Transfer of GPI-Linked Proteins to Transfused Patients With Paroxysmal Nocturnal Hemoglobinuria
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|ClinicalTrials.gov Identifier: NCT00039923|
Recruitment Status : Completed
First Posted : June 17, 2002
Last Update Posted : March 4, 2008
|First Submitted Date||June 14, 2002|
|First Posted Date||June 17, 2002|
|Last Update Posted Date||March 4, 2008|
|Study Start Date||June 2002|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures||Not Provided|
|Original Primary Outcome Measures||Not Provided|
|Change History||Complete list of historical versions of study NCT00039923 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures||Not Provided|
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||Transfer of GPI-Linked Proteins to Transfused Patients With Paroxysmal Nocturnal Hemoglobinuria|
|Official Title||A Pilot Study to Determine if Transfer of Gpi-Linked Proteins Occurs Following Transfusion of Red Cells to Patients With Paroxysmal Nocturnal Hemoglobinuria|
This study will examine blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) after they receive a blood transfusion to determine if certain proteins (GPI-linked proteins) in the transfused blood transfer to the patient's blood cells. GPI-linked proteins, which are normally present on red cells and regulate red cell survival, are absent in patients with PNH. Their lack is believed to account for the premature destruction of red blood cells in these patients, resulting in a low hemoglobin and hematocrit. Patients may experience fatigue, flank pain and other symptoms, requiring treatment with blood transfusion.
Patients with PNH 18 years of age or older with group A1 blood who require at least three units of red cells and who have not been transfused with group O blood within the last 3 months may be eligible for this study.
Participants will come to the NIH Clinical Center for the following procedures:
Blood samples of 3 teaspoons each will be drawn 1 day, 1 week, and 3 weeks after the transfusion. These samples may be collected by the patient's doctor locally and sent to NIH by mail.
If it is found that GPI-linked proteins transfer to the patient's cells, the study will also examine how long the proteins remain attached and will assess whether the proteins are functional and prevent cell destruction.
|Detailed Description||Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal bone marrow disorder, resulting from an acquired, somatic X-linked mutation of the PIG-A gene in an hematopoietic stem cell. Absence of PIG-A function in a cell prevents synthesis of the glycosylphosphatidylinositol (GPI) moiety, which anchors many different types of proteins to the cell membrane. Intravascular red cell destruction, the hallmark of the disorder, is caused by susceptibility of the abnormal erythrocyte to complement-mediated lysis; this sensitivity is due to lack of CD59, a potent inhibitor of the late components of complement and reactive lysis. In vitro studies from this laboratory have demonstrated transfer of GPI-linked proteins, CD55 and CD59, from normal to deficient cells and transfer is associated with resistance to hemolysis. Patients with PNH frequently require transfusion as their standard care. In addition, patients with all blood groups requiring transfusion will often receive compatible group O blood. Group O blood is prevalent in blood bank inventories; and red cell survival after transfusion is equal to that after transfusion of "in group" blood. The purpose of this study is to examine protein transfer of GPI-linked proteins from transfused cells to deficient cells obtained from patients with PNH. Patients with group A(1) blood will receive compatible group O blood so that donor and recipient blood cells can be discriminated. Flow cytometric studies will be performed subsequently to determine if transfer of GPI-linked protein to patients' cells has occurred.|
|Study Design||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Original Enrollment||Same as current|
|Study Completion Date||June 2005|
|Primary Completion Date||Not Provided|
The following must be met before the subject may be enrolled:
PNH patients with group A(1) blood who require at least three units of red cells as judged by their primary care physician; criteria for transfusion would include hemoglobin below 7.5 g/dl or symptoms related to anemia (impaired exercise tolerance, angina, shortness of breath) that warrant therapy.
A PNH clone of greater than 40% and not have been transfused with group O blood for at least three months previously.
Eighteen years of age or older.
Karnofsky performance status of 60% or better.
Adequate organ function as defined by serum creatinine less than 2.0 mg/dl.
Able to comprehend and willing to sign an informed consent.
Any one of the following eliminates a subject from participating:
Evidence of uncontrolled infection.
Known alloimmunization to red cell antigens.
Treatment with investigational agent or hematopoietic growth factors within 4 weeks of study entry.
Psychiatric, addictive or any disorder that compromises ability to give truly informed consent.
Patients who are moribund or who have concurrent hepatic, renal, cardiac disease.
|Ages||Child, Adult, Older Adult|
|Accepts Healthy Volunteers||No|
|Contacts||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries||United States|
|Removed Location Countries|
|Other Study ID Numbers||020227
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor||National Heart, Lung, and Blood Institute (NHLBI)|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||June 2005|