117 Clinical Trials for Various Conditions
The study aims to test if a new medicine called etavopivat potentially affects other medicines in healthy participants. The purpose of the study is to investigate whether the use of etavopivat affects the breakdown and metabolism of commonly used medicines in the body. During the study, participants will receive etavopivat and five different medicines that are already approved and available on the market, and which can be prescribed by doctors. These marketed medicines are called substrate drugs and they are: digoxin, pitavastatin, metformin, midazolam, and rosuvastatin. During a period of the study, participants will take 2 tablets of etavopivat daily for 10 consecutive days. The study will last for about 34 to 64 days.
Etavopivat is a new medicine under development for treating blood disorders like sickle cell disease and thalassaemia. Sickle cell disease and thalassaemia are inherited blood disorders that affect haemoglobin. Haemoglobin is the protein that carries oxygen through the body. This study is looking into how safe treatment with etavopivat is and how well it works over a long period of time. The study will last for up to 264 weeks, but it will end earlier if etavopivat is approved in the participant's country.
The purpose of this study is to evaluate the effect of food on the amount of etavopivat in the bloodstream of healthy participants. Participants will take a single oral dose of etavopivat following a high-fat meal (i.e. fed) and on an empty stomach (i.e fasted) on two separate occasions.The study will last up to 50 days (including screening).
Allogeneic Stem Cell Transplantation of NiCord®, Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells, in Patients with Hemoglobinopathies
The design of the study incorporates the following features: 1. This is a phase II study to determine the safety and therapeutic potential of a new transplant approach (disease-free survival, graft versus myeloma effect) and to evaluate its toxicity profile (immediate toxicity, graft-versus-host disease, graft rejection, mortality) in a patient population with severe congenital anemias. 2. The patient cohort to be studied: Those patients with severe sickle cell disease and thalassemia who have risk factors for high mortality and morbidity related to their disease 3. Transplant Conditioning Regimen - Immunosuppression without myeloablation: Patients will receive conditioning sufficient to allow donor lympho-hematopoietic engraftment without complete marrow ablation. If the graft is rejected, the patient will reconstitute autologous marrow function. We will use a combination of low dose irradiation, Alemtuzumab (Campath®), and sirolimus. 4. Peripheral blood hematopoietic progenitor cell (PBPC) transplant: An unmanipulated peripheral blood stem cell collection from a filgrastim (G-CSF) stimulated HLA-matched donor should improve the chance of engraftment because of the high stem cell dose (5 x 106/kg CD34+ cells) and the presence of donor lymphocytes. To reduce the risk of GVHD, patients will receive sirolimus before and after the transplant. The sirolimus will be tapered as necessary to minimize any graft versus host disease while still maintaining adequate chimerism.
The primary purpose of this study is to see if giving lower doses of chemotherapy (moderately ablative) will result in successful bone marrow replacement without as severe side-effects but with permanent control of the disease. Patients will receive a chemotherapy regimen with busulfan, fludarabine, and alemtuzumab followed by an infusion of stem cells, either from a family-related or cord-blood matched donor.
The purpose of this study is to find out if using a lower dose of chemotherapy before stem cell transplantation can cure patients of sickle cell anemia or thalassemia while causing fewer severe side effects than conventional high dose chemotherapy with transplantation.
This study will develop a national cord blood bank for siblings of patients with hemoglobinopathies and thalassemia.
Hematopoietic Cell Transplantation/HCT involves receiving healthy blood-forming cells (stem cells) from a donor to replace the diseased or damaged cells in participants' bone marrow. The researchers think giving participants treatment with fludarabine and dexamethasone, drugs that lower the activity of the body's immune system (immune suppression), before standard conditioning therapy and HCT may help prevent serious side effects, including graft failure and GvHD. In this study, depending on how participants' body responds to the fludarabine and dexamethasone, the study doctor may decide participants should receive another drug, called cyclophosphamide, instead of fludarabine. In addition, depending on the results of participants' routine blood tests, participants may receive the drugs bortezomib and rituximab, which also help with immune suppression.
