36 Clinical Trials for Various Conditions
The overall purpose of this study is to obtain a better understanding of the biological response of red blood cells to sulforaphane contained in fresh broccoli sprouts that have been put through a blending process. This study will use commercially available fresh broccoli sprouts certified by Brassica Protection Products LLC (BroccoSprouts®). This product can also be purchased at some local grocery stores in the produce section. It is believed that NRF2, a transcription factor encoded by the NFE2L2 gene, plays a role in the regulation of defense against oxidative stress. The detrimental accelerated breakdown of sickle cell disease (SCD) red blood cells (SS RBC) is partially due to reduced anti-oxidative capacity. Previous analysis of SS RBC microRNAs revealed that a reduced level of NRF2, the master regulator of anti-oxidative stress capacity, contributes to reduced resistance to oxidative stress and increased hemolysis; NRF2 also induces fetal hemoglobin (HbF), which is known to prevent SS RBC sickling. First, erythroid progenitors from normal and SCD subjects will be tested ex-vivo to find out how sulforaphane, a natural NRF2 activator, affects the oxidative stress capacity, HbF expression, and microRNA expression of red cells. Second, a pilot clinical trial will be conducted to determine the safety and physiological effects of 3 weeks of daily consumption of broccoli sprout homogenate in a cohort of Hb SS/SB0 thalassemia adult SCD patients. During this study, subjects RBCs will be assayed for changes in anti-oxidative stress capacity and microRNA composition in mature SCD red blood cells.
This is a single-arm, mechanistic clinical trial to measure predictors of senescence and the in vivo survival of transfused red blood cells (RBCs) in individuals with sickle cell disease (SCD) receiving chronic transfusion therapy (CTT). Chronic transfusion in patients with SCD is a common treatment. The efficacy of RBC transfusion therapy to treat or prevent complications of SCD may be hampered by variable survival of the transfused donor RBC. The overall aim is to see how long RBC survive in SCD patients who are chronically transfused. When a study participant has a regular blood transfusion the researchers will label a small portion of the RBCs that are transfused with biotin. The participant will return at Day 1, weekly for 3 months and monthly for 3 months to measure how long those RBCs survive. An optional sub-study using INTERCEPT RBCs will mirror the main study but will use INTERCEPT RBCs that have biotinylated for 1 RBC unit.
The purpose of this study is to evaluate the performance of the Spectra Optia system red blood cell exchange (RBCx) protocols (exchange and depletion/exchange) in study participants with sickle cell disease.
The main purpose of this project is to cure patients with high risk Sickle cell disease and other red cell disorders including thalassemia and diamond-blackfan anemia by bone marrow transplantation. The patients enrolled in this study will be those who lack matched sibling donors and therefore have no other option but to undergo bone marrow transplantation using matched but unrelated bone marrow or umbilical cord blood from the national marrow donor program registry. Since bone marrow transplantation for these disorders using matched unrelated donors has two major problems i.e. engraftment, or , the process of new marrow being accepted and allowed to grow in the the patient; and graft-versus-host disease, or the process where the new marrow "rejects" the host or the patient, this study has been devised with methods to overcome these two problems and thus make transplantation from unrelated donors both successful in terms of engraftment and safe in terms of side effects, both acute and long term. In order to accomplish these two goals, two important things will be done. Firstly, patients will get three medicines which are considered reduced intensity because they are not known to cause the serious organ damage seen with conventional chemotherapy. These medicines, however, do cause intense immune suppression so these can cause increased infections. Secondly, in addition to transplantation of bone marrow from unrelated donors, patients will also transplanted with mesenchymal stromal cells derived from the bone marrow of their parents. Mesenchymal stromal cells are adult stem cells that are normally found in the bone marrow and are thought to create the right background for the blood cells to grow. They have been shown in many animal and human studies to improve engraftment. In addition, they have a special property by which they prevent and are now even considered to treat graft versus host disease. Therefore, by using a reduced intensity chemotherapy regimen before transplant and transplanting mesenchymal stromal cells, we hope to improve engraftment while at the same time decrease the potential for severe side effects associated with a conventional transplant which uses extremely high doses of chemotherapy.
The SCD-CARRE trial is a Phase 3, prospective, randomized, multicenter, controlled, parallel two-arm study aimed to determine if automated exchange blood transfusion and standard of care administered to high mortality risk adult SCD patients reduces the total number of episodes of clinical worsening of SCD requiring acute health care encounters (non-elective infusion center/ER/hospital visits) or resulting in death over 12 months as compared with standard of care.
