Sickle Cell Clinical Research and Intervention Program
Sickle Cell Clinical Research and Intervention Program
Despite the important work of previous sickle cell disease (SCD) cohort studies, there remain
 many understudied areas that require investigation. An important knowledge deficit is the
 slow but progressive process of chronic end-organ dysfunction. The majority of organ
 dysfunction becomes apparent in the young adult years, but comprehensive assessment of adults
 and understanding of predictors of adulthood organ dysfunction are insufficient. Similarly,
 the role of disease-modifying therapies, such as hydroxyurea, in preventing organ dysfunction
 later in life is not clear. Extended follow-up of patients through the transition into
 adulthood is imperative to understand the long-term implications of pediatric sickle cell
 care.

 This observational study will collect data in a systematic fashion at participants' regular
 clinic visits (in-person or remote) to answer the objectives described below.

 In addition to primary study objectives, SCCRIP participants will be eligible to participate
 in a sub-study, which will investigate genetically determined responses to Hydroxyurea (HU)
 via a pharmacokinetic study (PK). This one time study will involve blood collection at timed
 intervals proceeding a dose of HU. Defining the basis for this inter-individual variability
 will allow the identification of poor HU responders prior to initiation of therapy and the
 seeking of alternative treatments which seek to optimize disease treatment by accounting for
 individual variability in genes, environment, and lifestyle.
The St. Jude Pediatric SCD Program has developed a comprehensive plan of care that spans the
 ages of 0 to 25, and provides the structure for screening and monitoring disease progression
 and complications in infancy, childhood, and young adulthood. From age 0 to 18, SCD patients
 are followed at St. Jude Children's Research Hospital. At age 18, their care is typically
 transferred to either the Methodist Adult Comprehensive Sickle Cell Disease Center in
 Memphis, TN, or the Regional One Health, Diggs-Kraus Sickle Cell Center in Memphis, TN, where
 they are routinely followed from age 18 to 25 years. After age 25, participants will be
 followed and invited to return to St. Jude every 6 years for study related tests until
 participants elect to come off study or until death.

 St. Jude Children's Research Hospital, the Methodist Adult Comprehensive Sickle Cell Disease
 Center and the Regional One Health Diggs-Kraus Sickle Cell Center, in Memphis, TN serve as
 enrolling centers for the SCCRIP protocol.Three St. Jude Affiliate locations will also be
 sites of enrollment for this protocol for patients age 0 to 18 years. These include St. Jude
 Affiliate sites located in: Baton Rouge, Louisiana; Peoria, Illinois; and Charlotte, North
 Carolina. Approximately 500 additional participants are expected to be enrolled from these
 affiliate sites. This protocol will collect data on SCD participants from birth to end of
 life.

 The SCD plan of care provides the specific sequence of laboratory and imaging studies that
 are performed according to the patient's age and expected course of illness. The following
 health outcomes are systematically monitored in patients with SCD: hematologic indices,
 pulmonary function, cardiac function, renal function, cognitive function, cerebral
 vasculopathy, vitamin D deficiency and bone health, parvovirus B19 immune status,
 ophthalmologic status, and splenic function. These tests are used to direct the patient's
 clinical management and initiate therapies when necessary.

 Participants who reach 20 (± approximately 1 year) years of age and are enrolled on SCCRIP
 Amendment 6.0 or above, may participate in a neuropsychological screening. The screening will
 include a series of verbal and nonverbal problem-solving activities, pencil & paper tasks,
 and will include a computerized component.

 Quality of Life evaluations (Pediatric Quality of Life Inventory (PedsQL™) will be offered.

 In this study, the results of these tests will be collected and entered into the study
 database, providing longitudinal data that will inform health outcomes research regarding SCD
 and how the course is altered by disease-modifying therapy, in addition to facilitating
 future interventional projects.

 Primary Objectives:

 -  To establish a longitudinal clinical cohort of patients with sickle cell disease (SCD)
 to serve as a research resource to facilitate evaluation of health outcomes in SCD from
 pediatric care into adulthood.

 -  To facilitate the collection of biological samples from patients with SCD to be used in
 future studies investigating genetic and epigenetic contributions to disease severity,
 response to treatment, and morbidity and mortality.

 Secondary Objectives:

 -  To determine the incidence, prevalence, and severity of SCD complications and adverse
 health conditions within the SCD cohort during five stages of development and adulthood:
 the newborn period (birth to 5.9 months), the infant/pre-school stage (ages 6 months to
 5.9 years), the early school stage (ages 6 to 11.9 years), the adolescent stage (ages 12
 to 17.9 years), young adulthood (ages 18 to 24.9 years) and mature adulthood (ages 25
 and above).

 -  To identify and evaluate risk factors for premature mortality and long-term morbidity in
 patients with SCD, including those related to disease-modifying therapies, end-organ
 damage, genetics, neurocognitive deficits, psychosocial factors, and behavioral causes.

 -  To investigate the long-term effects of hydroxyurea and other therapies on preservation
 of organ function, growth and development, and frequency and severity of disease
 complications, and their long-term medical, neurocognitive, and psychosocial toxicities.

 -  To determine the functional aspects of the Transition to Adult Care Program within a
 clinical research cohort by evaluating disease specific health literacy and readiness in
 relation to healthcare utilization during adult care.

 -  To explore the long-term alterations of prolonged antibiotic exposure on the microbial
 community composition among people living with SCD through the collection of swabs as
 guided by the Human Microbiome Project (HMP) Manual of Procedures.

 Other Pre-Specified Objective:

 -  Define the drug-exposure to clinical response relationship of HU therapy in children
 with SCD.
SCCRIP Inclusion Criteria:

 -  A diagnosis of sickle cell disease of any genotype.

 -  PK Sub-study Inclusion Criteria:

 -  Participants at St. Jude Children's Research Hospital who are consented to the
 parent protocol (SCCRIP, Amendment 6.1 or above).

 -  Participants currently completing a hydroxyurea (HU) regimen, who have achieved
 maximum tolerated dose and have maintained that dose for a minimum of 90 days
 prior to enrollment.

 SCCRIP Exclusion Criteria:

 -  Any medical or social reason, which, in the opinion of the principal investigators
 would make the participation of the subject ill-advised.

 -  PK Sub-study Exclusion Criteria:

 -  Participants unable to complete the blood draws required for PK sampling.

 -  Inability or unwillingness of research participant or legal
 guardian/representative to give written informed consent.

 -  Any medical or social reason, which, in the opinion of the principal
 investigators would make the participation of the subject ill-advised.