Please select the eligibility criteria that correspond to the clinical trial below.
Title: 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.


Options:
A: Inclusion Criteria:

* age 4-21 years, inclusive
* Sickle cell anemia (Hb SS) or Sickle beta zero thalassemia disease (Hb Sβ°)
* failed intravenous opioid pain management in the emergency department prior to the decision to admit the patient
* admitted to the inpatient unit for sickle cell pain crisis

Exclusion Criteria:

* patient received more than 12 hours of intravenous pain medication prior to enrollment
* previous enrollment in this study (only one admission per child is eligible)
* history of allergy/intolerance to both intravenous morphine and hydromorphone
* known other cause for pain (avascular necrosis, gall bladder disease, priapism, etc.)
* patient with greater than 10 admissions for pain crisis in the past year
* patient maintained on daily opioids or chronic transfusions for chronic sickle cell pain
* transfusion within the previous two months
* known kidney or liver failure (elevation of liver function tests does not warrant exclusion)
* known pulmonary hypertension
* pregnancy
* diagnosis of bacterial infection, fever ≥39.5°C, acute chest syndrome, hemodynamic instability or sepsis
* current oral magnesium supplementation or current enrollment in another therapeutic study protocol
* previously diagnosed clinical stroke
* current or planned use of neuromuscular blocker, nifedipine, ritodrine, or terbutaline
* allergy to magnesium sulfate
* discharge from an inpatient unit within 72 hours of arrival in the emergency department for the current pain crisis
B: Inclusion Criteria Stage I/II/IIb: (COMPLETE AND CLOSED TO ACCRUAL)

* Participants must have sickle cell anemia confirmed by hemoglobin analysis
* Participants must report that their pain is at baseline. Additionally, they cannot report an increase in dose or frequency of opioid use in the last 2 weeks prior to drug administration
* Age 21-70 years
* Participants must have the laboratory indices as outlined in the protocol
* Participants must have reliable IV access as determined by the investigator
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study.

Inclusion Criteria Stage III: (COMPLETE AND CLOSED TO ACCRUAL)

* Participants must have sickle cell anemia confirmed by hemoglobin analysis
* Participant is admitted to the hospital for a pain episode
* Age 21-70 years
* Participants must have the laboratory indices as outlined in the protocol
* Participants must have reliable IV access as determined by the investigator
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Inclusion Criteria Stage IV: (open, still accruing volunteers)

* Participants must have sickle cell disease confirmed by hemoglobin analysis
* Participant is admitted to the hospital for a pain episode
* Ages of assent (10 to 17 years at DFCI, but different depending on institution)
* Participants must have the laboratory indices as outlined in the protocol
* Participants must have reliable IV access as determined by the investigator
* Participants and parents must have the ability to understand and the willingness to sign a written informed consent and assent document
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria Stage I/II/IIb: (COMPLETE AND CLOSED TO ACCRUAL)

* Participants with a current physician diagnosis of asthma (within last 12 months), require continuous supplemental oxygen, or predicted or current use of some asthma medications.
* Participants with second- or third-degree AV block or sinus node dysfunction
* Have a history of bleeding diathesis
* Have a history of clinically overt stroke
* Have a history of severe hypertension not adequately controlled with anti-hypertensive medications
* Participants who are receiving chronic anti-coagulation or anti-platelet therapy
* Participants with a history of metastatic cancer
* Participants who have had a hospitalization or emergency room visit for any reason in the past 2 weeks
* Participants may not be receiving any other study agents or have received a study agent in the past 30 days
* Uncontrolled intercurrent illness
* Pregnant or breastfeeding women
* Participants with HIV
* Participants who have previously enrolled and received the investigational agent as part of this study
* Participants who are taking medications that may interact with the investigational agent

Exclusion Criteria Stage III: (COMPLETE AND CLOSED TO ACCRUAL)

* Participants with a current physician diagnosis of asthma (within last 12 months), require continuous supplemental oxygen, or predicted or current use of some asthma medications.
* Participants with second- or third-degree AV block or sinus node dysfunction
* Have a history of bleeding diathesis
* Have a history of clinically overt stroke
* Have a history of severe hypertension not adequately controlled with anti-hypertensive medications
* Participants who are receiving chronic anti-coagulation or anti-platelet therapy
* Participants with a history of metastatic cancer
* Participants may not be receiving any other study agents or have received a study agent in the past 30 days

Exclusion Criteria Stage IV: (open, still accruing volunteers)

* Participants with a current physician diagnosis of asthma (within last 12 months), require continuous supplemental oxygen, or predicted or current use of some asthma medications.
* Participants with second- or third-degree AV block or sinus node dysfunction
* Have a history of bleeding diathesis
* Have a history of clinically overt stroke
* Have a history of hypertension not adequately controlled with anti-hypertensive medications
* Participants who are receiving chronic anti-coagulation or anti-platelet therapy
* Participants with a history of metastatic cancer
* Participants may not be receiving any other study agents or have received a study agent in the past 30 days
* Participants with HIV
* Participants who have previously enrolled and received the investigational agent as part of this study
* Participants who are taking medications that may interact with the investigational agent
C: Postmenopausal women ages 50 to 79.
D: 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)

Answer: D