Magnesium Effects in Apheresis
|First Received Date ICMJE||June 22, 2002|
|Last Updated Date||March 3, 2008|
|Start Date ICMJE||June 2002|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00040235 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Magnesium Effects in Apheresis|
|Official Title ICMJE||Citrate Effects and Role of Prophylactic Magnesium Administration During Large-Volume Leukapheresis|
This study will determine whether magnesium replacement during apheresis can decrease side effects that donors commonly experience. Apheresis is a method of collecting large numbers of certain blood cells, such as white cells, stem cells, or platelets. In this procedure, whole blood is collected through a needle in an arm vein, similar to donating blood. The blood is separated into its components by centrifugation (spinning), the required cells are extracted, and the rest of the blood is returned to the body, either through the same needle or through another needle in the other arm.
When healthy people donate cells by apheresis, a blood thinner called citrate is added to prevent the blood from clotting in the apheresis machine. Citrate works by reducing calcium in the blood. When the blood is returned to the donor, citrate from the machine is also returned, lowering the donor's calcium levels. As a result, donors often feel tingling around the mouth, hands, and feet. Some of these symptoms can be prevented by giving calcium intravenously (through a vein) during the procedure. Even with the added calcium, however, some donors still have symptoms. Magnesium levels are also lowered by citrate, but it is not known if this causes symptoms. This study will examine whether the decrease in magnesium levels also contributes to the side effects of apheresis and whether magnesium replacement can reduce these symptoms.
Healthy apheresis donors 18 years of age or older who are enrolled in NIH protocols may participate in this study.
Donors will undergo the apheresis procedures required by the NIH protocol they are enrolled in. Throughout the procedure, they will receive an intravenous infusion of a salt solution that may or may not contain magnesium. Blood samples of 5 milliliters (1 teaspoon) each will be taken from the apheresis machine at the beginning and end of the procedure and at 30- to 60-minute intervals during the procedure. No more than 50 ml (3 tablespoons) will be taken during any single apheresis. The last sample will be drawn 60 minutes after completion of the apheresis. In addition, donors will:
Large volume leukapheresis (LVL) is increasingly used to collect peripheral blood stem cells (PBSCs) and other mononuclear cells (MNC) for hematopoietic and immune reconstitution, with recent emphasis on increased processing volumes. Decreases in divalent cation levels caused by administration of citrate anticoagulant during LVL can be associated with severe donor reactions, and may limit the rate at which blood can be processed. Several donors at NIH experienced citrate-related hypocalcemic tetany during LVL, in response to which we developed standard operating procedures for the routine administration of prophylactic intravenous calcium solutions during longer apheresis procedures. Other centers have utilized heparin to reduce the amount of citrate returned to the donor, however, this exposes the donor to systemic anticoagulation and may be associated with hematomas or clumping of the apheresis product.
We previously determined that citrate administration during apheresis results in significant excretion of calcium and magnesium in the urine during the procedure, and that performance of prolonged or repeated LVL causes significant depletion of blood calcium and magnesium levels. Decreases in calcium levels were ameliorated during procedures performed with prophylactic calcium administration. Our preliminary studies also demonstrated that ionized magnesium levels were markedly reduced during LVL as well as plateletpheresis procedures. The clinical impact of severe, acute decreases in ionized magnesium levels in healthy apheresis donors is not clear, however. Since most of the adverse effects related to citrate administration can be prevented by prophylactic calcium administration, it is unknown what aspect of the remaining discomfort may be attributable to hypomagnesemia. This protocol will focus on determining the contribution of acute hypomagnesemia to citrate-related symptoms during large-volume apheresis, and establishing the role of and indications for prophylactic intravenous magnesium replacement in this setting. The study plan will consist of a prospective, randomized, placebo-controlled, double-blind study. Healthy allogeneic donors will be assigned to one of two treatment groups. One group will receive intravenous magnesium infusions throughout scheduled LVL procedures; the other group will receive equivalent volume infusions of normal saline. Symptoms and blood samples will be obtained by apheresis nurses and laboratory assays will be performed by associate laboratory investigators, all in a blinded fashion.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Endpoint Classification: Efficacy Study
Primary Purpose: Treatment
|Intervention ICMJE||Procedure: magnesium|
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||February 2004|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Healthy allogeneic subjects enrolled on NIH LVL protocols, with approval of the PI:
NHLBI protocols-99-H-0046, 99-H-0050, 99-H-0064, 98-H-0122, 98-H-0006, 97-H-0202, 97-H-0196, 98-H-0154, 01-H-0162, 01-H-0010, 02-H-0111;
NIAID protocols -98-I-0104, 01-I-0013;
NCI protocols-00-C-0119, 00-C-0201, 00-C-0206
Weight greater than or equal to 40 kg
Bilateral peripheral venous access
Minimum LVL volume of 12 liters processed (per subject's primary protocol)
Hematocrit greater than or equal to 35 percent
Normal serum electrolyte, calcium and magnesium values
Normal hepatic and kidney function tests
Able to give informed consent
Age greater than 18 years.
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00040235|
|Other Study ID Numbers ICMJE||020234, 02-CC-0234|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institutes of Health Clinical Center (CC)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||February 2004|
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