Nitrite Infusion Studies

NCT00102271 | Completed Phase 1

• 2 other identifiers: 05008805-H-0088
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine 1) how nitrite (a natural blood substance that relaxes blood vessels) increases blood flow and lowers blood pressure, and 2) how to increase the effects of nitrite on blood pressure. Healthy volunteers between 21 and 40 years of age may be eligible for this study. They must be non-smokers and have no history of high blood pressure, high cholesterol, or diabetes. Candidates are screened with a medical history, physical examination, electrocardiogram, and blood tests. This study is either done in the NIH Clinical Center intensive care unit or on the general clinical ward. Participants are enrolled in Part A of the study. After completion of Part A participants will be enrolled in Part B of the study. Part A: Participants lie in a reclining chair during the study. Small catheters (plastic tubes) are inserted into an artery and vein in the forearm. Another tube is placed in the vein of the opposite arm. Blood pressure cuffs are placed around the upper arm and wrist, and a strain gauge (a rubber band-like device) is placed around the forearm. This device helps us to measure blood flow through the arm. When the blood pressure cuffs are inflated, blood flows into the forearm, stretching the strain gauge at a rate proportional to the blood flow. Pressure cuffs and a strain gauge are also placed on the other arm. After 20 minutes, blood pressure and blood flow are measured in both forearms. Then blood is drawn from the tube in the right vein to measure blood counts, proteins, and other chemicals. Participants then are given small doses of either saline, ascorbic acid, or a medicine called oxypurinol, a form of a drug that is often taken to prevent gout. After 30 minutes, sodium nitrite is injected in increasing doses into the artery for 30 minutes. Blood flow is measured and blood is drawn every 5 minutes during the infusion. At the end of the 30 minutes, blood is drawn from the vein every 30 minutes for 3 hours. After 3 hours, sodium nitrite infusions are restarted for 2 hours and blood flow is measured and samples collected every 30 minutes during this period. Part B: Participants lie in a reclining chair during the study. A small catheter (plastic tube) is placed in the artery of the left forearm to draw blood samples. A larger catheter called a central line is placed in a deeper vein in the neck. Another tube is advanced through the central line into the chambers of the heart, through the heart valve, and into the lung artery to measure pressures in the heart and lungs. Blood is drawn after 30 minutes to obtain baseline measurements. Then saline (sterile salt water) is put into the tube in the lung artery. Blood pressure cuffs are placed around the upper arm and wrist, and a strain gauge (a rubber band-like device) is placed around the forearm, which helps us to measure flow through the arm. When the cuffs are inflated, blood flows into the forearm, stretching the strain gauge at a rate proportional to the blood flow. Pressure cuffs and a strain gauge are also placed on the other arm. After 20 minutes, blood pressure and blood flow are measured in the forearm and blood samples are drawn from the tube in the left artery to measure blood counts, proteins, and other chemicals. Subjects then breathe a mixture of oxygen and nitrogen through a facemask for 30 minutes, then room air for 30 minutes, and then the oxygen and nitrogen mixture for another 30 minutes. While breathing the mixture the second time, sodium nitrite is injected through the tube in the artery in three increasing doses for 5 minutes each. Every 5 minutes during the infusion blood is drawn from the tubes in the neck. Forearm blood flow is also measured every 5 minutes. After 30 minutes, the subject breathes room air for 3 hours and 15 minutes and then the sodium nitrite is injected again in three increasing doses for 5 minutes each. Every 5 minutes during the infusion blood is taken from the tube in the neck and forearm blood flow is measured

Conditions

Healthy

Keywords

Sodium Nitrite; Oxypurinol; Ascorbic Acid; Hypoxic Gas; Forearm Blood Flow; Healthy Volunteer; HV

Interventions

Oxypurinol DRUG

Sodium Nitrite DRUG

Eligibility Criteria

• Age: 21 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be 21-40 years of age.
• Subject must be in good health.
• Subjects must provide informed, written consent for participation in this study.
• Female subjects of childbearing age must have a negative pregnancy test.

You may not qualify if:

• Subjects with a history or evidence of present or past hypertension (blood pressure greater than 140/90 mmHg), hypercholesterolemia (LDL cholesterol greater than 160 mg/dL), or diabetes mellitus (fasting blood glucose greater than 126 mg/dL)
• Subjects who have a history of smoking within two years
• Subjects who have a history of cardiovascular disease, peripheral vascular disease, coagulopathy, or any other disease predisposing to vasculitis or Raynaud's phenomenon.
• Individuals with a future cardiovascular risk greater than 1 % in the next 10 years will be excluded from the study. Risk will be calculated using the Framingham risk calculator published on the web site: http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof.
• Subjects with red blood cell G6PD deficiency (levels below the lower limits of normal).
• Subjects with known cytochrome B5 deficiency will not participate in this study.
• Subjects with a history of reaction to a medication or other substance characterized by dyspnea and cyanosis will not participate in this study.
• Subjects with a baseline methemoglobin level greater than 1.9% will not receive nitrite infusions.
• Lactating females will not participate since nitrite crosses into breast milk and could cause methemoglobinemia in the infant.
• No volunteer subject will be allowed to take any medication (oral contraceptive agents are allowed), vitamin supplements that contain arginine, herbal preparations, nutriceuticals or other "alternative therapies" for at least one month prior to study and will not be allowed to take aspirin for one week prior to study
• Subjects with a blood pressure of less than 90/60 mmHg or a MAP (mean arterial blood pressure) of less than 70 on the study day will be excluded from the protocol.
• Due to exposure of high doses of ascorbic acid in this protocol calcium oxalate stone formers, patients on dialysis or with serious kidney disease, and patients with hemochromatosis and other iron overload diseases will be excluded.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Boucher JL, Moali C, Tenu JP. Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for L-arginine utilization. Cell Mol Life Sci. 1999 Jul;55(8-9):1015-28. doi: 10.1007/s000180050352.

  PMID: 10484661 BACKGROUND

• Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373-6. doi: 10.1038/288373a0.

  PMID: 6253831 BACKGROUND

• Ignarro LJ. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol. 1990;30:535-60. doi: 10.1146/annurev.pa.30.040190.002535. No abstract available.

  PMID: 2188578 BACKGROUND

MeSH Terms

Interventions

Oxypurinol; Sodium Nitrite

Intervention Hierarchy (Ancestors)

Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Nitrites; Nitrous Acid; Nitrogen Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 25, 2005
• First Posted: January 26, 2005
• Study Start: January 19, 2005
• Study Completion: April 12, 2011
• Last Updated: July 2, 2017

Record last verified: 2011-04-12

Locations

US (1)