Nitrite Infusion in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00103025
First received: February 5, 2005
Last updated: May 11, 2011
Last verified: May 2011
  Purpose

This study will determine the dose of sodium nitrite that can safely be used to prevent constriction, or tightening, of the arteries. Narrowed arteries in the brain can cause stroke. Animal studies show that nitrite injections improve blood flow and that injections over long periods of time prevent damage to the arteries in the brain; however, there is no information on the effects of prolonged nitrite infusion in humans. This study will establish the safe dose and side effects of nitrite infusion in humans.

Healthy normal volunteers between 21 and 60 years of age may be eligible for this study. Candidates are screened for high or low blood pressure, aspirin use, pregnancy, and blood levels of nitrite and methemoglobin (a substance that temporarily and slightly lowers the oxygen carried in the red blood cells). Pregnant women are excluded from the study.

Participants are admitted to the Clinical Center for 16 1/4 days, the first 2 days in the hospital's intensive care unit (ICU). Upon admission they provide a medical history, have physical and cardiovascular examinations, and blood tests. For the infusion procedure, a catheter (thin plastic tube) is inserted into an artery in the wrist or the crease of the elbow to measure blood pressure, and catheters are placed in a vein in each arm for administering the nitrite and withdrawing blood samples.

In the morning of day 1, after initial blood pressure and heart rate measurements are taken and a blood sample is drawn, a saline (salt water) infusion is started. Blood pressure and heart rate are monitored every 30 minutes for 6 hours, then every hour for 6 hours, then every 2 hours for 12 hours. Blood samples are collected every 4 hours for 24 hours. On day 2, the sodium nitrite infusion begins. Blood pressure and methemoglobin are monitored every 10 minutes for the first 2 hours. If blood pressure remains stable, the frequency of measurements is decreased to every 30 minutes for 4 hours, then every 1 hour for the next 6 hours, and then every 4 hours for 12 hours. If the pressure continues to remain stable, monitoring continues every 8 hours for the rest of the study. Blood is drawn periodically from the catheter to determine the amount of nitrite and methemoglobin in the body, with decreasing frequency from several times during the first hour of the infusion to every 24 hours. After the first 24 to 48 hours of the nitrite infusion, participants are transferred from the ICU to a general nursing unit fo...


Condition Intervention Phase
Healthy
Drug: Sodium Nitrite
Drug: Sodium Nitrite Injection
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of the Mechanism of NO Formation and Pharmacokinetics of Long-Term Intravenous Nitrite Infusion in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 12
Study Start Date: February 2005
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Sodium Nitrite
    N/A
    Drug: Sodium Nitrite Injection
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Subjects must be 21-60 years of age.

Subjects 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 and agree to participate in assessment of menstrual cycle duration before, during, and after infusion.

Subjects must be willing to temporarily stop any medications (except oral contraception), vitamin supplements, herbal medicines.

Subjects will have hemoglobin levels above 11.1 g/dL.

EXCLUSION CRITERIA:

Subjects with a history or evidence of present or past hypertension (blood pressure greater than 140/90 mmHg), hypercholesterolemia (LDL cholesterol greater than 130 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.

Subjects with red blood cell G6PD deficiency (levels below the lower limits of normal).

Subjects with a history of reaction to a medication or other substance characterized by dyspnea and cyanosis.

Subjects with a baseline methemoglobin level greater than 1%.

Pregnant women, since nitrite may cross the placenta; nitrite effect on fetus is unknown and mother's methemoglobinemia may be dangerous to the fetus.

Breast-feeding females, since nitrite crosses into breast milk and could cause methemoglobinemia in the infant.

Subjects with a blood pressure of less than 100/70 mmHg on the study day.

Subjects treated with nitrates (e.g. nitroglycerin).

  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: NCT00103025

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Russell R. Lonser, M.D./National Institute of Neurological Disorders and Stroke, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00103025     History of Changes
Other Study ID Numbers: 050075, 05-N-0075
Study First Received: February 5, 2005
Last Updated: May 11, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Vasodilation
Hypotension
Hypertension
EDRF
Methemoglobinemia
Healthy Volunteer
HV

ClinicalTrials.gov processed this record on October 16, 2014