Background: Some people with the same disorder on a genetic level have more complications than others. Researchers want to look for a link between the PKLR gene and sickle cell disease (SCD) symptoms. The PKLR gene helps create a protein, called pyruvate kinase that is essential in normal functioning of the red blood cell. Differences in the PKLR gene, called genetic variants, may cause some changes in the pyruvate kinase protein and other proteins, that can affect functioning of the red blood cell adding to the effect of SCD. Researchers can study these differences by looking at DNA (the material that determines inherited characteristics). Objective: To study how the PKLR gene affects sickle cell disease. Eligibility: Adults ages 18-80 of African descent. They may have sickle cell disease or not. They must not have had a transfusion recently or have a known deficiency of pyruvate kinase. They cannot be pregnant. Design: Participants will be screened with questions. Participants will have blood drawn by needle in an arm vein. The blood will be genetically tested. Not much is known about how genes affect SCD, so the test results will not be shared with participants or their doctors. ...
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....
A phase III, multi-center, randomized, placebo-controlled, double-blind study to assess efficacy and safety of crizanlizumab (5 mg/kg) versus placebo, with or without hydroxyurea/hydroxycarbamide therapy, in adolescent and adult Sickle Cell Disease patients with frequent vaso-occlusive crises.
This study is an open-label study to evaluate the safety of long-term administration of inclacumab in participants with sickle cell disease (SCD). Participants in this study will have completed a prior study of inclacumab.
Red Blood Cell - IMProving trAnsfusions for Chronically Transfused recipients (RBC-IMPACT) is an observational cohort study to assess donor, component, and recipient factors that contribute to RBC efficacy in chronically and episodically transfused patients. The objective of the study is to determine how specific genetic and non-genetic factors in donors and recipients may impact RBC survival after transfusion - in short, what factors on both the donor and recipient side may improve the efficacy of the transfusion.
This Phase 3 study will assess the safety and efficacy of inclacumab, a P-selectin inhibitor, in reducing the frequency of vaso-occlusive crises (VOCs) in approximately 240 adult and adolescent participants (≥ 12 years of age) with sickle cell disease (SCD). Participants will be randomized to receive inclacumab or placebo.
This Phase 3 study will assess the safety and efficacy of a single dose of inclacumab, a P-selectin inhibitor, for a vaso-occlusive crisis (VOC) after an index VOC in participants with sickle cell disease (SCD). Participants will be randomized to receive either inclacumab or placebo.
Background: Sickle cell disease (SCD) is a disorder that causes episodes of acute pain and progressive organ damage. Ways to manage SCD have evolved slowly. Treatments do not always work. Researchers want to see if a drug called mitapivat can help people with SCD. Objective: To test the long-term tolerability and safety of mitapivat (or AG-348) in people with SCD. Eligibility: Adults age 18-70 with SCD who took part in and benefited from NIH study #19H0097. Design: Participants will be screened with a medical history and physical exam. They will give a blood sample. They will have an electrocardiogram to test heart function. Participants will repeat some of the screening tests during the study. Participants will complete 6-minute walk tests to measure mobility and function. They will have transthoracic echocardiograms to measure heart and lung function. They will have dual-energy X-ray absorptiometry scans to measure bone health. They will complete online questionnaires that measure their overall health and well-being. Participants will take the study drug in the form of a tablet twice a day. Participants will keep a study diary. They will record any symptoms they may have. Participation will last for about 54 weeks. After 48 weeks, participants can either keep taking the study drug for 48 more weeks or be tapered off of the study drug to complete the study. Those who are on the study for 1 year will have 10 study visits. Those who are on the study for 2 years will have 14 study visits.
Background: Sickle Cell Disease (SCD) is an inherited blood disorder. People with SCD have abnormal hemoglobin in their red blood cells. Researchers are investigating the safety and efficacy of an investigational medicine called AG-348 (mitapivat sulfate) to determine if it will help people with SCD. Objective: To test the tolerability and safety of AG-348 in people with SCD. Eligibility: People ages 18 and older with SCD. Design: Participants will have 8 visits over approximately 14 weeks. At the first visit participants will be screened with a medical history, a physical exam, blood and urine testing, and an EKG. During the following 5 visits, participants will stay at the clinic for 1 night each. Participants will take study drug in increasing doses up to visit 6, after which the drug will be tapered off. All visits will include physical exam, blood, and urine tests. The last visit will occur 4 weeks after stopping the drug. Participants will provide DNA from the blood samples they provide. The DNA will be tested for an inherited gene that can cause differences in response to the study drug. Researchers may also test other genes to see if they can find any genes that interact with SCD.
