Effects of Nitric Oxide and Nitroglycerin in Patients With Sickle Cell Anemia

NCT00001716 | Completed Phase 2

• 2 other identifiers: 98012998-CC-0129
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Sickle cell anemia is the most common genetic disease affecting African-Americans. About 1 in every 1000 African-Americans has the disease and 1 in every 12 carry the genes that could be passed on to their children. People with sickle cell anemia have abnormal hemoglobin, the molecules responsible for carrying oxygen in the blood. The abnormal hemoglobin can cause damage to the red blood cells. The damaged red blood cell may then stick in the blood vessels and cause pain and injury to organs. Some of the complications caused by the sticking of blood cells are called acute pain crisis and acute chest syndrome (ACS). Nitric oxide (NO) is a gas that has been proposed as a possible therapy for the ACS complication of sickle cell anemia. Studies have shown that NO may favorably affect sickle cell hemoglobin molecules, thereby improving blood flow through small vessels. This study is designed to evaluate the effects of NO, when taken in combination with a drug called nitroglycerin on patients with sickle cell anemia and normal volunteers. The effects of these two drugs only last while the patient is receiving them. Researchers hope the information learned from this study will help to develop new therapies for sickle cell anemia.

Conditions

Chest Pain; Sickle Cell Anemia

Keywords

Hemoglobin; P50; Microvascular; Perfusion; Magnetic Resonance Imaging; Sickle Cell Anemia

Interventions

Nitric Oxide DRUG

Nitroglycerin DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females 18 to 65 years of age.
• Diagnosis of sickle cell disease (electrophoretic documentation of SS homozygosity is required) or identification as a normal volunteer.
• Hematocrit greater than 18% (with an absolute reticulocyte count greater than 100,000/ml).
• Hematocrit 18-21% (with an absolute reticulocyte count greater than 100,000/ml): Only 100 ml of blood may be drawn. The study subject may be re-entered in the study after four weeks (with repeat full screening labs).

You may not qualify if:

• Clinically unstable sickle cell anemia defined by the following:
• Having greater than two acute pain crises in the last two months; on hydroxyurea or butyrate therapy any time in the last 12 months; or blood transfusion within last three months, or % hemoglobin A greater than 20%.
• Age less than 18 years or greater than 65 years.
• Current pregnancy or lactation.
• Inability to exercise the anterior tibialis muscle.
• Active cigarette smoker-defined as the inhalation of smoke from any tobacco product in the last one month.
• Medical conditions: diabetes mellitus; coronary artery disease; peripheral vascular disease; migraine headaches in the last 12 months; history of previous CVA or stroke; or creatinine greater than 1.0 mg/dL.
• Hematocrit less than or equal to 18 percent: will not be eligible for the study; may return for evaluation at a later date.
• No aspirin or non-steroidal anti-inflammatory drugs (no NSAIDS and caffeine the day of the study.) Patients on opiates and acetaminophen will not be excluded.
• Patients taking Viagra will be excluded from the study.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

Warren G. Magnuson Clinical Center (CC)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997 Sep 11;337(11):762-9. doi: 10.1056/NEJM199709113371107. No abstract available.

  PMID: 9287233 BACKGROUND

• Head CA, Brugnara C, Martinez-Ruiz R, Kacmarek RM, Bridges KR, Kuter D, Bloch KD, Zapol WM. Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo. J Clin Invest. 1997 Sep 1;100(5):1193-8. doi: 10.1172/JCI119631.

  PMID: 9276736 BACKGROUND

• Gow AJ, Stamler JS. Reactions between nitric oxide and haemoglobin under physiological conditions. Nature. 1998 Jan 8;391(6663):169-73. doi: 10.1038/34402.

  PMID: 9428761 BACKGROUND

MeSH Terms

Conditions

Chest Pain; Anemia, Sickle Cell

Interventions

Nitric Oxide; Nitroglycerin

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals; Nitro Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: July 1, 1998
• Study Completion: July 1, 2003
• Last Updated: March 4, 2008

Record last verified: 2003-07

Locations

US (1)