Recruiting

Observational Study

Sponsor:

National Heart, Lung, and Blood Institute (NHLBI)

Code:

NCT05213572

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

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Study Details

Brief 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.

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.

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

Study ID

NCT05213572

Start date

Mar 24, 2022

Status verified date

Aug 20, 2026

Completion date

Jun 1, 2035

Anticipated

Primary completion date

Jun 1, 2035

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

  • INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Stated willingness to comply with all study procedures and availability for the duration of the study
2. Male or female, aged >=18 years
3. Patients with current or previous diagnosis of any type of SCD (including HbSS, HbSC, HbSbeta\^0-thal, HbSbeta\^+-thal) who:

1. plan to receive an allogeneic HCT or gene therapy,

Or
2. are receiving non-curative treatment (standard of care or investigational) and who do not plan to receive an allogeneic HCT or gene therapy
4. Ability to travel to the NIH Clinical Center
5. Ability of subject to understand a written informed consent document.
6. 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.

EXCLUSION CRITERIA:

All individuals meeting any of the exclusion criteria at baseline will be excluded from study participation.

1. Prior transplantation (including but not limited to HSCT and kidney transplant)
2. Pregnant or breastfeeding
3. 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
4. Implanted metal object that is not compatible with MRI (e.g.: cerebral aneurysm clip, cochlear implant, or pacemaker)
5. 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
6. Patients requiring peritoneal or hemodialysis
7. Uncontrolled infection or acute illness

Study Design

Enrollment

200 participants

Anticipated

Interventions and Outcome Measures

Arms

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

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 ]

Central Contacts and Locations

Central contacts

Julia M Varga, R.N.

(301) 402-3595julia.varga@nih.gov

Courtney F Joseph, M.D.

(301) 402-6496courtney.fitzhugh@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

800-411-1222ccopr@nih.gov

More Information

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Last update posted

Aug 27, 2026

Last verified

Aug 20, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Heart, Lung, and Blood Institute (NHLBI) on 2026-08-27.