The purpose of this study is to compare the efficacy and safety of 2 doses of crizanlizumab (5.0 mg/kg and 7.5 mg/kg) versus placebo in adolescent and adult sickle cell disease (SCD) patients with history of vaso-occlusive crisis (VOC) leading to healthcare visit.
Propanolol is a beta blocker which has been found to inhibit the ability of epinephrine to upregulate sickle red cell adhesion to laminin and endothelial cells in vitro. The purpose of this pilot study is to administer one dose of propanolol to children with sickle cell disease and to measure pre and post dose red cell adhesion. The hypothesis is that a single dose of propanolol will decrease red cell adhesion to laminin and endothelial cells as compared to baseline.
The purpose of this study is to determine the effects of transfusion of fresh and stored blood on patients. The investigators hope to test: * whether a similar effect (older stored blood is associated with worse outcomes) is seen in chronically transfused patients with hemoglobinopathies. This patient population will also allow the investigators to test whether iron- chelation therapy is beneficial in this setting. * whether washing or cryopreserving the red blood cells has any effect on this outcome. These findings may explain the immunomodulatory effects of older stored blood in patients and will help us develop safer transfusion products for patients.
Background: * 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. Objectives: - To test the safety and effectiveness of decitabine in increasing fetal hemoglobin levels and improving the symptoms of sickle cell disease. Eligibility: - 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. Design: * 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.
Packed red blood cell units destined for transfusion can be stored for up to 42 days prior to transfusion based on Food and Drug Administration (FDA) guidelines. Recent studies suggest that certain patients transfused with blood stored for longer duration have poorer outcomes than patients transfused fresher blood. The investigators' hypothesis is that the delivery of an immediate and substantial load of hemoglobin-associated iron from a stored unit of blood leads to changes that explain the differences in outcome between patients transfused old versus fresh blood. The investigators propose to test this hypothesis in humans by transfusing an individual's own blood, both fresh and after storage, and comparing levels of various outcome measures.
The purpose of this study is to determine the benefits as well as side effects of giving drugs called dipyridamole and magnesium to patients with sickle cell anemia (SCA).
This is an open-label, non-randomized, multi-center trial designed to provide expanded access of deferasirox to patients with congenital disorders of red blood cells and chronic iron overload from blood transfusions who cannot adequately be treated with locally approved iron chelators.
This multicenter prospective study seeks to determine if daratumumab given, prior to HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus, can prevent pure red blood cell aplasia with an acceptable safety profile in patients with anti-donor red blood cell antibodies, achieving an event-free survival similar to transplanted patients without such antibodies.
Background: Sickle cell disease (SCD) is an inherited blood disorder. It results from a single genetic change (mutation) in red blood cells (RBCs). RBCs are the cells that carry oxygen to the body. In people with SCD, some RBCs are abnormal and die early. This leaves a shortage of healthy RBCs. Researchers want to learn more about how long RBCs live in the human body. Objective: To study how long RBCs live in people with and without SCD. Eligibility: People age 18 and older who either have SCD, had SCD but were cured with a bone marrow transplant, have the sickle cell trait (SCT), or are a healthy volunteer without SCD or SCT Design: Participants will be screened with a medical history and physical exam. They will give a blood sample. Participants will have a small amount of blood drawn from a vein. In the laboratory, the blood will be mixed with a vitamin called biotin. Biotin sticks to the outside of RBCs without changing their function, shape, or overall lifetime. This process is known as biotin labeling of RBCs. The biotin labeled RBCs will be returned to the participant via vein injection. Participants will give frequent blood samples. Their RBCs will be studied to see how many biotin labeled RBCs remain over time. This shows how long the RBCs live. Participants will give blood samples until no biotin labeled RBCs can be detected. During the study visits, participants will report any major changes to their health. Participation lasts for up to 6 months.
