthony S, DeLany JP, Stefanovic-Racic M, Goodpaster BH, Gladwin MT. Effects of Oral Sodium Nitrite on Blood Pressure, Insulin Sensitivity, and Intima-Media Arterial Thickening in Adults With Hypertension and Metabolic Syndrome. Hypertension. 2020 Sep;76(3):866-874. doi: 10.1161/HYPERTENSIONAHA.120.14930. Epub 2020 Aug 3.

  PMID: 32755471 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome; Hypertension

Interventions

Sodium Nitrite

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Nitrites; Nitrous Acid; Nitrogen Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

The pre-drug clamp isotope data for 1 subject (used to determine insulin stimulated glucose disposal) was uninterpretable, despite repeating the mass spectrometry assay. Subject's isotope data was removed from analysis (n=19 analysis sample size).

Results Point of Contact

• Title: Dr. Kara Hughan
• Organization: University of Pittsburgh

kara.hughan@chp.edu

4126925173

Study Officials

• Kara S Hughan, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Mark Gladwin, MD

  University of Pittsburgh

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: July 3, 2012
• First Posted: September 10, 2012
• Study Start: October 1, 2012
• Primary Completion: February 8, 2018
• Study Completion: March 8, 2018
• Last Updated: April 16, 2019
• Results First Posted: April 16, 2019

Record last verified: 2019-03

Locations

US (1)