Study Detail

Study ID 1025
Name Comprehensive Sickle Cell Centers' (CSCC) -HU-Mg
Contact Email
Acronym CSCC-HU-Mg
Period 2007 - 2009
Design Clinical Trial
Study PI Winfred Wang
Institution RTI International
Funding Agency NHLBI
Overview Hemoglobin (Hb) SC disease is characterized by dense red blood cells, but treatment approachesaimed at its pathophysiology have been limited in scope. Furthermore, combination drug therapy in sickle celldisease has not been adequately tested. We will examine two oral therapies, hydroxyurea and magnesium, givenby themselves and in combination and compare them to placebo in a double-blinded Phase II study to determinetheir efficacy in reducing red cell density in Hemoglobin SC in children and adults. We will also examine theireffects on other red cell characteristics and on the frequency of clinical vaso-occlusive events. To accomplishthis, 188 subjects will be assigned randomly to one of four treatment groups (see below) and followed for oneyear after beginning treatment.
Focus Areas 1. To compare the effectiveness of hydroxyurea (HU) alone, magnesium pidolate (Mg) alone,and hydroxyurea + Mg in combination, and placebo in reducing the density of HbSC erythrocytes.
2. To examine the effect of the individual and combination treatments on:• hematologic parameters and Hb F levels in HbSC disease;• other biologic measures of erythrocyte activity and red cell-endothelial interactions in HbSC disease;• and prevention of vaso-occlusive episodes in HbSC disease.Additionally, we will examine the safety of HU + Mg in combination.
Outcomes 1. The change-from-baseline density of hemoglobin SC red cells (percent of RBCs with densitygreater than 41 g/dL) measured 2 months after initiation of treatment.
2. Change-from-baseline in:• Standard hematologic parameters [hemoglobin level, mean cell volume (MCV), reticulocyte count, whiteblood cell count, platelet count, absolute neutrophil count (ANC)].• Hemoglobin S, C, and F levels.• Red cell metabolic studies: K-Cl co-transport activity, Gardos channel activity, Na-Mg exchanger activity,red cell cation content, intracellular Mg.• Plasma total Mg and ionized Mg (iMg) levels.• Adhesion studies to laminin, thrombospondin, and endothelial cells; expression of red cell receptors andphosphatidylserine; adhesive response to epinephrine.Also the frequency of clinical vaso-occlusive events (pain events, acute chest syndrome).
Data Location RTI International
Biospecimen Available Blood; DNA; Plasma; Serum; Urine;
Data Consent Consent includes statement regarding confidentiality of records. Deidentified data may be used for continuing research.
Biospecimen Consent Samples collected during the study will be deidentified; all samples will be destroyed at the end of the study.
Contact Consent NA
Genomic Data Yes
Age Range 5-99
No. Participants 44
Inclusion Criteria 1. Diagnosis of HbSC disease
2. Hemoglobin level between 8 and 12.5 g/dL
3. At least one vaso-occlusive event (e.g., pain, acute chest syndrome) in the 12 months prior to study entry. An episode of pain is defined as the occurrence of pain in the extremities, back, abdomen, chest, or head that lasts at least 2 hours; requires a visit to a hospital, emergency room, clinic, or provider's office; and is not explained except by SCD. Acute chest syndrome is defined as a new pulmonary infiltrate on a chest x-ray associated with a fever (greater than 38.5° C), tachypnea, wheezing, cough, or chest pain.
4. Regular compliance with comprehensive care
5. In a steady disease state and not experiencing an acute complication of SCD (i.e., no hospitalization, pain event, or episode of acute chest syndrome within the 1 month prior to study entry)
Exclusion Criteria 1. Previous transfusion with remaining hemoglobin A greater than 10%
2. Previous treatment with hydroxyurea within the last 3 months
3. Previous treatment with magnesium within the 3 months prior to study entry (including vitamins containing magnesium)
4. Poor compliance with previous treatment regimens
5. Liver dysfunction (SGPT greater than twice the upper limit of normal) within the 1 month prior to study entry
6. Kidney dysfunction (creatinine greater than or equal to 1.0 mg/dL for participants less than 18 years of age; greater than or equal to 1.2 mg/dL for participants 18 years of age or older) within the 1 month prior to study entry
7. Pregnant
8. Ten or more hospital admissions for pain in the 12 months prior to study entry
9. Daily use of narcotics
10. Treatment with any investigational drug in the 3 months prior to study entry
11. Less than 3% red blood cells with density greater than 41 g/dL (as measured by the ADVIA 120 system)
12. Positive HIV test
13. Other long-term illness or disorder other than SCD that could adversely affect performance in the study (e.g., tuberculosis)
Study Documentation
  Select All
  Select All

Back to Study List