This is a pilot study to evaluate the feasibility and safety of providing RH genotype matched D+ Red Blood Cells (RBCs) to chronically transfused patients with sickle cell disease (SCD) who type D+ but have formed anti-D and are currently transfused with D- RBC (Red Blood Cell) units.
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.
This study will examine the effects of granulocyte colony-stimulating factor (G-CSF) on bone marrow stem cells in healthy volunteers with sickle cell trait and determine if cells collected for transplantation from donors with sickle cell trait require special handling. Stem cells, which the bone marrow produces, are responsible for making all the different kinds of blood cells. They are the cells used in bone marrow, or stem cell, transplantation. The drug G-CSF, which is a naturally occurring hormone, causes stem cells to mobilize-that is, to be released from the bone marrow and enter the blood stream. This drug is given to stem cell donors to increase the amount of cells that can be collected. Stem cell donors for patients with sickle cell disease are often healthy siblings of the patient who have a matching bone marrow type. Some siblings carry the sickle cell trait, however, and, even though they do not have sickle cell disease and their blood and bone marrow are normal, it is not known how their cells will react to G-CSF stimulation. Nor is it known if their stem cells require special methods of removal, processing or storing. Healthy volunteers 18 years or older with sickle cell trait who have no history of sickle cell disease and no known medical problems may be eligible for this study. Participants will have a medical history and physical examination, including blood tests and urinalysis. They will receive injections of G-CSF under the skin once a day for 5 days. On the fifth day, stem cells will be collected through leukapheresis. In this procedure, whole blood is drawn from an arm vein, similar to donating whole blood. The blood then circulates through a cell separator machine, the stem cells are removed, and the rest of the blood is transfused back to the donor through a vein in the other arm. The information gained from this study will be used to ensure the safety of stem cell donors with sickle cell trait and to better prepare stem cells for transplantation in sickle cell patients.
This study will address if red blood cells transfused to a sickle cell patient from a donor with a glucose-6-phosphate-dehydrogenase (G6PD) enzyme deficiency have a different lifespan as measured by the percentage of red blood cells that survive post-transfusion compared to red blood cells transfused to a sickle cell patient from a donor without a G6PD enzyme deficiency.
The investigators hypothesize that increasing plasma nitrite using dietary nitrate will improve platelet function and red cell deformability and decrease MCHC in patients with sickle cell disease. The investigators will test this hypothesis through administration of daily intake of beetroot juice (Unbeetable - Performance Drink) to patients with sickle cell disease for 28 days. The investigators will evaluate the safety of daily beet root juice intake in patients with sickle cell disease. In addition, the investigators will measure MCHC, red cell deformability, and platelet function (activation and aggregation) in response to daily intake of beet root juice in this patient population.
Background: - Some people with sickle cell disease have different health problems than others. This may be related to how easily and frequently the red blood cells break apart in the blood. Researchers want to test breath and blood samples from people with sickle cell disease to look for very small amounts of carbon monoxide, which is produced when red blood cells break apart. They will compare these results with breath samples from healthy volunteers. Studying different levels of carbon monoxide may help predict what health problems a person with sickle cell disease may get. It may also provide more information on possible treatments. Objectives: - To study breath carbon monoxide levels and their possible relation to the severity of sickle cell disease. Eligibility: * Individuals at least 18 years of age with sickle cell disease. * Healthy volunteers who are matched for age, sex, and race with the sickle cell disease group. Design: * Participants will be screened with a medical history. * Participants with sickle cell disease will provide a blood sample and have a heart function test. They will also breathe into a bag to provide an exhaled breath sample. * Healthy volunteers will provide an exhaled breath sample. * No treatment or care will be provided as part of this study.
In this prospective observational trial, participants with chronic hemolysis will be assessed with echocardiogram for elevated tricuspid jet velocity and other evidence of pulmonary hypertension. Participants will have laboratory studies evaluating: severity of hemolysis, splenic function, inflammation, endothelial dysfunction, and hypercoagulability. There will be 3 main categories of participants enrolled in this study: (1) pediatric participants with severe sickle cell disease (SCD) (HbSS, HbS/β° thalassemia ) who are not receiving treatment (e.g., hydroxyurea or chronic transfusions); (2) pediatric participants with other forms of SCD or severe SCD (HbSS, HbS/β° thalassemia) patients being treated with hydroxyurea or chronic transfusions; and (3) pediatric and adult participants with other non-sickling hematological disorders.