Active clinical trials for "Anemia, Sickle Cell"

Sickle cell disease (SCD) is one of the most common genetic diseases in the world. In North America, an estimated 2600 babies are born with SCD each year1, and approximately 70,000 to 100,000 individuals of all ages are affected in the United States2. The clinical manifestations of SCD include acute events, such as recurrent debilitating painful crises, as well as life-threatening pulmonary, cardiovascular, renal, and neurologic complications. The only established curative treatment for SCD patients is allogeneic hematopoietic stem cell transplant (HSCT). Unfortunately, access to this intervention is limited by availability of suitable matched donors, and HSCT is associated with significant morbidity and mortality. For patients who cannot undergo HSCT, treatment of SCD has been limited to one FDA-approved medication, hydroxyurea, and supportive symptomatic care. After decades with very few novel therapeutic options for SCD patients, autologous cell-based genetic therapies, including lentiviral-based gene therapy as well as gene editing, now offer the possibility of innovative curative approaches for patients lacking a matched donor for hematopoietic stem cell transplantation. Gene therapy for sickle cell disease is increasingly promising, and there are currently open clinical trials at several centers that employ a gene addition strategy. Options for autologous HSC collection include bone marrow harvest or peripheral blood HSC mobilization. Bone marrow (BM) harvest is an invasive procedure requiring anesthesia, which is associated with sickle cell-related morbidities, and may not achieve goal CD34+ cell dose, necessitating repeated procedures scheduled over multiple months. In most gene therapy trials, HSCs are obtained through peripheral collection after mobilization with granulocyte colony-stimulating factor (G-CSF) followed by peripheral blood (PB) apheresis. However, this approach is contraindicated in SCD because G-CSF has been reported to cause severe adverse effects in sickle cell patients. Even with doses sometimes smaller than standard, G-CSF has been shown to result in vaso-occlusive crises, severe acute chest syndrome, and in one report, massive splenomegaly and death. Alternative options for mobilization are needed. Plerixafor has been compared to G-CSF in a sickle cell mouse model, and results showed effective mobilization of HSC subsets, without neutrophil or endothelial activation, and with lower total WBC and neutrophil counts compared to G-CSF-treated mice. Plerixafor use has not yet been documented in sickle cell patients. One other trial is currently open to test plerixafor in SCD patients (NCT02193191) but no results have yet been reported. Based on pre-clinical data, the mechanism of action of plerixafor, as well strategies the investigator will employ to mitigate risk, the investigator anticipates that it will be well-tolerated in the SCD patient population.

The aim of the present study is comparing the effectiveness of different treatment regimens for investigating the therapeutic potential for each one in management of Vaso-occlusive pain in pediatric sickle cell disease. In addition, investigators apply the Cost-effectiveness analysis (CEA) as a form of economic analysis that compares the relative costs and outcomes (effects) for different treatment regimens on vaso-occlusive painful crisis.

This study will assess the safety of changing pain medications (opioids) adult sickle cell patients take to another type of medication therapy (buprenorphine). Patients will be asked questions about their quality of life. Other tools for assessment will also be administered.

This first in human study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and food effect of GBT021601, a hemoglobin S (HbS) polymerization inhibitor, in healthy participants.

This study is a pilot, open-label, single-arm study to evaluate the effect of the sickle cell medication voxelotor on exercise capacity, as measured by cardiopulmonary exercise testing (CPET) in patients 12 years of age and older with sickle cell anemia (SCA).

The proposed research is designed to test the global hypothesis that inhaled corticosteroids (ICS), a therapy developed to treat asthma, will prevent vasoocclusive painful episodes in adults with Sickle Cell Disease (SCD) who wheeze, but do not meet criteria for a diagnosis of asthma. The specific aims of this proposal are 1) Conduct a feasibility study - a randomized controlled trial of ICS for adults with SCD who do not meet criteria for a diagnosis of asthma but report recurrent cough or wheezing, 2) Measure the effects of ICS on biological correlates of pulmonary inflammation (as determined by exhaled nitric oxide) and vascular injury (as determined by sVCAM) in SCD, and 3) Compare properties of traditional and Bayesian adaptive clinical trial design for therapeutic trials in SCD in preparation for designing a definitive trial of ICS. These aims have the potential to 1) change the standard of care for individuals with SCD and recurrent cough or wheeze, 2) provide insight into the pathogenesis of non-asthmatic wheezing in SCD and its response to treatment, 3) explore the suitability of innovative clinical trial designs to overcome the challenges that have hindered therapeutic innovation for SCD.

Multiple studies have shown that hydroxyurea has clinical efficacy in preventing acute painful episodes and reducing the need for blood transfusions in children with sickle cell anemia (SCA), but no study has been conducted in malaria endemic regions of sub-Saharan Africa, the areas with the most children with SCA. The primary goal of this study is to investigate the safety and efficacy of hydroxyurea for children with SCA in a malaria endemic region within sub-Saharan Africa.

The purposes of this study are to observe if oral tetrahydrouridine and decitabine can increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to monitor how patient's bodies react to oral tetrahydrouridine and decitabine.

The purpose of this study is to determine the effectiveness of A 001 infusion in preventing acute chest syndrome in sickle cell disease (SCD) subjects with vaso-occlusive crisis, fever, and elevated serum C-reactive protein (CRP).

Background: - Chronic leg ulcers are a complication of many blood disorders such as sickle cell disease, thalassemia, and other red blood cell disorders. In these disorders, red blood cells break down earlier than normal, which researchers suspect may cause or contribute to the development of leg ulcers; however, the exact cause is unknown, and current therapies are not very effective. Researchers are interested in determining if a research cream made with sodium nitrite, a substance that is known to increase blood flow by dilating blood vessels, may speed up the healing of skin ulcers. Objectives: - To evaluate the safety and effectiveness of topical sodium nitrite cream as a treatment for chronic leg ulcers in individuals with sickle cell disease or other red blood cell disorders. Eligibility: - Individuals at least 18 years of age who have sickle cell disease or another red cell disorder and have had a leg ulcer for more than 4 weeks. Design: Participants will be screened with a physical examination, medical history, blood tests, and an examination of the ulcer, including x-ray of the leg(s) with the ulcer and swabs from the wound. Participants will be scheduled for a 5-day inpatient stay at the Clinical Center, with the following procedures: Days 1 and 2: Participants will have blood draws, a wound assessment, ultrasound of the affected leg, imaging studies (magnetic resonance imaging and infrared photography), thermo-patch application to monitor temperature changes, measurements of blood flow in the skin, and questionnaires about pain and quality of life. An optional skin biopsy may also be conducted with samples taken near the skin ulcer Day 3: Participants will have one ulcer treated with the topical cream. Frequent blood draws will be conducted before application and then regularly for up to 6 hours after application of the cream. Thirty minutes after the research cream is applied, participants will have imaging studies of the treated leg and measurements of pain levels and blood flow. Day 4: Participants will have a blood draw and temperature recordings taken. Day 5: Participants will have the research cream applied and the same imaging studies as before, and will be discharged for care at home. For the following 3 weeks, participants will come to the clinical center twice a week to have the research cream applied to the leg ulcer and tests performed by the study researchers. For the fourth and final week, participants will return for additional cream treatment sessions, imaging studies, blood draws, and other tests as directed by the study researchers. Study participation will end in the following week (week 5). Subjects will come for a final visit one month after the end of the study.