Dipyridamole/Magnesium To Improve Sickle Cell Hydration
The purpose of this study is to determine the benefits as well as side effects of giving drugs called dipyridamole and magnesium to patients with sickle cell anemia (SCA).
Anemia, Sickle Cell
Drug: oral dipyridamole, oral magnesium, or a combination of both
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
|Official Title:||Dipyridamole/Magnesium To Improve Sickle Cell Hydration|
- To assess effects on red cell hydration.
- To assess effects on red cell survival. Measurements will be performed before and after treatment.
- To monitor side effects of each treatment arm.
- To evaluate clinical outcomes during each phase of the study.
|Study Start Date:||May 2005|
Vaso-occlusive episodes are the most common problem experienced by patients with SCA and the most frequent reason for hospital admissions as well as visits to the clinic and emergency department. Many cellular, humoral, and vascular factors influence the initiation and propagation of vaso-occlusion by sickle cells. Among these is the tendency of sickle cells (SS RBC) to become dehydrated with accompanying increase in the hemoglobin (Hb) concentration. Since sickle hemoglobin (Hb S) concentration controls the rate of polymerization, cellular dehydration plays a key role in sickle cell pathology.
Two separate but interdependent cation transport mechanisms affect sickle cell hydration, the first involving abnormal KCl cotransport (KCC), and the second a sickle-induced (SI) passive leak which permits the influx of calcium ions (Ca++) that activates the Gardos pathway, a Ca++-dependent K channel. Early investigations aimed at inhibiting KCC with magnesium (Mg) and the Gardos pathway with clotrimazole met with partial success. We have recently shown in vitro that dipyridamole also inhibits the SI pathway. Strategies designed to block the formation of these dense, dehydrated cells would offer important therapeutic options that might decrease the number and severity of the vaso-occlusive episodes in patients. Drawing on the information gained from two decades of research on cation transport in SS RBC, including the unique discovery made at this Center that dipyridamole inhibits the SI cation leak, we now propose a study of combined therapy using two transport inhibitors aimed at reducing SS RBC dehydration.
|United States, Michigan|
|Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|University of Cincinnati|
|Cincinnati, Ohio, United States, 45219|
|Principal Investigator:||Karen Kalinyak, MD||Children's Hospital Medical Center, Cincinnati|