Dipyridamole/Magnesium To Improve Sickle Cell Hydration

August 5, 2013 updated by: Children's Hospital Medical Center, Cincinnati
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).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
To monitor side effects of each treatment arm.
To evaluate clinical outcomes during each phase of the study.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Investigators

  • Principal Investigator: Karen Kalinyak, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Study Registration Dates

First Submitted

January 11, 2006

First Submitted That Met QC Criteria

January 11, 2006

First Posted (Estimate)

January 13, 2006

Study Record Updates

Last Update Posted (Estimate)

August 7, 2013

Last Update Submitted That Met QC Criteria

August 5, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCHMC 03-7-41
  • U54HL070871 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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