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

Effectiveness of Hydroxyurea and Magnesium Pidolate Alone and in Combination in Hemoglobin SC Disease: A Phase II Trial

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.

Study Overview

• Status: Terminated
• Conditions: Hemoglobin SC Disease
• Intervention / Treatment: Other: Placebo Pills and Placebo Liquid; Drug: Hydroxyurea; Drug: Magnesium Pidolate

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: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Oakland, California, United States, 94609-1809
      • Children's Hospital and Research Center
    • Sacramento, California, United States, 95817
      • University of California Davis
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30342-1600
      • Children's Healthcare of Atlanta
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02118
      • Children's Hospital Boston
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New York
    • Bronx, New York, United States, 10463
      • Montefiore Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati CHildren's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19444
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19134-1095
      • Saint Christopher's Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo Pills and Placebo Liquid	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)
ACTIVE_COMPARATOR: Hydroxyurea Pills and Placebo Liquid	Drug: Hydroxyurea; HU capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)
ACTIVE_COMPARATOR: Placebo Pills and Magnesium Pidolate Liquid	Drug: Magnesium Pidolate; HU/Placebo capsules (20 mg/kg/day for 11 months) Mg liquid (0.6 mEq/kg/day for 11 months)
ACTIVE_COMPARATOR: Hydroxyurea Pills and Magnesium Pidolate Liquid	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of the Density of Hemoglobin SC Red Cells	An individuals' percentage of red blood cells with density greater than 41 g/dL as measured by Advia.	measured 2 months after initiation of treatment

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Winfred C. Wang, MD, St. Jude Children's Research Hospital

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (ACTUAL): March 1, 2009
• Study Completion (ACTUAL): August 1, 2009

Study Registration Dates

• First Submitted: September 20, 2007
• First Submitted That Met QC Criteria: September 20, 2007
• First Posted (ESTIMATE): September 21, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): January 18, 2013
• Last Update Submitted That Met QC Criteria: January 14, 2013
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: Sickle Cell Disease; Acute Chest Syndrome; Painful Crises; Vaso-occlusive Event
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Hemoglobin SC Disease; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: CHAMPS-St. Jude; U54HL070587 (U.S. NIH Grant/Contract)