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Dipyridamole/Magnesium To Improve Sickle Cell Hydration

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00276146
Recruitment Status : Withdrawn (The NHLBI BSMB recommended closure due to poor enrollment.)
First Posted : January 13, 2006
Last Update Posted : August 7, 2013
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Anemia, Sickle Cell Drug: oral dipyridamole, oral magnesium, or a combination of both Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Official Title: Dipyridamole/Magnesium To Improve Sickle Cell Hydration
Study Start Date : May 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia

Primary Outcome Measures :
  1. To assess effects on red cell hydration.
  2. To assess effects on red cell survival. Measurements will be performed before and after treatment.

Secondary Outcome Measures :
  1. To monitor side effects of each treatment arm.
  2. To evaluate clinical outcomes during each phase of the study.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All

Inclusion Criteria:

  • Patients with homozygous sickle cell (Hb SS) confirmed by hemoglobin electrophoresis or HPLC
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00276146

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United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45219
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
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Principal Investigator: Karen Kalinyak, MD Children's Hospital Medical Center, Cincinnati

Additional Information:
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Responsible Party: Children's Hospital Medical Center, Cincinnati Identifier: NCT00276146    
Other Study ID Numbers: CCHMC 03-7-41
U54HL070871 ( U.S. NIH Grant/Contract )
First Posted: January 13, 2006    Key Record Dates
Last Update Posted: August 7, 2013
Last Verified: August 2013
Keywords provided by Children's Hospital Medical Center, Cincinnati:
sickle cell
red blood cells
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Genetic Diseases, Inborn
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Vasodilator Agents