Effect of Hydroxyurea on the Level of Ineffective Erythropoiesis, Transfusion Requirement, and Fetal Hemoglobin Synthesis in Patients With Beta-Thalassemia-Intermedia
Hydroxyurea
Anemia+7
+ Anemia, Hemolytic
+ Anemia, Hemolytic, Congenital
Treatment Study
Summary
Study start date: December 1, 1999
Actual date on which the first participant was enrolled.Individuals with homozygous beta thalassemia are either severely anemic or dependent on blood transfusion to sustain life. Deficient synthesis of the beta chain leads to imbalanced chain synthesis with an excess of alpha globin. This alpha globin precipitates, causing ineffective erythropoiesis and shortened red cell survival. Hydroxyurea is a cell-cycle specific agent that blocks DNA synthesis by inhibiting ribonuclease reductase, the enzyme that converts ribonucleotides to deoxyribonucleotides. Administration of hydroxyurea to primates and more than 300 patients with sickle cell anemia has been frequently, but not invariably associated with a substantial increase in synthesis of gamma globin. In patients with homozygous beta-thalassemia, enhanced gamma globin synthesis could partially compensate for the deficient synthesis of beta globin rendering chain synthesis more balanced and reducing the relative excess of alpha chains. The purpose of this protocol is to test the hypothesis that chronic daily low dose administration of hydroxyurea will enhance gamma globin synthesis, increase red cell production and partially or substantially correct the anemia in patients with homozygous beta-thalassemia. The effect of treatment will be monitored by serial determination of the hemoglobin and hematocrit. The relationship between response to therapy and the specific beta-globin mutation(s) will also be analyzed. This study will therefore examine a cohort of patients not previously treated with hydroxyurea.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.100 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Beta-Thalassemia Intermedia patients. Steady-state Hb values greater than 6.5gm/dl (unrelated to transfusion) Males and females. Patients greater than 15 years of age. Patients who are transfusion-requiring but not dependent will be offered the opportunity to enroll. Stable renal and hepatic function Willingness to use appropriate birth control measures. Ability to give informed consent. No beta-thalassemia major. No blood transfusion requirement greater than 1 unit every 2 months over the last 12 months. No patients with WBC less than 4000/micrograms. No one with a platelet count less than 150,000/micrograms. No evidence of active viral infective, including viral hepatitis. No abnormal liver function test (ALT or AST greater than 2.5 x normal). No abnormal renal function test (creatinine greater 1.5 mg/dl). No HIV positive blood test.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Bethesda, United StatesOpen National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in Google Maps