Evaluating the Safety and Effectiveness of Hydroxyurea and Magnesium Pidolate to Treat People With Hemoglobin Sickle Cell Disease (CHAMPS) - Full Text View

Sponsored by:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00532883

Purpose

Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause intense pain episodes. Hemoglobin SCD (HbSC) is a form of SCD that is characterized by dense red blood cells. The purpose of this study is to evaluate the safety and effectiveness of hydroxyurea and magnesium pidolate, alone and combined, at reducing red blood cell density and the frequency of pain episodes in people with HbSC.

Condition	Intervention	Phase
Hemoglobin SC Disease	Drug: Hydroxyurea Drug: Magnesium Pidolate Other: Placebo Pills and Placebo Liquid	Phase II

Genetics Home Reference related topics: sickle cell disease

MedlinePlus related topics: Anemia Sickle Cell Anemia

Drug Information available for: Hydroxyurea Magnesium Magnesium pidolate Pyrrolidonecarboxylic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Effectiveness of Hydroxyurea and Magnesium Pidolate Alone and in Combination in Hemoglobin SC Disease: A Phase II Trial (CHAMPS)

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Density of hemoglobin sickle cell red cells (percent of red blood cells with density greater than 41 g/dL) [ Time Frame: Measured at Month 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Standard hematologic parameters, including hemoglobin level, mean cell volume (MCV), reticulocyte count, white blood cell count, platelet count, and absolute neutrophil count (ANC) [ Time Frame: Measured at Year 1 ] [ Designated as safety issue: No ]
Hemoglobin S, C, and F levels [ Time Frame: Measured at Year 1 ] [ Designated as safety issue: No ]
Red cell metabolic studies, including potassium chloride (K-Cl) co-transport activity, Gardos channel activity, sodium-magnesium (Na-Mg) exchanger activity, red cell cation content, and intracellular Mg [ Time Frame: Measured at Year 1 ] [ Designated as safety issue: No ]
Plasma total Mg and ionized Mg (iMg) levels [ Time Frame: Measured at Year 1 ] [ Designated as safety issue: No ]
Adhesion studies to laminin, thrombospondin, and endothelial cells; expression of red blood cell receptors and phosphatidylserine; and adhesive response to epinephrine [ Time Frame: Measured at Year 1 ] [ Designated as safety issue: No ]
Frequency of clinical vaso-occlusive events (e.g., pain events, acute chest syndrome) [ Time Frame: Measured at Year 1 ] [ Designated as safety issue: No ]

Estimated Enrollment:	188
Study Start Date:	January 2007
Estimated Study Completion Date:	May 2011
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Pills and Placebo Liquid: Placebo Comparator	Other: Placebo Pills and Placebo Liquid HU/Placebo capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)
Hydroxyurea Pills and Placebo Liquid: Active Comparator	Drug: Hydroxyurea HU capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)
Placebo Pills and Magnesium Pidolate Liquid: Active Comparator	Drug: Magnesium Pidolate HU/Placebo capsules (20 mg/kg/day for 11 months) Mg liquid (0.6 mEq/kg/day for 11 months)
Hydroxyurea Pills and Magnesium Pidolate Liquid: Active Comparator	Drug: Hydroxyurea HU capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months) Drug: Magnesium Pidolate HU/Placebo capsules (20 mg/kg/day for 11 months) Mg liquid (0.6 mEq/kg/day for 11 months)

Detailed Description:

SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain, which are called "sickle cell crises." SCD is caused by an abnormal type of hemoglobin, which is a protein inside red blood cells that carries oxygen. HbSC is a form of SCD that is characterized by the presence of dense red blood cells. People with HbSC usually develop less severe SCD symptoms than people with the more common form of the disease. There are limited treatment approaches aimed specifically at modifying the abnormal state of red blood cells. Also, few combination therapy treatments have been studied. The medication hydroxyurea is currently used to prevent sickle cell crises and to decrease the need for blood transfusions. The dietary supplement magnesium has not been widely studied as a treatment for SCD, but it may prevent dehydration, which may decrease the frequency of sickle cell crises. The purpose of this study is to evaluate the safety and effectiveness of hydroxyurea and magnesium pidolate, alone and combined, at reducing red blood cell density and the frequency of sickle cell crises in people with HbSC.

This 1-year study will enroll people with HbSC. Participants will be randomly assigned to one of the following four treatment groups:

Group 1 participants will receive placebo pills and placebo liquid.
Group 2 participants will receive hydroxyurea pills and placebo liquid.
Group 3 participants will receive placebo pills and magnesium pidolate liquid.
Group 4 participants will receive hydroxyurea pills and magnesium pidolate liquid.

Participants will receive the hydroxyurea or placebo pills once a day and the magnesium pidolate or placebo liquid twice a day for 11 months. Study visits will occur every 2 weeks during the first 2 months of the study, once a month for the following 9 months, and then at Year 1. At each visit, a physical exam and blood collection will occur. Selected visits will also include urine collection and a pregnancy test for female participants. Throughout the study, participants will record their study medication use in a daily diary.

Eligibility

Ages Eligible for Study:	5 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of HbSC disease
Hemoglobin level between 8 and 12.5 g/dL
At least one vaso-occlusive event (e.g., pain, acute chest syndrome) in the 12 months prior to study entry. An episode of pain is defined as the occurrence of pain in the extremities, back, abdomen, chest, or head that lasts at least 2 hours; requires a visit to a hospital, emergency room, clinic, or provider's office; and is not explained except by SCD. Acute chest syndrome is defined as a new pulmonary infiltrate on a chest x-ray associated with a fever (greater than 38.5° C), tachypnea, wheezing, cough, or chest pain.
Regular compliance with comprehensive care
In a steady disease state and not experiencing an acute complication of SCD (i.e., no hospitalization, pain event, or episode of acute chest syndrome within the 1 month prior to study entry)

Exclusion Criteria:

Previous transfusion with remaining hemoglobin A greater than 10%
Previous treatment with hydroxyurea within the last 3 months
Previous treatment with magnesium within the 3 months prior to study entry (including vitamins containing magnesium)
Poor compliance with previous treatment regimens
Liver dysfunction (SGPT greater than twice the upper limit of normal) within the 1 month prior to study entry
Kidney dysfunction (creatinine greater than or equal to 1.0 mg/dL for participants less than 18 years of age; greater than or equal to 1.2 mg/dL for participants 18 years of age or older) within the 1 month prior to study entry
Pregnant
Ten or more hospital admissions for pain in the 12 months prior to study entry
Daily use of narcotics
Treatment with any investigational drug in the 3 months prior to study entry
Less than 3% red blood cells with density greater than 41 g/dL (as measured by the ADVIA 120 system)
Positive HIV test
Other long-term illness or disorder other than SCD that could adversely affect performance in the study (e.g., tuberculosis)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00532883

Show 19 Study Locations

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Winfred C. Wang, MD

St. Jude Children's Research Hospital

More Information

Responsible Party:	St. Jude Children's Research Hospital ( Winfed C. Wang, MD )
Study ID Numbers:	515, U54 HL070587-06
Study First Received:	September 20, 2007
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00532883
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Sickle Cell Disease
Vaso-occlusive Event
Painful Crises
Acute Chest Syndrome

Study placed in the following topic categories:

Hemoglobin SC disease
Hematologic Diseases
Hydroxyurea
Hemoglobin SC Disease
Anemia
Anemia, Hemolytic
Pain

Sickle cell anemia
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hemoglobinopathies
Hemoglobinopathy
Anemia, Sickle Cell

Additional relevant MeSH terms:

Antisickling Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Hematologic Agents
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009