Dipyridamole/Magnesium To Improve Sickle Cell Hydration

This study has been withdrawn prior to enrollment.
(The NHLBI BSMB recommended closure due to poor enrollment.)
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT00276146
First received: January 11, 2006
Last updated: August 5, 2013
Last verified: August 2013
  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

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

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

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

Enrollment: 0
Study Start Date: May 2005
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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Criteria

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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00276146

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
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Karen Kalinyak, MD Children's Hospital Medical Center, Cincinnati
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Hospital Medical Center, Cincinnati
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 5, 2013
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 August 18, 2014