Mortality in Sickle CellNCT05213572
Observational Study to Deeply Phenotype Major Organs in Sickle Cell Disease After Curative Therapies
An observational study of Mortality in Sickle Cell and Sickle Cell Cardiopulmonary Complications, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Mortality in Sickle Cell, Sickle Cell Cardiopulmonary Complications, Sickle Cell Organ Damage
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Mar 2022to 1 Jun 2035
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients aged >or= 18 years who will undergo curative therapies at the NIH Clinical Center and who have a diagnosis of any type of SCD (including HbSS, HbSC, HbSbeta0-thal, HbSbeta+-thal).
Who may be able to join
- 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,
- Or
Show all 22Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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.
Read more
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.
Read the detailed description
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
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.
- Evaluate regional oxygenation (rS0(2)) 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-gamma) and tumor necrosis factor alpha (TNF-a), chemokines, GlycA, D-dimer, 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 rS0(2) 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.
- Conditions
- Mortality in Sickle Cell, Sickle Cell Cardiopulmonary Complications, Sickle Cell Organ Damage, Sickle Cell Life Expectancy and Risk Factors for Early Death, Sickle Cell Lung Disease and Sudden Death
- Keywords
- Hydroxyurea, Hydroxyurea-Increased Fetal Hemoglobin, sickle cell anemi, Patterns of mortality in sickle cell disease, Mortality rates and age at death from sickle cell, Natural History
- Medical subject headings
- Death, Sudden
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in LVEDV/BSA in patients with SCD who undergo curative therapies as compared to patients who receive non-curative treatment
Evaluate whether diastolic function improves significantly more in patients who receive curative therapies as compared to those who receive non-curative treatment.
Measured: 2 years after initial testing
Secondary outcomes (3)
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
Evaluate change in kidney function over time in patients with SCD who undergo curative therapies as compared to those who receive non-curative treatment.
Measured: 2 years
Change in N-terminal pro b-type natriuretic peptide (NTproBNP).
Evaluate whether cardiopulmonary function improves more in patients who receive curative therapies as compared to non-curative therapy.
Measured: 2 years
Change in left ventricular end diastolic diameter (LVEDD), ejection fraction, left ventricular mass index, left atrial volume index, global longitudinal strain
Evaluate whether cardiopulmonary function improves more in patients who receive curative therapies as compared to non-curative therapy.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2022
- Study start24 Mar 2022
- Primary completion1 Jun 2035 (estimated)
- Study completion1 Jun 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mortality in Sickle CellStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Courtney F Joseph, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05213572
- Sponsor's protocol ID
- 10000479
- Other IDs
- 000479-H
- Status last verified
- 16 Oct 2026
- First submitted
- 27 Jan 2022
- Last updated
- 22 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study to Deeply Phenotype Major Organs in Sickle Cell Disease After Curative Therapies
- ClinicalTrials.gov ID
- NCT05213572
- Acronym / sponsor ID
- 10000479
- Conditions
- Mortality in Sickle Cell, Sickle Cell Cardiopulmonary Complications, Sickle Cell Organ Damage, Sickle Cell Life Expectancy and Risk Factors for Early Death, Sickle Cell Lung Disease and Sudden Death
- Keywords
- Hydroxyurea, Hydroxyurea-Increased Fetal Hemoglobin, sickle cell anemi, Patterns of mortality in sickle cell disease, Mortality rates and age at death from sickle cell, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 24 Mar 2022 (actual)
- Primary completion
- 1 Jun 2035 (estimated)
- Study completion
- 1 Jun 2035 (estimated)
- First posted
- 28 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
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.
- Evaluate regional oxygenation (rS0(2)) 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-gamma) and tumor necrosis factor alpha (TNF-a), chemokines, GlycA, D-dimer, 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 rS0(2) 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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients aged >or= 18 years who will undergo curative therapies at the NIH Clinical Center and who have a diagnosis of any type of SCD (including HbSS, HbSC, HbSbeta0-thal, HbSbeta+-thal).
Key inclusion criteria (22 listed)
- 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:
- Or
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in LVEDV/BSA in patients with SCD who undergo curative therapies as compared to patients who receive non-curative treatment
Time frame: 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.
3 secondary outcomes
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
Time frame: 2 years
Change in N-terminal pro b-type natriuretic peptide (NTproBNP).
Time frame: 2 years
Change in left ventricular end diastolic diameter (LVEDD), ejection fraction, left ventricular mass index, left atrial volume index, global longitudinal strain
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Courtney F Joseph, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mortality in Sickle Cell and Sickle Cell Cardiopulmonary Complications, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julia M Varga, R.N. ((301) 402-3595, julia.varga@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in LVEDV/BSA in patients with SCD who undergo curative therapies as compared to patients who receive non-curative treatment (time frame: 2 years after initial testing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.