Background: Sickle cell disease (SCD) is an inherited disorder of the blood. It can damage a person s organs and cause serious illness and death. A blood stem cell transplant is the only potential cure for SCD. Treatments that improve survival rates are needed. Objective: To find out if a new antibody drug (briquilimab, JSP191) improves the success of a blood stem cell transplant Eligibility: People aged 13 or older who are eligible for a blood stem cell transplant to treat SCD. Healthy family members over age 13 who are matched to transplant recipients are also needed to donate blood. Design: Participants receiving transplants will undergo screening. They will have blood drawn. They will have tests of their breathing and heart function. They may have chest x-rays. A sample of marrow will be collected from a pelvic bone. Participants will remain in the hospital about 30 days for the transplant and recovery. They will have a large intravenous line inserted into the upper arm or chest. The line will remain in place for the entire transplant and recovery period. The line will be used to draw blood as needed. It will also be used to administer the transplant stem cells as well as various drugs and blood transfusions. Participants will also receive some drugs by mouth. Participants must remain within 1 hour of the NIH for 3 months after transplant. During that time, they will visit the clinic up to 2 times a week. Follow-up visits will include tests to evaluate participants mental functions. They will have MRI scans of their brain and heart.
Primary Objectives: Long-term safety of BIVV003 in participants with severe sickle cell disease (SCD) and ST- 400 in participants with transfusion-dependent beta-thalassemia (TDT) Secondary Objectives: * Long-term efficacy of the biological treatment effect of BIVV003 in SCD * Long-term efficacy of the clinical treatment effect of BIVV003 on SCD-related clinical events * Long-term efficacy of the biological treatment effect of ST-400 in TDT * Long-term efficacy of the clinical treatment effect of ST-400 in TDT
Background: - Some sickle cell disease or beta-thalassemia can be cured with transplant. Researchers want to test a variation of transplant that uses low dose radiation and a combination of immunosuppressive drugs. They want to know if it helps a body to better accept donor stem cells. Objectives: - To see if low dose radiation (300 rads), oral cyclophosphamide, pentostatin, and sirolimus help a body to better accept donor stem cells. Eligibility: - People 4 and older with beta-thalassemia or sickle cell disease that can be cured with transplant, and their donors. Design: * Participants and donors will be screened with medical history, physical exam, blood test, tissue and blood typing, and bone marrow sampling. They will visit a social worker. * Donors: * may receive an intravenous (IV) tube in their groin vein. * will receive a drug injection daily for 5 or 6 days to move the blood stem cells from the bone marrow into general blood circulation. * will undergo apheresis: an IV is put into a vein in each arm. Blood is taken from one arm, a machine removes the white blood cells that contain blood stem cells, and the rest is returned through the other arm. * Participants: * may undergo red cell exchange procedure. * will remain in the hospital for about 30 days. * will receive a large IV line that can stay in their body from transplant through recovery. * will receive a dose of radiation, and transplant related drugs by mouth or IV. * will receive blood stem cells over 8 hours by IV. * will take neuropsychological tests and may complete questionnaires throughout the transplant process. * must stay near NIH for 4 months. They will visit the outpatient clinic weekly.
The study is designed as a Pilot/Phase 1 trial of reduced intensity Haploidentical HSCT in patients with sickle cell disease and thalassemia. The purpose of the study is to assess the safety and toxicity of reduced intensity conditioning haploidentical hematopoietic stem cell transplantation.
The purpose of this research is to evaluate the effects of L-glutamine as a therapy for Sickle Cell Anemia or Sickle ß0 Thalassemia as evaluated by the number of occurrences of sickle cell crises.
The purpose of this research is to evaluate the effects of L-glutamine as a therapy for sickle cell anemia and sickle ß0-thalassemia. as evaluated by the number of occurrences of sickle cell crises.
In this feasibility trial, the investigators will compare participants treated with montelukast and hydroxyurea to those treated with placebo and hydroxyurea for a total of 8 weeks.
