Dipyridamole/Magnesium To Improve Sickle Cell Hydration

Anemia, Sickle Cell Clinical Trial

Official title:

Dipyridamole/Magnesium To Improve Sickle Cell Hydration

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00276146
• Other study ID #: CCHMC 03-7-41
• Secondary ID: U54HL070871
• Status: Withdrawn
• Phase: Phase 2
• First received: January 11, 2006
• Last updated: August 5, 2013
• Start date: May 2005

Study information

• Verified date: August 2013
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Gender: Both
• Age group: 12 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell

Intervention

Drug:
• oral dipyridamole, oral magnesium, or a combination of both

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess effects on red cell hydration.
Primary	To assess effects on red cell survival. Measurements will be performed before and after treatment.
Secondary	To monitor side effects of each treatment arm.
Secondary	To evaluate clinical outcomes during each phase of the study.

External Links

•   Sickle Cell Center at Cincinnati Children's Hospital Medical Center