Nitric Oxide to Improve Blood Flow in Sickle Cell Disease
|ClinicalTrials.gov Identifier: NCT00009581|
Recruitment Status : Completed
First Posted : February 2, 2001
Last Update Posted : March 4, 2008
Nitric oxide is important in regulating blood vessel dilation, and consequently, blood flow. This gas is continuously produced by cells that line the blood vessels. It is also transported from the lungs by hemoglobin in red blood cells. This study will examine how this gas regulates blood vessels and blood flow in people with sickle cell anemia. It will also look at a possible benefit of using certain genetic information to compare the white blood cells of people with sickle cell anemia to those without the disease.
Patients with sickle cell anemia and healthy normal volunteers 18 to 65 years of age may be eligible for this study. Candidates will be screened with a medical history, cardiovascular physical examination, electrocardiogram and routine blood tests. Participation of volunteers without sickle cell anemia will be limited to a single blood draw for genetic study. Sickle cell disease patients will undergo the following procedures:
Patients will lie in a reclining chair during the study. After administration of a local anesthetic, small tubes will be inserted through a needle into the artery and vein of the patient's forearm. These are used to measure blood pressure and draw blood samples during the study. Forearm blood flow will be measured using pressure cuffs placed on the wrist and upper arm, and a strain gauge (a rubber band device) placed around the forearm. When the cuffs are inflated, blood flows into the arm, stretching the strain gauge, and the flow measurement is recorded. A small lamp will be positioned over the hand. Light reflected back from the hand provides information about nitric oxide and hemoglobin in the blood of the skin. A squeezing device called a dynamometer will be used to measure handgrip strength.
Baseline blood flow, nitric oxide, hemoglobin, and handgrip will be measured after an infusion of glucose (sugar) and water. These measurements will be repeated at various times before, during and after administration of small doses of the following drugs:
- Sodium nitroprusside - causes blood vessels to dilate and increases blood flow to the heart
- Acetylcholine - causes blood vessels to dilate and slows heart rate
- LNMMA - decreases blood flow by blocking the production of nitric oxide
There will be a 20- to 30-minute rest period between injections of the different drugs.
When the above tests are completed, the patient will breathe a mixture of room air and nitric oxide for 1 hour through a facemask placed over the face, after which forearm blood flow and light reflected from the hand will be measured. Then the patient will do the handgrip exercise for 5 minutes, after which blood flow and hand lamp measurements will be taken. After a 20-minute rest period (with continued breathing of room air/nitric oxide), L-NMMA will be infused again. The handgrip exercise, blood flow and hand lamp measurements will be repeated. The face mask will then be removed, and the tubes will be removed 20 minutes later.
Blood samples will be collected at various times during the 5- to 6-hour study through the tubes in the arm. Some of the blood will be used to look at genes that make proteins involved in cell-to-cell communication, inflammation, and in making red and white blood cells stick to the lining of blood vessels.
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Anemia||Drug: L-NMMA Drug: Acetylcholine||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||65 participants|
|Official Title:||Targeted Delivery of Nitric Oxide by Hemoglobin to Improve Regional Blood Flow in Sickle Cell Disease|
|Study Start Date :||January 2001|
|Estimated Study Completion Date :||January 2003|
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00009581
|United States, Maryland|
|Warren G. Magnuson Clinical Center (CC)|
|Bethesda, Maryland, United States, 20892|