Effect of Nitrite on Exercise Physiology and Metabolism

NCT00105222 | Terminated Phase 1

• 2 other identifiers: 05011405-H-0114
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine how nitrite infusions affect exercise tolerance (how much a person can exercise before having to stop). Exercise ability is limited by how fast oxygen can be delivered to the body and how fast the body can produce energy. Both of these processes are affected by nitric oxide (NO), a gas produced by cells that line blood vessels. NO is important in regulating blood vessel dilation, and consequently, blood flow. Nitrite may act as a storehouse for nitric oxide and be able to improve exercise tolerance. Healthy normal volunteers between 21 and 45 years of age who can use an exercise bicycle may be eligible for this study. Candidates are screened with a medical history, physical examination, electrocardiogram, breathing tests, blood tests, and a pregnancy test for women who are able to bear children. Pregnant women are excluded from the study. The screening session includes practice exercise on the bicycle. Participants exercise on a stationery exercise bicycle for about 30 minutes on each of two study days. During the test, they breathe in and out of a mouthpiece that allows inhaled and exhaled respiratory gases to be measured. Before subjects begin to exercise, a small tube is placed in the artery of their forearm inside the elbow. A longer tube called a central line is placed in a deeper vein in the neck after the area has been numbed. A thinner tube, called a pulmonary artery catheter, is placed through the central line and advanced into the chambers of the heart, through the heart valve, and into the lung artery. This catheter measures various pressures directly in the heart and lungs. Blood samples are drawn through the catheter also, to avoid the need for multiple needle sticks. Another tube is placed in the vein of the other arm to deliver medications. Thirty minutes after all the tubes are placed, a blood sample is drawn for baseline measurements. Then, either saline (sterile salt water) or nitrite is injected into the tube in the arm vein. Thirty minutes after the injection, the subject starts exercising on the bicycle. The work setting on the bicycle is increased every minute, and the subject pedals until he or she is too tired to continue. During the test, a small blood sample is collected every 2 minutes. Heart rate, blood pressure, and heart rhythms are continuously monitored. After the test on the first day, participants are admitted to the hospital to rest for the remainder of the afternoon and evening. The tubes are kept in place for the following morning, when the procedure is repeated exactly as before, except that subjects who received saline the first day are given nitrite the second day, and vice versa. ...

Conditions

Healthy; Healthy Volunteer; HV

Keywords

Cycle Ergometer; Exercise Physiology; Nitric Oxide; Sodium Nitrite; Healthy Volunteers; Normal Volunteer; Healthy Volunteer; HV

Interventions

Sodium Nitrite DRUG

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be 21-45 years of age.
• Subject must be in good health and able to perform cycle ergometry for the length of the study.
• 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 of cardiac, pulmonary, peripheral vascular, or mitochondrial disease.
• Subjects with abnormal EKG other than sinus bradycardia.
• 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 any physical condition (for example, knee problems) that may impair their performance during exercise testing.
• Subjects who have a history of smoking within one year.
• Subjects with anemia (defined as hemoglobin less than 10 g/dL).
• 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 G6PD deficiency.
• Subjects with a baseline methemoglobin level greater than 1%.
• Lactating females who are breastfeeding, 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, herbal preparations, nutriceuticals or other alternative therapies for at least one month prior to study and will not be allowed to take aspirin or NSAIDs for one week prior to study.
• Subjects with a blood pressure of less than 100/70 mmHg on the study day will be excluded from the protocol.

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)

• Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol. 1996 Nov;271(5 Pt 1):C1424-37. doi: 10.1152/ajpcell.1996.271.5.C1424.

  PMID: 8944624 BACKGROUND

• 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

MeSH Terms

Interventions

Sodium Nitrite

Intervention Hierarchy (Ancestors)

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

Study Officials

• Gregory J Kato, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 9, 2005
• First Posted: March 10, 2005
• Study Start: March 8, 2005
• Primary Completion: August 16, 2013
• Study Completion: August 16, 2013
• Last Updated: July 5, 2018

Record last verified: 2013-08-16

Locations

US (1)