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

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ClinicalTrials.gov Identifier: NCT00532883
Recruitment Status : Terminated (Enrollment has been terminated due to a slow rate of enrollment.)
First Posted : September 21, 2007
Results First Posted : May 11, 2010
Last Update Posted : January 18, 2013
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Tracking Information
First Submitted Date  ICMJE September 20, 2007
First Posted Date  ICMJE September 21, 2007
Results First Submitted Date  ICMJE April 1, 2010
Results First Posted Date  ICMJE May 11, 2010
Last Update Posted Date January 18, 2013
Study Start Date  ICMJE January 2007
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 21, 2010)
Distribution of the Density of Hemoglobin SC Red Cells [ Time Frame: measured 2 months after initiation of treatment ]
An individuals' percentage of red blood cells with density greater than 41 g/dL as measured by Advia.
Original Primary Outcome Measures  ICMJE
 (submitted: September 20, 2007)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2007)
  • 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 ]
  • Hemoglobin S, C, and F levels [ Time Frame: Measured at Year 1 ]
  • 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 ]
  • Plasma total Mg and ionized Mg (iMg) levels [ Time Frame: Measured at Year 1 ]
  • 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 ]
  • Frequency of clinical vaso-occlusive events (e.g., pain events, acute chest syndrome) [ Time Frame: Measured at Year 1 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hydroxyurea and Magnesium Pidolate to Treat People With Hemoglobin Sickle Cell Disease
Official Title  ICMJE Effectiveness of Hydroxyurea and Magnesium Pidolate Alone and in Combination in Hemoglobin SC Disease: A Phase II Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hemoglobin SC Disease
Intervention  ICMJE
  • 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)
  • 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)
Study Arms  ICMJE
  • Placebo Comparator: Placebo Pills and Placebo Liquid
    Intervention: Other: Placebo Pills and Placebo Liquid
  • Active Comparator: Hydroxyurea Pills and Placebo Liquid
    Intervention: Drug: Hydroxyurea
  • Active Comparator: Placebo Pills and Magnesium Pidolate Liquid
    Intervention: Drug: Magnesium Pidolate
  • Active Comparator: Hydroxyurea Pills and Magnesium Pidolate Liquid
    Interventions:
    • Drug: Hydroxyurea
    • Drug: Magnesium Pidolate
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 21, 2010)
44
Original Estimated Enrollment  ICMJE
 (submitted: September 20, 2007)
188
Actual Study Completion Date  ICMJE August 2009
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00532883
Other Study ID Numbers  ICMJE CHAMPS-St. Jude
U54HL070587 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party St. Jude Children's Research Hospital
Study Sponsor  ICMJE St. Jude Children's Research Hospital
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Winfred C. Wang, MD St. Jude Children's Research Hospital
PRS Account St. Jude Children's Research Hospital
Verification Date January 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP