Clinical Research Directory

A Study to Evaluate BMS-986470 in Healthy Volunteers and Participants With Sickle Cell Disease

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, pH and food effect, and preliminary efficacy of BMS-986470 in healthy volunteers and participants with sickle cell disease.

Telemedicine for Children With Sickle Cell Disease

The purpose of this study is to learn more about how the use of two different types of telemedicine (distance medical care) can address barriers to receiving comprehensive sickle cell care, and whether care can be improved. Aim 1: Adapt two telemedicine models (i.e., hub-and-spoke; direct-to-consumer) for use with children with SCD using caregiver input from our preliminary K12 work. Aim 2: Demonstrate the feasibility of the telemedicine models developed in Aim 1 as the models undergo successive stakeholder refinement during use in actual clinical care. Aim 3: Evaluate the effectiveness of the refined models from Aim 2 in a pre/post study by assessing (a) process of care measures, (b) provider satisfaction, (c) caregiver/patient-centered outcomes, and (d) clinical outcomes and healthcare utilization.

A Blood Stem Cell Transplant for Sickle Cell Disease

Blood stem cells can produce red blood cells (which carry oxygen), white blood cells of the immune system (which fight infections) and platelets (which help the blood clot). Patients with sickle cell disease produce abnormal red blood cells. A blood stem cell transplant from a donor is a treatment option for patients with severe sickle cell disease. The donor can be healthy or have the sickle cell trait. The blood stem cell transplant will be given to the patient as an intravenous infusion (IV). The donor blood stem cells will then make normal red blood cells - as well as other types of blood cells - in the patient. When blood cells from two people co-exist in the patient, this is called mixed chimerism. Most children are successfully treated with blood stem cells from a sibling (brother/sister) who completely shares their tissue type (full-matched donor). However, transplant is not an option for patients who (1) have serious medical problems, and/or (2) do not have a full-matched donor. Most patients will have a relative who shares half of their tissue type (e.g. parent, child, and brother/sister) and can be a donor (half-matched or haploidentical donor). Adult patients with severe sickle cell disease were successfully treated with a half-matched transplant in a clinical study. Researchers would like to make half-matched transplant an option for more patients by (1) improving transplant success and (2) reducing transplanted-related complications. This research transplant is being tested in this Pilot study for the first time. It is different from a standard transplant because: 1. Half-matched related donors will be used, and 2. A new combination of drugs (chemotherapy) that does not completely wipe out the bone marrow cells (non-myeloablative treatment) will be used to prepare the patient for transplant, and 3. Most of the donor CD4+ T cells (a type of immune cells) will be removed (depleted) before giving the blood stem cell transplant to the patient to improve transplant outcomes. It is hoped that the research transplant: 1. Will reverse sickle cell disease and improve patient quality of life, 2. Will reduce side effects and help the patient recover faster from the transplant, 3. Help the patient keep the transplant longer and 4. Reduce serious transplant-related complications.

Epidemiology of Silent and Overt Strokes in Sickle Cell Disease

Sickle Cell Disease (SCD) is a rare disease occurring in an estimated 100,000 individuals, often poor and underserved, in the US. Silent and overt strokes contribute significantly to morbidity in adults with SCD, resulting in functional impairment, challenges with school and job performance, and premature death. Five NIH-funded randomized controlled trials have identified therapies to prevent silent and overt strokes in children with SCD, including monthly blood transfusion therapy (for preventing initial and recurrent strokes) and hydroxyurea (for preventing initial strokes). Despite the observation that at least 99% of children with SCD in high-income countries reach adulthood, and approximately 60% of adults will experience one or more strokes (\~50% with silent strokes and \~10% with overt strokes), no stroke trials have established therapeutic approaches for adults with SCD. For adults with SCD, inadequate evidence-based guidelines exist for secondary stroke prevention strategies. Applying stroke prevention strategies in children may not be effective for stroke prevention in adults with SCD, particularly given the high rate of co-morbidities. Identifying subgroups of adults with SCD and higher incidence coupled with the contribution of established stroke risk factors in the general population (smoking, diabetes, obesity, renal disease) will provide the requisite data required for the first-ever phase III clinical trials focused on secondary stroke prevention in adults.

A Safety, Efficacy, and Pharmacokinetic (PK) Study of HBI-002, an Oral Carbon Monoxide (CO) Therapeutic, in Subjects With Sickle Cell Disease (SCD)

This is a multi-center, open label Phase 2a clinical trial in subjects with sickle cell disease to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of HBI-002, an orally administered liquid containing carbon monoxide (CO), with doses daily for 14 days.

