Hydroxyurea and Magnesium Pidolate to Treat People With Hemoglobin Sickle Cell Disease

NCT ID: NCT00532883

Last Updated: 2013-01-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2009-08-31

Brief Summary

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.

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.

Conditions

Hemoglobin SC Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo Pills and Placebo Liquid

Group Type: PLACEBO_COMPARATOR

Placebo Pills and Placebo Liquid

Intervention Type: OTHER

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

Group Type: ACTIVE_COMPARATOR

Hydroxyurea

Intervention Type: DRUG

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

Group Type: ACTIVE_COMPARATOR

Magnesium Pidolate

Intervention Type: DRUG

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

Group Type: ACTIVE_COMPARATOR

Hydroxyurea

Intervention Type: DRUG

HU capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)

Magnesium Pidolate

Intervention Type: DRUG

HU/Placebo capsules (20 mg/kg/day for 11 months) Mg liquid (0.6 mEq/kg/day for 11 months)

Interventions

Hydroxyurea

HU capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)

Intervention Type: DRUG

Magnesium Pidolate

HU/Placebo capsules (20 mg/kg/day for 11 months) Mg liquid (0.6 mEq/kg/day for 11 months)

Intervention Type: DRUG

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)

Intervention Type: OTHER

Eligibility 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)

• Minimum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Winfred C. Wang, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Children's Hospital and Research Center

Oakland, California, United States

University of California Davis

Sacramento, California, United States

University of Colorado

Aurora, Colorado, United States

University of Miami

Miami, Florida, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

University of Louisville

Louisville, Kentucky, United States

Johns Hopkins University

Baltimore, Maryland, United States

Boston Medical Center

Boston, Massachusetts, United States

Children's Hospital Boston

Boston, Massachusetts, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Montefiore Medical Center

The Bronx, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

Saint Christopher's Hospital

Philadelphia, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Children's Medical Center

Dallas, Texas, United States

Countries

United States

References

Wang W, Brugnara C, Snyder C, Wynn L, Rogers Z, Kalinyak K, Brown C, Qureshi A, Bigelow C, Neumayr L, Smith-Whitley K, Chui DH, Delahunty M, Woolson R, Steinberg M, Telen M, Kesler K. The effects of hydroxycarbamide and magnesium on haemoglobin SC disease: results of the multi-centre CHAMPS trial. Br J Haematol. 2011 Mar;152(6):771-6. doi: 10.1111/j.1365-2141.2010.08523.x. Epub 2011 Jan 31.

Reference Type: DERIVED

PMID: 21275961 (View on PubMed)

Other Identifiers

U54HL070587

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHAMPS-St. Jude

Identifier Type: -

Identifier Source: org_study_id