Decitabine for High-Risk Sickle Cell Disease
- In sickle cell disease (SCD), the proteins in the red blood cells that carry oxygen do not behave normally. In parts of the body where there are low levels of oxygen or where oxygen is used more, the sickle hemoglobin proteins may change shape and stick together. This causes the red cells to clump, which reduces blood flow. This leads to even lower oxygen levels and causes damage and/or pain.
- One way to stop the red blood cells from sticking together is to increase the levels of fetal (baby or good ) hemoglobin. The good hemoglobin then takes the place of the sickle hemoglobin.
- Hydroxyurea is the only approved drug for SCD. But hydroxyurea works in only about two-thirds of people with SCD. Even in those cases it sometimes stops working over time.
- Researchers are interested in testing decitabine. The drug may help to increase fetal hemoglobin levels. But it has not yet been approved to treat SCD.
- To test the safety and effectiveness of decitabine in increasing fetal hemoglobin levels and improving the symptoms of sickle cell disease.
- People at least 18 years of age who have sickle cell disease that has not improved after at least 6 months of hydroxyurea therapy. Those who cannot take hydroxyurea because of side effects may also participate.
- Participants will be screened with a physical exam and medical history. They will also have blood and urine tests, a lung function test, and other tests as required.
- Participants will receive decitabine injections up to twice a week for 1 year. Depending on the response to treatments, the dose will remain the same or be reduced to once a week.
- Participants will be monitored with frequent blood tests and other studies as directed by the study doctors.
- After the study is completed, participants will go back to their usual sickle cell care. If decitabine has improved a participant's SCD, treatment may be continued under regular health coverage insurance if this can be arranged.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Extended Phase 2 Study of Decitabine in Subjects With High Risk Sickle Cell Disease|
- The percentage change in HbF level from baseline to the average over the final 3 months of study. [ Time Frame: Final 3 months of study ] [ Designated as safety issue: No ]
- Clinical and laboratory assessment of safety, patient reported outcomes (PROMIS), frequency of crisis, measurements of hemolysis, coagulation, platelet activation, inflammation, endothelial damage, pulmonary arterial pressure, DNMT levels [ Time Frame: End of Study ] [ Designated as safety issue: No ]
- Clinical and laboratory assessment of global and beta-globin locus specific DNA methylation. [ Time Frame: End of Study ] [ Designated as safety issue: No ]
|Study Start Date:||June 2011|
|Study Completion Date:||February 2016|
|Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01375608
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Matthew M Hsieh, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|