Clinical Research Directory

Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease

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.

A Long-term Follow-up Study in Participants Who Received CTX001

This is a multi-site, open- label rollover study to evaluate the long-term safety and efficacy of CTX001 in pediatric and adult participants who received CTX001 in parent studies 111 (NCT03655678) 141 (NCT05356195) or 161 (NCT05477563) (transfusion-dependent β-thalassemia \[TDT\] studies) or Study 121 (NCT03745287) or 151 (NCT05329649) or 161(NCT05477563) (severe sickle cell disease \[SCD\] studies).

Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease

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.

Addition of JSP191 (C-kit Antibody) to Nonmyeloablative Hematopoietic Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia

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.

Blood Sampling for Research Related to Sickle Cell Disease

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.

Serial Assessment of Fertility Experiences

The SAFE study is a long-term research project that watches people with sickle cell anemia (SCA) over time. The main goal is to see how a medicine called hydroxyurea affects their growth, puberty, and ability to have children. A second goal is to see how hydroxyurea affects pregnancy outcomes, by comparing people who take the medicine to those who don't.

Alendronate for Osteonecrosis in Adults With Sickle Cell Disease

A prospective, single-arm, intervention study of oral alendronate in adults with sickle cell disease and osteonecrosis

Verifying Antibodies After Live Immunization Delivery (VALID): A Study of Measles Vaccine Immunogenicity in Children With Sickle Cell Disease

The goal of this study is to learn if infants with sickle cell disease (SCD) develop adequate protection after measles vaccines. (not looking at any prolonged duration)

Efficacy and Safety of SIL-8301 for Control of Hemolysis in a Uniform Sickle Cell Disease Endotype

SIL-8301 (senicapoc) is being developed for the chronic treatment of patients with sickle cell disease in both adults and children. The purpose of this study is to compare the effects of senicapoc to placebo in patients with sickle cell disease that have had fewer than 2 acute sickle-related painful crises per year over the preceding 2 years, and have a predominantly hemolytic phenotype, defined as presence or history of at least one hemolytic complication and a baseline Hb of 9 g/dL or less, despite receiving hydroxyurea (an oral drug used for treatment of sickle cell disease) as standard of care. Participants will take senicapoc or matching placebo daily and continue on hydroxyurea as prescribed for up to 24 weeks.

Stroke Prevention in Young Adults With Sickle Cell Anemia

Sickle cell disease (SCD) is the most common genetic disease, affecting about 25 million people worldwide. Approximately 150,000 Nigerian children are born each year with sickle cell disease (SCD), making it the country with the largest burden of SCD in the world. Recent advancements in care for children with SCA have translated into improved survival of children in both high and low-resource settings. However, more complications of SCD are seen in those who survive to adulthood. Silent cerebral infarcts (SCI) and strokes are among the most devastating complications of SCD, affecting 40% and 10% of children, respectively. The overall goal of this study is to extend the Investigator's successful capacity-building effort in the assessment of neurological morbidity in children with SCD living in northern Nigeria (Kano) to young adults with SCD living in the same region. About 50% of all adults with SCD live in Nigeria. Despite the high prevalence of SCD in Africa, the neurological morbidity is not well characterized, limiting opportunities for primary and secondary stroke prevention strategies. At least 50% of young adults with sickle cell anemia (SCA), the most severe form of the disease, will have SCIs and an estimated 10% will have strokes, based on studies in high-resource settings. In high-resource settings, screening for abnormal transcranial Doppler (TCD) velocities in children with SCA, coupled with regular blood transfusion has resulted in a 92% reduction of relative risk for strokes. Despite this effective strategy, regular blood transfusion therapy does not seem sustainable in sub-Saharan Africa due to shortages and the risk of transfusion transmissible infections. Additionally, there is a lack of evidence-based stroke prevention strategies in young adults with SCA, either in the high-income or in low-resource settings. Based on the foregoing, the Investigators propose to determine the prevalence of neurological injury (overt stroke, transient ischemic attacks, and silent cerebral infarcts) in young adults at the transition age from 16-25 years. The Investigators will also, for the first time, assess conventional risk factors of stroke in the general population to determine whether a different prevention strategy is required to reduce the incidence of neurological injury in this high-risk population.

