Dipyridamole/Magnesium To Improve Sickle Cell Hydration
Dipyridamole/Magnesium To Improve Sickle Cell Hydration
Sponsors
Source
Children's Hospital Medical Center, Cincinnati
Oversight Info
Has Dmc
Yes
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.
Overall Status
Withdrawn
Start Date
2005-05-01
Completion Date
N/A
Primary Completion Date
N/A
Phase
Phase 2
Study Type
Interventional
Primary 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
Measure |
|
To monitor side effects of each treatment arm. |
|
To evaluate clinical outcomes during each phase of the study. |
Condition
Intervention
Eligibility
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
Gender
All
Minimum Age
12 Years
Maximum Age
N/A
Overall Official
Last Name |
Role |
Affiliation |
|
Karen Kalinyak, MD |
Principal Investigator |
Children's Hospital Medical Center, Cincinnati |
Location
Facility |
|
Karmanos Cancer Institute Detroit Michigan 48201 United States |
|
University of Cincinnati Cincinnati Ohio 45219 United States |
|
Cincinnati Children's Hospital Medical Center Cincinnati Ohio 45229 United States |
Location Countries
Country
United States
Verification Date
2013-08-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
U54HL070871
Intervention Browse
Mesh Term
Dipyridamole
Firstreceived Results Date
N/A
Why Stopped
The NHLBI BSMB recommended closure due to poor enrollment.
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Crossover Assignment
Masking
Double
Study First Submitted
January 11, 2006
Study First Submitted Qc
January 11, 2006
Study First Posted
January 13, 2006
Last Update Submitted
August 5, 2013
Last Update Submitted Qc
August 5, 2013
Last Update Posted
August 7, 2013
ClinicalTrials.gov processed this data on October 15, 2018
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.