View clinical trials related to Sickle Cell Disease.
Filter by:The purpose of this study is to determine whether simvastatin is effective in reducing the frequency and intensity of vaso-occlusive pain episodes in patients with sickle cell disease.
The investigators propose to determine the engraftment and transplant related morbidity and mortality after a non-myeloablative allogeneic hematopoietic stem cell transplant protocol using immune- suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy in patients with aggressive sickle cell disease who are not candidates for or experienced complications from hydroxyurea therapy. Fully HLA matched siblings will be used as donors for hematopoietic stem cells to reduce the risk of morbidity and mortality in this cohort of patients.
The goal of this clinical research study is to find out about the safety and effects of a drug called panobinostat when given to adults with sickle cell disease. Panobinostat is a pan histone deacetylase (HDAC) inhibitor. HDAC inhibitors have been shown to significantly increase hemoglobin F induction, which is well documented to improve outcomes in sickle cell disease. HDAC inhibitors are also known to potently inhibit cell-specific inflammation, which is a primary contributor to the debilitating effects of sickle cell disease. Given the relevance of these mechanisms of action in SCD, panobinostat may prove to contribute significantly to the management of SCD patients, a population in critical need of further effective treatment options.
This study will collect representative blood samples from healthy children and adults and from children and adults who have unique red blood cell features that are related to sickle cell disease. Sickle cell disease is a blood disease that limits the ability of red blood cells to carry oxygen throughout the body. The purpose of the study is to collect a variety of blood samples that may then be used to investigate advances and potential new drug treatments for sickle cell disease. Volunteers must be at least 18 years of old. Samples will be taken both from healthy volunteers and from volunteers who have unique red blood cell features that are related to sickle cell disease. Candidates will be screened with a medical history. During the study, participants will undergo a one- to two-hour outpatient procedure at the National Institutes of Health Clinical Center. Once researchers have explained the study and obtained the participant s consent, participants will donate 8 cc (approximately 2 teaspoons) of blood. Because repeat testing helps researchers validate study findings, participants who have the unique red blood cell features mentioned above may also be asked if they are willing to return and donate another 2 cc to 8 cc of blood for additional studies. The amount of blood drawn will not exceed 50 ml with any eight-week period for adults or 7 cc within any six-week period for children....
Hypothesis 1: A novel nonmyeloablative condition regimen will be safe and efficacious in producing stable donor chimerism and cure of severe hemoglobinopathy. Hypothesis 2: Stable donor chimerism will result in amelioration of cerebral vasculopathy, improved cerebral perfusion and neurocognitive function. Specific Aim 1: Study the safety and efficacy of a novel non-toxic conditioning regimen for HSCT for patients with severe hemoglobinopathies and the kinetics of lineage specific chimerism after HSCT We will test our hypothesis that a novel nonmyeloablative condition regimen will be safe and efficacious in producing stable donor chimerism and cure of severe hemoglobinopathy: Specific Aim 2: Optimize the immunosuppressive regimen for HSCT patients through a thorough understanding of the pharmacokinetics of Busulfan (BU) and mycophenolate mofetil (MMF) in the patient population. This will involve: 1. Determine the pharmacokinetics of intravenously and orally administered MMF and intravenous BU in patients receiving HSCT. 2. Determine the relationship of Area under the curve (AUC) of BU and mean trough concentrations of mycophenolic acid (MPA) to engraftment and graft versus host disease (GVHD). 3. Determine the relationship of Area under the curve (AUC) and steady state concentration of BU to engraftment at day 30 and 1 year post HSCT. Specific Aim 3: Study the effect of complete or partial donor chimerism on silent and overt cerebral vasculopathy, and neurocognitive functioning in patients with SCD undergoing HSCT. We will test our hypothesis that stable donor chimerism will result in improvement in cerebral vasculopathy and neurocognitive function. This will include. 1. Determine effect of transplantation silent and overt cerebral vasculopathy by comparison MRA and TCD 1 year after HSCT to pre-HSCT studies. 2. Determine effect on HSCT on neurocognitive function. Specific Aim 4: To determine the rate of T cell immune reconstitution in children with sickle cell disease following myeloablative compared to nonmyeloablative stem cell transplantation, using immunophenotyping assays, CDR3 spectratyping TREC analysis, and measurement of T cell specific donor engraftment.
The collection of human specimens from both patients and healthy volunteers is necessary for the development of laboratory assays to further basic and clinical research studies. This protocol defines the purposes for which specimens will be collected and establishes general conditions under which sample collection will be performed.
This study will determine the best ways to collect, process and store umbilical cord blood from babies with sickle cell disease, sickle cell trait and unaffected babies. Sickle cell disease is an abnormality of the hemoglobin in red blood cells that causes the cells to change shape and clump together, preventing their normal flow in the bloodstream. This impairs blood flow to various organs, and the resulting oxygen deprivation causes organ damage. Cord blood is rich in stem cells (cells produced in the bone marrow that mature to different types of blood cells), which may prove useful in new sickle cell therapies. However, cord blood from babies with sickle cell trait, sickle cell disease and normal babies may act differently under laboratory conditions, so it is important to learn how best to work with blood from all three groups of babies for future use in possible treatments. Pregnant women between 18 and 45 years of age who are at risk of having an infant with sickle cell disease and normal volunteers who are pregnant and not at risk for this disease may be eligible for this study. Potential participants will be counseled about donating her infant s blood in order to make an informed choice. All women who participate in the study will provide a medical history and have blood collected from the umbilical cord and placenta (afterbirth) after the baby s delivery. The blood will be tested for various infectious diseases, processed, frozen and stored for research purposes. In addition, blood from women with babies at risk for sickle cell disease will be tested for the presence of the sickle cell gene, tissue typed, and used for research as follows: - Sickle cell disease - If cord blood tests show the baby has sickle cell disease, the blood will be frozen for an indefinite period of time for possible use in future treatment of the child. This treatment could include stem cell transplantation or gene therapy, treatments are not currently considered routine for sickle cell disease. - Sickle cell trait or normal hemoglobin - If cord blood tests show the baby has sickle cell trait or is unaffected, the blood will be processed and stored for up to 3 years, during which time it may possibly be used to treat a currently living or future sibling with sickle cell disease. After 3 years, the participant may agree to either have the blood discarded, given to research or moved to another facility for continued storage at the participant s expense, if there is a storage fee. Alternatively, if there is no anticipated future need for the collected blood, or if it does not meet standards needed for future treatment, it will be used in NIH-approved research studies. Participants and their family doctor or the baby s pediatrician will be contacted twice a year for information about changes in the baby s health. Participants may also be asked permission to perform new tests developed by researchers. ...