Metabolic and Hemodynamic Reserve in Pediatric SCA

The purpose of this research study is to better understand how blood flow and metabolism change can influence brain development in the early decades of life. SCA participants and healthy controls are age and sex-matched for comparison. Within the SCA cohort, children with infarcts may have thinner cortices than those without, reflecting a greater loss. The investigators will examine brain blood flow and metabolism using magnetic resonance imaging (MRI). The brain's blood vessels expand and constrict to regulate blood flow based on the brain's needs. The amount of expanding and contracting the blood vessels may vary by age. The brain's blood flow changes in small ways during everyday activities, such exercise, deep concentration, or normal brain growth. Significant illness or psychological stress may increase the brain's metabolic demand or cause other bigger changes in blood flow. If blood vessels are not able to expand to give more blood flow when metabolic demand is high, the brain may not get all of the oxygen it needs. In extreme circumstances, if the brain is unable to get enough oxygen for a long time, a stroke may occur. Sometimes small strokes occur without other noticeable changes and are only detectable on an MRI. These are sometimes called "silent strokes." In less extreme circumstances, not having a full oxygen supply may cause the brain to grow and develop more slowly than when it has a full supply. One way to test the ability of blood vessels to expand is by measuring blood flow while breathing in carbon dioxide. Carbon dioxide causes blood vessels in the brain to dilate without increasing brain metabolism. During this study participants may be asked to undergo a blood draw, MRI, cognitive assessments, and brief questionnaires. The study team will use a special mask to control the amount of carbon dioxide the participants breathe in.

Therapeutic Response Evaluation and Adherence Trial (TREAT)

The primary objectives of this prospective study of hydroxyurea for children with sickle cell anemia are 1) Develop and prospectively evaluate a population pharmacokinetic/pharmacodynamics model to predict the maximum tolerated dose (MTD); 2) Identify urine biomarkers of hydroxyurea adherence using a novel metabolomics approach; 3) Identify pharmacogenomics modifiers of hydroxyurea MTD; and 4) Longitudinal monitoring of the effect of hydroxyurea upon organ function and quality of life.

A Socio-ecological Approach for Improving Self-management in Adolescents With SCD

The goal of this clinical trial is to evaluate the impact of SCThrive (a behavioral self-management intervention) on patient activation, self-management behaviors, daily functioning, and emergency room visits in 260 adolescents and young adults with sickle cell disease (SCD) ages 13-21 receiving care at 1 of 4 pediatric SCD clinics. The main question\[s\]it aims to answer are: * Does SCThrive improve patient activation? * Does SCThrive improve self-management behaviors, daily functioning, and decrease emergency room visits? * Are any improvements maintained 3 months after treatment? Participants will complete self-management related surveys before, after, and 3 months following their participation in an 8- week, virtual group intervention with an accompanying mobile app (SCThrive). Researchers will compare outcomes for participants who receive SCThrive and participants who receive uniform standard care (SCHealthED which = standard of care plus SCD educational text messages) to see if there are differences in patient activation, self-management behaviors, daily functioning, and emergency room visits.

European Rare Blood Disorders Platform (ENROL)

ENROL, the European Rare Blood Disorders Platform has been conceived in the core of ERN-EuroBloodNet as an umbrella for both new and already existing registries on Rare Hematological Diseases (RHDs). ENROL aims at avoiding fragmentation of data by promoting the standards for patient registries' interoperability released by the EU RD platform. ENROL's principle is to maximize public benefit from data on RHDs opened up through the platform with the only restriction needed to guarantee patient rights and confidentiality, in agreement with EU regulations for cross-border sharing of personal data. Accordingly, ENROL will map the EU-level demographics, survival rates, diagnosis methods, genetic information, main clinical manifestations, and treatments in order to obtain epidemiological figures and identify trial cohorts for basic and clinical research. To this aim, ENROL will connect and facilitate the upgrading of existing RHD registries, while promoting the building of new ones when / where lacking. Target-driven actions will be carried out in collaboration with EURORDIS for educating patients and families about the benefits of enrolment in such registries, including different cultural and linguistic strategies. The standardized collection and monitoring of disease-specific healthcare outcomes through the ENROL user-friendly platform will determine how specialized care is delivered, where are the gaps in diagnosis, care, or treatment and where best to allocate financial, technical, or human resources. Moreover, it will allow for promoting research, especially for those issues that remain unanswered or sub-optimally addressed by the scientific community; furthermore, it will allow promoting clinical trials for new drugs. ENROL will enable the generation of evidence for better healthcare for RHD patients in the EU as the ultimate goal. ENROL officially started on 1st June 2020 with a duration of 36 months. ENROL is co-funded by the Health Programme of the European Union under the call for proposals HP-PJ-2019 on Rare disease registries for the European Reference Networks. GA number 947670