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Dipyridamole/Magnesium To Improve Sickle Cell Hydration

Phase 2
12 Years
Not Enrolling
Anemia, Sickle Cell

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Trial Information

Dipyridamole/Magnesium To Improve Sickle Cell Hydration

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.

Inclusion Criteria:

- Patients with homozygous sickle cell (Hb SS) confirmed by hemoglobin electrophoresis

- Patients with adequate cardiac, renal, and liver function

- Patients with baseline fetal hemoglobin (Hb F) level of 10% or less

- Patients with at least 6% dense cells or higher at initial screening visit

- Patients with no history of coronary heart disease

- Patients with normal baseline ECG

- Patients with no history of hypotension or hypotensive episodes

Exclusion Criteria:

- Patients who are pregnant, trying to become pregnant, or breast feeding

- Patients who are on a chronic transfusion program

- Patients who are unable to take oral medications

- Patients who have significant cardiac, renal, or liver dysfunction

- Patients who are on hydroxyurea

- Patients who have a fetal hemoglobin (Hgb F) level of greater than 10%, or have less
than 6% dense cell on initial screen

- Patients who are taking a supplement which contains magnesium

- Patients who are taking aspirin, ibuprofen on a daily basis, or anti-coagulant such
as Coumadin on a daily basis

- Patients who have a known underlying coagulopathy (acquired or congenital) or have
prolonged PT or PTT at the time of initial screen

- Patients who have had a hypersensitivity to either of the study medications

- Patients who are taking any other study medication(s). Patients will not be excluded
if they are on penicillin prophylaxis or folic acid, or use ibuprofen intermittently

- Patients taking tetracycline or sodium polystyrene sulfonate

- Patients on concomitant medications and other therapy must have a wash out period
prior to study entry and/or study drug dosing

- Patients with abnormal baseline ECG

- Patients with a history of hypotension or hypotensive episodes

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind

Outcome Measure:

To assess effects on red cell hydration.

Principal Investigator

Karen Kalinyak, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Hospital Medical Center, Cincinnati


United States: Food and Drug Administration

Study ID:

CCHMC 03-7-41



Start Date:

May 2005

Completion Date:

Related Keywords:

  • Anemia, Sickle Cell
  • dipyridamole
  • magnesium
  • sickle cell
  • anemia
  • red blood cells
  • Anemia
  • Anemia, Sickle Cell



Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Karmanos Cancer InstituteDetroit, Michigan  48201
University of CincinnatiCincinnati, Ohio  45267-0502