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 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.

Detailed Description

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. 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. 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 6 months), the infant/pre-school stage (ages 6 months to 6 years), the early school stage (ages 6 to 12 years), the adolescent stage (ages 12 to 18 years), the years of transition into young adulthood (ages 18 to 25 years), and adulthood (ages 26 years 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. Other Pre-Specified Objective: - Define the drug-exposure to clinical response relationship of HU therapy in children with SCD.

Overall Status

Recruiting

Start Date

2014-04-15

Completion Date

2044-12-01

Primary Completion Date

2044-12-01

Study Type

Observational [Patient Registry]

Primary Outcome

Measure	Time Frame
Relationship between treatment plan and health outcomes in participants with sickle cell disease (SCD)	Every 2 years from newborn to ≤ 30 years of age, and every 6 years after age 30 until end-of-life, up until December 2044
Relationship between genetic properties of biological samples and health outcomes in participants with sickle cell disease	Collected every 6 years from newborn until end-of life, up until December 2044

Enrollment

1550

Condition

Sickle Cell Disease

Eligibility

Study Pop

Participants with a diagnosis of sickle cell disease of any genotype.

Sampling Method

Non-Probability Sample

Criteria

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). - 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.

Gender

All

Minimum Age

N/A

Maximum Age

N/A

Healthy Volunteers

Overall Official

Last Name	Role	Affiliation
Jane Hankins, MD, MS	Principal Investigator	St. Jude Children's Research Hospital

Overall Contact

Last Name

Jane Hankins, MD, MS

Phone

866-278-5833

Email

[email protected]

Location

Facility	Status	Contact	Investigator
Children's Hospital of Illinois at OSF-Saint Francis Medical Center Peoria Illinois 61637 United States	Recruiting	Last Name: Kay Saving, MD Phone: 309-624-4945	Last Name: Kay Saving, MD Role: Principal Investigator
Our Lady of the Lake Regional Medical Center Baton Rouge Louisiana 70808 United States	Recruiting	Last Name: Jeff Deyo, MD, PhD Phone: 225-763-6337	Last Name: Jeff Deyo, MD, PhD Role: Principal Investigator
Novant Health Hemby Children's Hospital Charlotte North Carolina 28204 United States	Recruiting	Last Name: Paulette Bryant, MD Phone: 704-384-1900	Last Name: Paulette Bryant, MD Role: Principal Investigator
Regional One Health, Diggs-Kraus Sickle Cell Center Memphis Tennessee 38103 United States	Not yet recruiting	Last Name: Patricia Adams-Graves, MD Phone: 901-545-8535	Last Name: Patricia Adams-Graves, MD Role: Principal Investigator
Methodist Adult Comprehensive Sickle Cell Center Memphis Tennessee 38104 United States	Recruiting	Last Name: Curtis Owens, MD Phone: 901-516-8182	Last Name: Curtis Owens, MD Role: Principal Investigator
St. Jude Children's Research Hospital Memphis Tennessee 38105 United States	Recruiting	Last Name: Jane Hankins, MD, MS Phone: 866-278-5833 Email: [email protected]	Last Name: Jane Hankins, MD, MS Role: Principal Investigator

Location Countries

Country

United States

Verification Date

2018-08-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Sponsor

Keywords

Sickle Cell Anemia

, Sickle Cell Disease

, Survival

, Mortality

, End-Order Dysfunction

Has Expanded Access

Condition Browse

Anemia, Sickle Cell

Secondary Id

1U01HL133996

UTHSC-MRC Sub

Firstreceived Results Date

N/A

Biospec Retention

Samples With DNA

Biospec Descr

All participants will be offered the option of having biological specimens collected and saved for future research. DNA, plasma, and urine will be collected from participants and stored at Tissue Resources at St. Jude Children's Research Hospital. This will facilitate future high quality genotype-phenotype studies and other genetic and proteomic studies related to variability in disease severity, treatment response, and health outcomes.

Target Duration

30 Years

Firstreceived Results Disposition Date

N/A

Study Design Info

Observational Model

Cohort

Time Perspective

Prospective

Study First Submitted

March 21, 2014

Study First Submitted Qc

March 25, 2014

Study First Posted

March 28, 2014

Last Update Submitted

August 23, 2018

Last Update Submitted Qc

August 23, 2018

Last Update Posted

August 27, 2018

ClinicalTrials.gov processed this data on September 27, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.

Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.

Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.

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