Mortality in Sickle Cell Clinical Trial
Official title:
Observational Study to Deeply Phenotype Major Organs in Sickle Cell Disease After Curative Therapies
Background: People with sickle cell disease (SCD) have problems with their heart, brain, kidneys, liver, and lungs as they age. These problems may improve after transplant. Researchers want to learn how and why this happens. Objective: To study the benefits of treatments that are intended to cure SCD. Eligibility: People aged 18 and older with SCD who are either receiving curative therapy in the next 3 months or don t have any plans to receive a curative therapy in the next 2 years. Design: At their first visit, participants will be screened with their medical history and a physical exam. Participants will then have a baseline visit. This will take about a week to complete and will include: Blood and heart tests MRI of the brain, heart, and lungs. Participants will lie on a bed that will move into the MRI scanner. Special padding may be placed around their head to keep it still. Interactive games. Participants will complete computer games that test memory, attention, problem solving, language, spatial orientation, processing speed, and emotion. Questionnaire rating quality of life Iothalamate test. An IV catheter will be placed into a vein. A contrast agent will be injected through the IV. Blood will then be collected at different time points. Lung function tests and a 6-minute walk test Vibration controlled transient elastography. A probe placed on the abdomen will measure liver scarring. DOS test. A light attached to the finger or toe will measure blood oxygen. Participants will have an end-of-study visit about 2 years after their baseline visit. This will include repeats of the baseline visit tests.
Study Description: This study seeks to evaluate heart, lung, liver, kidney, brain, and neurocognitive function post-hematopoietic stem cell transplant (HSCT) in patients with sickle cell disease (SCD) who undergo curative therapies. Based on our preliminary data, the primary hypothesis is that diastolic function will improve after successful curative therapy as compared to baseline. Secondary analyses will include assessment of cardiopulmonary and kidney function. This study includes assessment of organs before and 2 years after curative therapies with deep phenotyping of the heart, lung, liver, brain, cognitive, and kidney function. Patients who undergo curative therapies will be compared to adults with SCD who receive non-curative therapies at baseline and 2 years later. This protocol will allow us to comprehensively explore sequelae of curative therapies on organ function in patients with SCD. Objectives: Primary Objective: -Evaluate left ventricular end diastolic volume/body surface area (LVEDV/BSA) in patients with SCD who undergo curative therapies as compared to patients who receive non-curative therapies at 2 years after initial testing. Secondary Objectives: - Evaluate other markers of cardiopulmonary function in patients with SCD who undergo curative therapies as compared to those who receive non-curative therapies. - Evaluate change in kidney function over time in patients with SCD who undergo curative therapies as compared to those who receive non-curative therapies. Tertiary Objectives: - Perform deep phenotyping of heart, lung, liver, kidney, brain and neurocognitive function along with reported genetic variants in adults with SCD who undergo curative therapies as compared to adults with SCD who receive non-curative therapies. - Assess markers of inflammation in patients with SCD who undergo curative therapies as compared to those who receive non-curative therapies. - Evaluate markers of graft rejection and tolerance induction in patients with SCD who undergo curative therapies. - Evaluate lipid profiles in patients with SCD who undergo curative therapies as compared to those who receive non-curative therapies. - Assess whether curative therapies modulate sickle cell-associated coagulopathy as compared to those who receive non-curative therapies. - Evaluate regional oxygenation (rS02) with Near Infrared Spectroscopy (NIRS) in patients with SCD who undergo curative therapies as compared to those who receive non-curative therapies. - Evaluate novel biomarkers of organ damage in patients who receive curative therapies as compared to those who receive non-curative therapies. Endpoints: Primary Endpoint: - Change in LVEDV/BSA Secondary Endpoints: - Change in left ventricular end diastolic diameter (LVEDD), ejection fraction, left ventricular mass index, left atrial volume index, global longitudinal strain - Change in N-terminal pro b-type natriuretic peptide (NTproBNP). - Change in creatinine, cystatin-C, urine protein to creatinine ratio, urine albumin to creatinine ratio, and estimated glomerular filtration rate (eGFR) using the CKD-EPI equation Tertiary Endpoints: - Change in myocardial fibrosis, extracellular volume fraction, processing speed, measured GFR, incidence of stroke/silent infarcts, cerebral blood flow, oxygen extraction fraction, and liver stiffness, and correlation of APOL1 risk alleles with renal function and degree of proteinuria - Change in c-reactive protein (CRP), erythrocyte sedimentation rate (ESR), inflammatory cytokines (including interferon gamma (IFN-y) and tumor necrosis factor alpha (TNF-a), chemokines, GlycA, and haptoglobin - Change in regulatory cells (including regulatory T cells and myeloid-derived suppressor cells) and proteins (including galectin, platelet factor 4, and thrombospondin-1) and suppressive cytokines (interleukin-10 (IL-10), transforming growth factor beta, and IL-7) - Change in very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle size and number, triglycerides, and apolipoprotein A-I and B - Change in Thrombin anti-thrombin complexes, D-dimer, prothrombin fragment 1.2 monocyte cell surface expression of tissue factor (TF), monocyte and endothelial cell-derived TF+ extracellular vesicles (EVs), procoagulant activity of TF+ EVs and proadhesive biomarkers including red blood cell surface phosphatidylserine exposure and circulating heterocellular aggregates - Change in rS02 within the peripheral limb with NIRS - Correlation of novel genetic biomarkers associated with organ damage in patients with SCD who receive curative therapy or noncurative therapy. ;