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.
To study the benefits of treatments that are intended to cure SCD.
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.
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.
|Jennifer L Brooks, R.N.|
|Courtney D Fitzhugh, M.D.|
> 18 Years
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
Current or previous diagnosis of any type of SCD (including HbSS, HbSC, HbSbeta0-thal, HbSbeta+-thal)
Ability to travel to the NIH Clinical Center
Ability of subject to understand and the willingness to sign a written informed consent document.
Ability to undergo required studies except as specified in the
Curative Therapies Group
–Plan to receive conditioning for curative therapy at the NIH Clinical Center, Vanderbilt University Medical Center, or Johns Hopkins Hospital
Non-Curative Therapy Group
— No plan to undergo curative therapy within 2 years
At least one of the following eligibility criteria:
History of stroke or abnormal transcranial doppler examination (>= 200 m/s)
History of SCD-related renal insufficiency defined as a creatinine level >=1.3 mg/dL and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance < 50mL/min 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 on a therapeutic dose of hydroxyurea
Any acute chest syndrome while on a therapeutic dose of hydroxyurea
Osteonecrosis of 2 or more joints
Red cell alloimmunization
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 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
Criteria specific to the non-curative therapy group:
Hydroxyurea initiation or dose adjustment <2 months prior Initiation of chronic transfusion therapy <2 months prior Antihypertensive medication initiation or dose adjustment <1 month prior