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

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ClinicalTrials.gov Identifier: NCT05213572
Recruitment Status : Recruiting
First Posted : January 28, 2022
Last Update Posted : January 25, 2023
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Study Description
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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.


Condition or disease
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

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Study Design
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Study Type : Observational
Estimated Enrollment : 180 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Observational Study to Deeply Phenotype Major Organs in Sickle Cell Disease After Curative Therapies
Actual Study Start Date : March 24, 2022
Estimated Primary Completion Date : June 1, 2035
Estimated Study Completion Date : June 1, 2035

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort
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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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 ]
    Evaluate change in kidney function over time in patients with SCD who undergo curative therapies as compared to those who receive non-curative treatment.

  2. Change in N-terminal pro b-type natriuretic peptide (NTproBNP). [ Time Frame: 2 years ]
    Evaluate whether cardiopulmonary function improves more in patients who receive curative therapies as compared to non-curative therapy.

  3. 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 ]
    Evaluate whether cardiopulmonary function improves more in patients who receive curative therapies as compared to non-curative therapy.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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).
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. Current or previous diagnosis of any type of SCD (including HbSS, HbSC, HbSbeta0-thal, HbSbeta+-thal)
  4. Ability to travel to the NIH Clinical Center
  5. Ability of subject to understand and the willingness to sign a written informed consent document.
  6. Ability to undergo required studies except as specified in the Exclusion Criteria.

  7. Curative Therapies Group

    --Plan to receive conditioning for curative therapy at the NIH Clinical Center, Vanderbilt University Medical Center, or Johns Hopkins Hospital

  8. Non-Curative Therapy Group

    -- No plan to undergo curative therapy within 2 years

  9. 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 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

  8. Criteria specific to the non-curative therapy group:

    1. Hydroxyurea initiation or dose adjustment <2 months prior
    2. Initiation of chronic transfusion therapy <2 months prior
    3. Antihypertensive medication initiation or dose adjustment <1 month prior
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05213572


Contacts
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Contact: Jennifer L Brooks, R.N. (301) 480-6149 jennifer.brooks2@nih.gov
Contact: Courtney D Fitzhugh, M.D. (301) 402-6496 courtney.fitzhugh@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY dial 711    ccopr@nih.gov   
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Courtney D Fitzhugh, M.D. National Heart, Lung, and Blood Institute (NHLBI)
More Information
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

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Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT05213572    
Other Study ID Numbers: 10000479
000479-H
First Posted: January 28, 2022    Key Record Dates
Last Update Posted: January 25, 2023
Last Verified: January 22, 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
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
Additional relevant MeSH terms:
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Lung Diseases
Anemia, Sickle Cell
Death
Death, Sudden
Respiratory Tract Diseases
Pathologic Processes
 Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn