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Dipyridamole/Magnesium To Improve Sickle Cell Hydration

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ClinicalTrials.gov 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Recruitment Status : Withdrawn (The NHLBI BSMB recommended closure due to poor enrollment.)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
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Tracking Information
First Submitted Date  ICMJE January 11, 2006
First Posted Date  ICMJE January 13, 2006
Last Update Posted Date August 7, 2013
Study Start Date  ICMJE May 2005
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2006)
  • To assess effects on red cell hydration.
  • To assess effects on red cell survival. Measurements will be performed before and after treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: January 11, 2006)
  • 1) To assess effects on red cell hydration.
  • 2) To assess effects on red cell survival. Measurements will be performed before and after treatment.
Change History Complete list of historical versions of study NCT00276146 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2006)
  • To monitor side effects of each treatment arm.
  • To evaluate clinical outcomes during each phase of the study.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2006)
  • 1) To monitor side effects of each treatment arm.
  • 2) To evaluate clinical outcomes during each phase of the study.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dipyridamole/Magnesium To Improve Sickle Cell Hydration
Official Title  ICMJE Dipyridamole/Magnesium To Improve Sickle Cell Hydration
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).
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Condition  ICMJE Anemia, Sickle Cell
Intervention  ICMJE Drug: oral dipyridamole, oral magnesium, or a combination of both
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 5, 2013)
0
Original Enrollment  ICMJE
 (submitted: January 11, 2006)
66
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Not Provided
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00276146
Other Study ID Numbers  ICMJE CCHMC 03-7-41
U54HL070871 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Hospital Medical Center, Cincinnati
Study Sponsor  ICMJE Children's Hospital Medical Center, Cincinnati
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Karen Kalinyak, MD Children's Hospital Medical Center, Cincinnati
PRS Account Children's Hospital Medical Center, Cincinnati
Verification Date August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP