Dipyridamole/Magnesium To Improve Sickle Cell Hydration
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Anemia, Sickle Cell |
Drug: oral dipyridamole, oral magnesium, or a combination of both |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double-Blind |
| 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.
| Estimated Enrollment: | 66 |
| 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.
Eligibility| Ages Eligible for Study: | 12 Years and older |
| Genders Eligible for Study: | Both |
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
Contacts and Locations| 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 |
More Information
Additional Information:
No publications provided
| ClinicalTrials.gov Identifier: | NCT00276146 History of Changes |
| Other Study ID Numbers: | CCHMC 03-7-41, U54HL70871 |
| Study First Received: | January 11, 2006 |
| Last Updated: | August 8, 2008 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Children's Hospital Medical Center, Cincinnati:
|
dipyridamole magnesium sickle cell anemia red blood cells |
Additional relevant MeSH terms:
|
Anemia Anemia, Sickle Cell Hematologic Diseases Anemia, Hemolytic, Congenital Anemia, Hemolytic Hemoglobinopathies Genetic Diseases, Inborn Dipyridamole Phosphodiesterase Inhibitors |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Platelet Aggregation Inhibitors Hematologic Agents Therapeutic Uses Vasodilator Agents Cardiovascular Agents |
ClinicalTrials.gov processed this record on June 17, 2013