Awake Prone Positioning for Severe Acute Chest Syndrome

Acute chest syndrome (ACS) is the leading cause of admission to intensive care and the leading cause of death in patients with sickle cell disease. Irrespective of the cause of ACS, there is an heterogeneity in pulmonary ventilation/perfusion ratios, leading to worsening of the disease. Efficiency of awake prone positioning (APP) in acute respiratory failure (ARF) was particularly highlighted during the COVID-19 pandemic. Several physiological factors contribute to this benefit including an improvement in ventilatory drive and gas exchange. The investigator hypothesize that APP could lead to clinical improvement in ACS in terms of oxygenation and ventilatory drive, by improving the heterogeneity of ventilation

Sickle Cell Disease (SCD) Bone Pain Study

A prospective study to determine how low bone mineral density and/or vertebral compression fractures associate with pain in adults with sickle cell disease

T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias

The purpose of this study is to evaluate what effect, if any, mismatched unrelated volunteer donor and/or haploidentical related donor stem cell transplant may have on severe sickle cell disease and other transfusion dependent anemias. By using mismatched unrelated volunteer donor and/or haploidentical related donor stem cells, this study will increase the number of patients who can undergo a stem cell transplant for their specified disease. Additionally, using a T-cell depleted approach should reduce the incidence of graft-versus-host disease which would otherwise be increased in a mismatched transplant setting.

Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation

The purpose of this research study is to document and understand the effects of hydroxyurea exposure for women with SCD and their babies, during both gestation and lactation.

Pressure Pain Tolerance in Relation to Balance and Strength in Children

Sickle cell disease (SCD) is the most frequent life-threatening genetic hemoglobinopathy in the world and occurs due to the synthesis of abnormal hemoglobin S (HbS).Cells with sickle cell hemoglobin are stiff and sticky. When they lose their oxygen, they form into the shape of a sickle or crescent. This can cause pain and tissue damage. Significant decrease in exercise capacity was seen in sickle cell anemic children. In the absence of a guidelines that can guide the prescription of exercise in SCD children. This study is a step for determine the forms of prescription of pain on the balance and muscle strength to build up in future studies a safety of physical exercises for children with sickle cell anemia and improve their functional abilities.

Haploidentical PBMC Transplant for Severe Congenital Anemias

Background: Bone marrow transplantation (BMT), which involves transplanting a donor's marrow stem cells, is capable of curing some congenital anemias. BMT usually involves high-intensity treatment with chemotherapy and radiation to kill abnormal cells, which affects all systems of the body. People with anemias often have damage to other organs such as the kidneys, which can be further damaged by the chemotherapy. Only approximately 20 percent of patients have a full-matched donor, making treatment for many people with anemias unavailable. However, 90 percent of patients may have a half-matched donor, but using a half-matched donor increases the toxicity of BMT. Objectives: To determine if a research BMT with half-matched donor cells, low-intensity radiation, immunosuppressant drugs, and no chemotherapy will be effective in patients with sickle cell disease and Beta-thalassemia. To determine the effectiveness of cyclophosphamide, an immunosuppressant drug, in preventing rejection of the donor cells. Eligibility: Recipients are individuals at least 18 years of age who have been diagnosed with sickle cell disease and Beta-thalassemia, and who have a family member who is a haploidentical (i.e., half match) tissue match. Donors are healthy individuals between the ages of 2 and 80 who are found to be suitable donors. Design: Donors will undergo apheresis, which involves withdrawing blood from one arm vein, passing it through a machine that removes bone marrow stem cells, and returning the remaining blood through the vein in the other arm. Donors will receive a drug that causes the stem cells to be released into the bloodstream prior to the apheresis procedure. Recipients will undergo routine physical and laboratory examinations, including bone marrow sampling at the beginning of the study. After transplantation, physical and laboratory examinations will occur on a weekly or twice weekly basis at the outpatient clinic. Recipients will be examined every 6 months starting 100 days posttransplant for 5 years. Recipients will receive low-dose radiation in two treatments 1 and 2 days before the transplant. They will also be given immunosuppressant therapy with alemtuzumab and sirolimus. Another immunosuppressant drug, cyclophosphamide, will be given in the future as needed to subsets of the recipients to prevent rejection of donor cells. Recipients will receive the donor stem cells through a previously inserted central line. The process takes up to 8 hours. Recipients will receive blood transfusions as necessary to prevent anemia and bleeding during the posttransplant period. They may also receive intravenous antibiotics to prevent infection.

A Trial to Assess Haploidentical T-depleted Stem Cell Transplantation in Patients With SCD

HSCT is currently the only curative option for SCD but less than 20% of SCD patients have a MD donor available. So far, all curative approaches beyond a MSD HSCT at young age are non-satisfactory. With the lack of a suitable donor for the vast majority of patients, the major question of this trial is, if a haploidentical αß/CD19+ T-cell depleted HSCT can be a valid alternative to a MSD HSCT. The main challenge in non-malignant diseases is to offer a safe and GvHD-free HSCT without rejection.