Observational Study to Deeply Phenotype Major Organs in Sickle Cell Disease After Curative Therapies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Change in LVEDV/BSA in patients with SCD who undergo curative therapies as compared to patients who receive non-curative treatment
研究概览
简要总结
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.
详细描述
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. Patients who undergo curative therapies will be compared to adults with SCD who receive non-curative therapies at baseline and 2 years later. The primary hypothesis is that diastolic function will improve after successful curative therapy as compared to those receiving non-curative therapies. Secondary analyses will include assessment of cardiopulmonary and kidney function. This study includes assessment of organs before and 2 years after curative and non-curative therapies with deep phenotyping of the heart, lung, liver, brain, cognitive, and kidney function. 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
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Male or female, aged >=18 years
- •Patients with current or previous diagnosis of any type of SCD (including HbSS, HbSC, HbSbeta^0-thal, HbSbeta^+-thal) who:
- •plan to receive an allogeneic HCT or gene therapy,
- •are receiving non-curative treatment (standard of care or investigational) and who do not plan to receive an allogeneic HCT or gene therapy
- •Ability to travel to the NIH Clinical Center
- •Ability of subject to understand a written informed consent document.
- •At least one of the following eligibility criteria:
- •History of stroke (including silent stroke) or abnormal transcranial doppler examination (>= 200 m/s)
- •Progression of central nervous system vasculopathy on MRA
- •History of SCD-related renal insufficiency defined as nephrotic syndrome OR creatinine clearance < 60mL/min OR a creatinine level >=1.3 mg/dL AND kidney biopsy consistent with sickle cell nephropathy
- •Tricuspid regurgitant velocity >= 2.5 m/s
- •Recurrent tricorporal priapism defined as at least 2 episodes of an erection lasting > 4 hours involving the corpora cavernosa and corpus spongiosa
- •SCD-associated liver disease defined as EITHER ferritin > 1000 mcg/L OR direct bilirubin > 0.4 mg/dL
- •> 1 hospitalization per year for vaso-occlusive crises while receiving hydroxyurea treatment
- •A history of 2 or more acute chest syndrome episodes in the participant's lifetime.
- •Avascular necrosis of 2 or more joints
- •Red cell alloimmunization (delayed hemolytic transfusion reaction or significant red blood cell alloimmunization that makes transfusion difficult).
- •Administration of regular red blood cell (RBC) transfusion therapy (>=8 red cell transfusions in the previous 12 months) to prevent SCD complications (i.e. pain, stroke, or acute chest syndrome).
- •Eligible for an allogeneic HCT or gene therapy at an outside transplant center.
排除标准
- •All individuals meeting any of the exclusion criteria at baseline will be excluded from study participation.
- •Prior transplantation (including but not limited to HSCT and kidney transplant)
- •Pregnant or breastfeeding
- •Patients with allergy to iodine or iodinated contrast solutions will not undergo Iothalamate or Iohexol GFR clearance testing but can undergo the other deep phenotype testing
- •Implanted metal object that is not compatible with MRI (e.g.: cerebral aneurysm clip, cochlear implant, or pacemaker)
- •Patients with a pacemaker or automated implantable cardioverter defibrillator will not undergo VCTE but can enroll and undergo the other deep phenotype testing as long as the device is compatible with MRI and MRI testing can be performed
- •Patients requiring peritoneal or hemodialysis
- •Uncontrolled infection or acute illness
研究组 & 干预措施
subjects w sickle cell disease
to evaluate heart, lung, liver, kidney, brain, and neurocognitive function post-hematopoietic stem cell transplant (HSCT) in subjects with sickle cell disease (SCD) who undergo curative therapies
结局指标
主要结局
Change in LVEDV/BSA in patients with SCD who undergo curative therapies as compared to patients who receive non-curative treatment
时间窗: 2 years after initial testing
Evaluate whether diastolic function improves significantly more in patients who receive curative therapies as compared to those who receive non-curative treatment.
次要结局
- Change in N-terminal pro b-type natriuretic peptide (NTproBNP).(2 years)
- Change in left ventricular end diastolic diameter (LVEDD), ejection fraction, left ventricular mass index, left atrial volume index, global longitudinal strain(2 years)
- 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(2 years)