Nitric Oxide to Improve Blood Flow in Sickle Cell Disease
Maneno muhimu
Kikemikali
Maelezo
Sickle cell anemia is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Acute pain crisis and acute chest syndrome are common complications of sickle cell anemia. Inhaled nitric oxide (NO) has been proposed as a possible therapy for the acute chest syndrome. Anecdotally, NO has been described to rapidly improve the hypoxemia and the clinical course of the acute chest syndrome. Furthermore, a number of recent studies have suggested that NO may have a favorable impact on sickle red cells at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia. This clinical trial is designed to test the hypotheses that 1) individuals with sickle cell anemia have endothelial dysfunction with reduced local synthesis and release of NO, that may reduce regional perfusion at rest and impair the vasodilator response to stress, and 2) during NO inhalation, delivery of NO bound to hemoglobin will be enhanced and will improve these abnormalities in regional vascular perfusion. Studies will be performed on untreated sickle cell anemia patients and on patients managed with chronic hydroxyurea therapy. Demonstration of improved regional perfusion with NO therapy could have significant implications for patient management during acute pain crisis and the acute chest syndrome.
Tarehe
Imethibitishwa Mwisho: | 12/31/2002 |
Iliyowasilishwa Kwanza: | 01/31/2001 |
Uandikishaji uliokadiriwa Uliwasilishwa: | 01/31/2001 |
Iliyotumwa Kwanza: | 02/01/2001 |
Sasisho la Mwisho Liliwasilishwa: | 03/02/2008 |
Sasisho la Mwisho Lilichapishwa: | 03/03/2008 |
Tarehe halisi ya kuanza kwa masomo: | 12/31/2000 |
Tarehe ya Kukamilisha Utafiti: | 12/31/2002 |
Hali au ugonjwa
Uingiliaji / matibabu
Drug: L-NMMA
Drug: Acetylcholine
Awamu
Vigezo vya Kustahiki
Jinsia Inastahiki Kujifunza | All |
Hupokea Wajitolea wa Afya | Ndio |
Vigezo | INCLUSION CRITERIA Males or females 18 to 65 years of age are eligible. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S beta(0) thallassemia genotype is required). Hematocrit greater than 18 percent (with an absolute reticulocyte count greater than 100,000/ml). Volunteer subjects taking hydroxyurea must have been on therapy with the drug for at least four months. Volunteer subjects not taking hydroxyurea must have been off of therapy with the drug for at least 4 months. EXCLUSION CRITERIA Clinically unstable sickle cell anemia defined as having an acute pain crisis within the last week. Age less than 18 years or greater than 65 years. Current pregnancy or lactation. Conditions that may independently affect endothelial function: 1. Diabetes mellitus or Fasting blood sugar greater than 120 mg/dL 2. Cigarette smoking within two years 3. Hypertension (diastolic blood pressure greater than 90 mmHg) 4. Lipid abnormalities (LDL cholesterol greater than 160 mg/dL, HDL cholesterol less than 30 mg/dL, triglycerides greater than 500 mg/dL) 5. Creatinine greater than 1.0 mg/dL Hematocrit less than or equal to 18 percent: however, patients may return for evaluation at a later date. No aspirin or non-steroidal antiinflammatory drugs (NSAIDs for one week and caffeine the day of the study). Patients on opiates and acetaminophen will not be excluded. Patients taking sildenafil (Viagra) will be excluded from the study. Recent transfusion (last 4 weeks) or hemoglobin A greater than 5 percent. |