A promising approach for the treatment of genetic diseases is called gene therapy. Gene therapy is a relatively new field of medicine that uses genetic material (mostly DNA) from the patient to treat his or her own disease. In gene therapy, the investigators introduce new genetic material in order to fix or replace a diseased gene, with the goal of curing the disease. The procedure is similar to a bone marrow transplant, in that the patient's malfunctioning blood stem cells are reduced or eliminated using chemotherapy, but it is different because instead of using a different person's (donor) blood stem cells for the transplant, the patient's own blood stem cells are given back after the new genetic material has been introduced into those cells. This approach has the advantage of eliminating any risk of Graft-Versus-Host Disease (GVHD), reducing the risk of graft rejection, and may also allow less chemotherapy to be utilized for the conditioning portion of the transplant procedure. The method used to fix or replace a diseased gene is called gene editing. A person's own cells are edited using a specialized biological medicine that has been formulated for use in human beings. Fetal hemoglobin (HbF) is a healthy, non-sickling kind of hemoglobin. Investigators have recently discovered a gene called BCL11A that is very important in the control of fetal hemoglobin expression. Increasing the expression of this gene in sickle cell patients could increase the amount of fetal hemoglobin while simultaneously reducing the amount of sickle hemoglobin in their blood, and therefore potentially cure the condition.
The purpose of this study is to determine the safety and clinical effects of SCD-101 when given to adults with sickle cell disease.
The purpose of this study is to evaluate the long-term safety and efficacy of EDIT-301 in participants with severe sickle cell disease (SCD) or transfusion-dependent β-thalassemia (TDT) who have received EDIT-301.
This clinical trial is a Phase 2 study that will evaluate the safety and clinical activity of etavopivat in patients with thalassemia or sickle cell disease and test how well etavopivat works to lower the number of red blood cell transfusions required and increase hemoglobin.
This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.
Study of IMR-687 in adult participants with sickle cell anemia (SCA) (homozygous HbSS or sickle-β0 thalassemia).
Background: Sickle cell disease (SCD) is an inherited disorder of the blood. SCD causes red blood cells (RBCs) to die early. This can lead to a shortage of healthy cells. SCD and other blood disorders can be managed with drugs or cured with a bone marrow transplant. Researchers want to know how long RBCs survive in people with SCD and other blood disorders before and after treatment compared to those who had a bone marrow transplant. Objective: To learn how long RBCs survive in the body in people with SCD and other blood disorders compared to those whose disease was cured with a bone marrow transplant. Eligibility: People aged 18 years or older with SCD or another inherited blood disorder. People whose SCD or blood disorder was cured with a bone marrow transplant are also needed. Design: Participants will be screened. They will have a physical exam with blood and urine tests. Participants will have about 7 tablespoons of blood drawn. In the lab, this blood will be mixed with a vitamin called biotin. Biotin sticks to the outside of RBCs. This process is called "biotin labeling of RBCs." The next day, the participant s own biotin-labeled RBCs will be returned to their bloodstream. Participants will return regularly to have smaller blood samples (about 2 teaspoons) drawn. These samples will be tested to detect the percentage of cells that have biotin labels. These visits may be every 2 weeks, 4 weeks, or some other interval. Participants will continue this schedule for up to 20 weeks or until biotin can no longer be detected....
The purpose of this study is to find out whether siplizumab is safe and effective for patients with SCD undergoing an allogeneic transplant and to prevent development of Graft versus Host Disease (GVHD) and graft failure. The main goals of this study are : * To determine if acute GVHD occurs and how severe the acute GVHD is in subjects receiving the study drug * To determine if graft failure occurs in subjects receiving the study drugs In this study, participants will receive 5 infusions of the study drug, siplizumab, while getting a stem cell transplant for SCD. Before siplizumab infusion, participants will be given medications to reduce the risks of allergic reaction to the drug.
Background: Sickle cell disease (SCD) is a genetic disease that causes the body to produce abnormal ( sickled ) red blood cells. SCD can cause anemia and life-threatening complications in the lungs, heart, kidney, and nerves. People with SCD are also at increased risk of forming blood clots in the veins and lungs, but the standard treatments for these clots can cause increased bleeding in people with SCD. Better treatments are needed. Objective: To test a drug (fostamatinib) in people with SCD. Eligibility: People aged 18 to 65 with SCD. Design: Participants will have 6 clinic visits over 12 weeks. Each visit will be 2 to 3 hours. Participants will be screened. They will have a physical exam with blood tests. They will tell the researchers about the medications they take. Fostamatinib is a tablet taken by mouth. Participants will take the drug at home, twice a day, for up to 6 weeks. Participants will have a clinic visit every 2 weeks while they are taking the drug. At each visit they will have a physical exam with blood tests. They will talk about any side effects the drug may be causing. If they are tolerating the drug well after the first 2 weeks, they may begin taking a higher dose. Participants will have a final visit 4 weeks after they stop taking the drug. They will have a physical exam and blood tests; they will be checked for any side effects of the drug.
