Hemoglobin SC Disease
Conditions
Keywords
Sickle Cell Disease, Vaso-occlusive Event, Painful Crises, Acute Chest Syndrome
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.
Interventions
DRUGHydroxyurea
HU capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)
HU/Placebo capsules (20 mg/kg/day for 11 months) Mg liquid (0.6 mEq/kg/day for 11 months)
OTHERPlacebo 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)
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
St. Jude Children's Research Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of the Density of Hemoglobin SC Red Cells | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from October 2006 through June 2008 at 10 sites across the United States. Subjects were recruited from sickle cell specific clinics.
Pre-assignment details
Subjects were screened to ensure specific laboratory measurement levels after enrollment but prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Hydroxyurea/Magnesium Hydroxyurea (20 mg/kg/day) combined with liquid magnesium pidolate (0.6 mEq/kg/day). | 11 |
| Hydroxyurea/Mg Placebo Hydroxyurea (20 mg/kg/day) combined with liquid Mg placebo. | 12 |
| HU Placebo/Magnesium HU placebo combined with liquid magnesium pidolate (0.6 mEq/kg/day). | 10 |
| HU Placebo/Mg Placebo Placebo for both hydroxyurea (20 mg/kg/day) and liquid magnesium pidolate (0.6 mEq/kg/day). | 11 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 1 |
| Overall Study | Early Study Termination | 4 | 4 | 1 | 4 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 | 0 |
| Overall Study | Subject was Nonadherent | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Hydroxyurea/Mg Placebo | HU Placebo/Magnesium | Hydroxyurea/Magnesium | HU Placebo/Mg Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 9 Participants | 10 Participants | 9 Participants | 37 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 7 Participants |
| Age Continuous | 16.8 years STANDARD_DEVIATION 12.6 | 14.8 years STANDARD_DEVIATION 8.45 | 12.5 years STANDARD_DEVIATION 4.41 | 17.3 years STANDARD_DEVIATION 12.41 | 16.7 years STANDARD_DEVIATION 9.81 |
| Region of Enrollment United States | 12 participants | 10 participants | 11 participants | 11 participants | 44 participants |
| Sex: Female, Male Female | 8 Participants | 3 Participants | 4 Participants | 4 Participants | 19 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 7 Participants | 7 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 11 | 10 / 12 | 9 / 10 | 10 / 11 |
| serious Total, serious adverse events | 3 / 11 | 2 / 12 | 3 / 10 | 2 / 11 |
Outcome results
Primary
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.
Time frame: measured 2 months after initiation of treatment
Population: ITT: All randomized subjects who receive any clinical trial material. Subjects in the ITT population will be classified according to the treatment group to which they were randomized, regardless of what study drug they received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxyurea/Magnesium | Distribution of the Density of Hemoglobin SC Red Cells | 12.09 percent of cells | Standard Deviation 5.075 |
| Hydroxyurea/Mg Placebo | Distribution of the Density of Hemoglobin SC Red Cells | 11.16 percent of cells | Standard Deviation 7.296 |
| HU Placebo/Magnesium | Distribution of the Density of Hemoglobin SC Red Cells | 10.49 percent of cells | Standard Deviation 4.572 |
| HU Placebo/Mg Placebo | Distribution of the Density of Hemoglobin SC Red Cells | 12.79 percent of cells | Standard Deviation 3.739 |
Comparison: F-test from a longitudinal mixed model (controlling for baseline measurement)testing the hypothesis of no difference in mean percent dense cells between the four treatment groups at Visit 6. The study was originally powered to detect a difference of 20%, but it was stopped early.p-value: 0.93Mixed Models Analysis