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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hemoglobin SC Disease

Intervention / Treatment
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* Drug: Hydroxyurea
* Drug: Magnesium Pidolate
* Other: Placebo Pills and Placebo Liquid


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Pills and Placebo Liquid<br> | Other: Placebo Pills and Placebo Liquid<br>* HU/Placebo capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)<br>|
| Active Comparator: Hydroxyurea Pills and Placebo Liquid<br> | Drug: Hydroxyurea<br>* HU capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)<br>|
| Active Comparator: Placebo Pills and Magnesium Pidolate Liquid<br> | Drug: Magnesium Pidolate<br>* HU/Placebo capsules (20 mg/kg/day for 11 months) Mg liquid (0.6 mEq/kg/day for 11 months)<br>|
| Active Comparator: Hydroxyurea Pills and Magnesium Pidolate Liquid<br> | Drug: Hydroxyurea<br>* HU capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)<br>Drug: Magnesium Pidolate<br>* HU/Placebo capsules (20 mg/kg/day for 11 months) Mg liquid (0.6 mEq/kg/day for 11 months)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Vaso-occlusive Event, Painful Crises, Acute Chest Syndrome