Background: Sickle cell disease (SCD) is an inherited blood disorder. The disease affects the ability of red blood cells to carry oxygen; this in turn can injure organs including the heart, lungs, and kidneys. SCD can lead to serious illness and death. Treatments such as bone marrow transplants and gene therapies can cure SCD, but they are not widely available. Current drug treatments for SCD are not always effective. This natural history study will examine how a study drug (mitapivat) affects red blood cells in people with SCD. Objective: To learn how mitapivat affects red blood cells in people with SCD. Eligibility: People with SCD who are enrolled in the parent study, NIH protocol IRB001565-H. Design: Procedures for this study will be done during visits already scheduled for the parent study. Participants will have additional blood drawn during study visits. The additional amount will be about 3.5 teaspoons. Participants will undergo a test called near infrared spectroscopy (NIRS) up to 9 times. Probes will be placed on their skin. A blood pressure cuff will be placed on their arm. The cuff will be filled with air for up to 5 minutes and then released. Participants may be asked to breathe at a certain rate or to hold their breath during these measurements. NIRS measures oxygen levels, blood flow, and the makeup of skin and muscle. Researchers will draw additional information for this study from participants medical records.
The primary objective of this study is to evaluate a potential behavioral intervention (MED-Go app). To meet this objective, the researchers will conduct a pilot randomized controlled trial to test the feasibility and acceptability of MED-Go app in adolescents and young adults (AYA) with sickle cell disease (SCD). The long-term goal of this research is to promote medication adherence behavior and improve health outcomes in AYA with SCD.
This project addresses three important research questions. First, adolescents and young adults (AYA) with sickle cell disease (SCD) and their parents/caregivers will be engaged to inform the (1) domains of health-related quality of life (HRQOL) most important to them, (2) frequency at which they are willing to complete them, and (3) other procedures related to the use, uptake and effect of the HU-Go app as a tool to improve hydroxyurea (HU) adherence. Second, this study seeks to utilize novel modern mobile technology using a multi-functional personalized platform to improve adherence to HU and measure HRQOL in youth with SCD, using NIH-endorsed PROMIS® measures, based on a conceptual model with predefined behavioral targets and mediators. Third, we plan to assess HRQOL changes and identify modifiable behavioral strategies that could serve as surrogates or predictors for HU adherence. This real-time feedback might empower self-directed changes in behavior that could improve adherence to HU.
Beta-thalassemias and hemoglobinopathies are serious inherited blood diseases caused by abnormal or deficiency of beta A chains of hemoglobin, the protein in red blood cells which delivers oxygen throughout the body.The diseases are characterized by hemolytic anemia, organ damage, and early mortality without treatment. Increases in another type of (normal) hemoglobin, fetal globin (HbF), which is normally silenced in infancy, reduces anemia and morbidity. Even incremental augmentation of fetal globin is established to reduce red blood cell pathology, anemia, certain complications, and to improve survival. This trial will evaluate an oral drug discovered in a high throughput screen, which increases fetal globin protein (HbF and red blood cells expressing HbF)and messenger ribonucleic acid (mRNA) to high levels in anemic nonhuman primates and in transgenic mice. The study drug acts by suppressing 4 repressors of the fetal globin gene promoter in progenitor cells from patients. The drug has been used for 50 years in a combination product for different actions - to enhance half-life and reduce side effects of a different active drug- and is considered safe for long-term use. This trial will first evaluate 3 dose levels in small cohorts of nontransfused patients with beta thalassemia intermedia. The most active dose will then be evaluated in larger subject groups with beta thalassemia and other hemoglobinopathies, such as sickle cell disease.
The primary objectives of this prospective mixed-method interview study are to use semi-structured interviews in parents of sickle cell disease (SCD) patients to describe parental attitudes of research involving genomic sequencing, including concerns about participation and expectations from researchers and to use surveys to quantitatively measure genetic/genomic knowledge, trust in health care provider, and literacy/numeracy ability in parents of children with SCD and adolescents with SCD. Investigators hope to use the results of the planned surveys and interviews to reduce the risk of misunderstanding about DNA and genetic research and build strong relationships between SCD families and researchers in the future, and to design educational information and study materials that will help parents with children with SCD understand important details about DNA and genetic research.