Evaluating organ health in sickle cell disease after curative treatments

Observational Study to Deeply Phenotype Major Organs in Sickle Cell Disease After Curative Therapies

This study is trying to see how curative treatments for sickle cell disease affect the health of major organs in adults over two years.

Quick facts

• Study type: Observational
• Enrollment: 200 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05213572 on ClinicalTrials.gov

What this trial studies

This observational study aims to deeply phenotype major organs in patients with sickle cell disease (SCD) who are undergoing or have undergone curative therapies. Participants aged 18 and older will be assessed for heart, lung, liver, kidney, brain, and cognitive function before and two years after treatment. The study will compare outcomes between those receiving curative therapies and those on non-curative therapies, utilizing various tests including blood work, MRI scans, and cognitive assessments. The goal is to understand the impact of curative therapies on organ function and overall health in SCD patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of sickle cell disease who are planning to receive curative therapy or have no plans for such therapy in the next two years.

Not a fit: Patients who do not have sickle cell disease or those who are not able to comply with study procedures may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of organ health in sickle cell disease, potentially enhancing life expectancy and quality of life for patients.

How similar studies have performed: While this study employs a novel approach to evaluate organ function post-curative therapy, similar studies have shown promising results in understanding the impacts of treatments on sickle cell disease.

Eligibility criteria

* 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, HbSbeta0-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 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

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 Iohexal 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

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Courtney F Joseph, M.D. — National Heart, Lung, and Blood Institute (NHLBI)
• Study coordinator: Julia M Varga, R.N.

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; Hydroxyurea; Hydroxyurea-Increased Fetal Hemoglobin; sickle cell anemi