Sickle Cell Clinical Research and Intervention Program

• ClinicalTrials.gov Identifier: NCT02098863
• Recruitment Status: Recruiting
• First Posted: March 28, 2014
• Last Update Posted: November 18, 2022
• Sponsor: St. Jude Children's Research Hospital
• Collaborators: University of Memphis School of Public Health; Le Bonheur Children's Hospital; University of Alabama at Birmingham; Washington University School of Medicine; UTHSC-ORNL Center in Biomedical Informatics; University of Washington; Medical College of Wisconsin; University of Tennessee; Children's Hospital of Philadelphia; National Heart, Lung, and Blood Institute (NHLBI); Vanderbilt University School of Medicine; Baylor College of Medicine
• Information provided by (Responsible Party): St. Jude Children's Research Hospital

Tracking Information

• First Submitted Date: March 21, 2014
• First Posted Date: March 28, 2014
• Last Update Posted Date: November 18, 2022
• Actual Study Start Date: April 15, 2014
• Estimated Primary Completion Date: December 2044 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 19, 2018)

• Relationship between treatment plan and health outcomes in participants with sickle cell disease (SCD) [ Time Frame: 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 ]
  As described in the Detailed Description, standard of care data will be collected from participants every two years during participants' annual clinic visits until study participation is discontinued or until participants reach death/end of life, whichever occurs last. This collection of observational data will be entered into a study database and will serve as a research resource to facilitate evaluation of health outcomes in participants with SCD from pediatric care into adulthood.
• Relationship between genetic properties of biological samples and health outcomes in participants with sickle cell disease [ Time Frame: Collected every 6 years from newborn until end-of life, up until December 2044 ]
  A repository of biological samples from participants with sickle cell disease will be established for future retrospective studies investigating genetic and epigenetic contributions to disease severity, response to treatment, and morbidity and mortality.

Original Primary Outcome Measures (submitted: March 25, 2014)

• Relationship between treatment plan and health outcomes in participants with sickle cell disease (SCD) [ Time Frame: From newborn to ≤ 25 years of age ]
  As described in the Detailed Description, standard of care data will be collected from participants every two years during participants' annual clinic visits until study participation is discontinued or until participants reach 25 years of age, whichever occurs last. This collection of observational data will be entered into a study database and will serve as a research resource to facilitate evaluation of health outcomes in participants with SCD from pediatric care into adulthood.
• Relationship between genetic properties of biological samples and health outcomes in participants with sickle cell disease [ Time Frame: Collected at newborn and ages 6, 12, 18 and 24 ]
  A repository of biological samples from participants with sickle cell disease will be established for future retrospective studies investigating genetic and epigenetic contributions to disease severity, response to treatment, and morbidity and mortality.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sickle Cell Clinical Research and Intervention Program
• Official Title: Sickle Cell Clinical Research and Intervention Program

Brief Summary

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.

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.

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. Two 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: Peoria, Illinois and Charlotte, North Carolina. Approximately 300 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.

• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: 99 Years

Biospecimen

Retention:   Samples With DNA

Description:

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 in St. Jude Biorepository. In addition, buccal, nasal, and rectal swabs and stool samples will be collected from participants and stored in the Infectious Disease repository 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.

• Sampling Method: Non-Probability Sample
• Study Population: Participants with a diagnosis of sickle cell disease of any genotype.
• Condition: Sickle Cell Disease
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Champlin G, Hwang SN, Heitzer A, Ding J, Jacola L, Estepp JH, Wang W, Ataga KI, Owens CL, Newman J, King AA, Davis R, Kang G, Hankins JS. Progression of central nervous system disease from pediatric to young adulthood in sickle cell anemia. Exp Biol Med (Maywood). 2021 Dec;246(23):2473-2479. doi: 10.1177/15353702211035778. Epub 2021 Aug 18.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 5, 2019): 10000
• Original Estimated Enrollment (submitted: March 25, 2014): 1000
• Estimated Study Completion Date: December 2044
• Estimated Primary Completion Date: December 2044 (Final data collection date for primary outcome measure)

Eligibility 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, 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: Jane Hankins, MD, MS; 866-278-5833; referralinfo@stjude.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02098863
• Other Study ID Numbers: SCCRIP; 1U01HL133996 ( U.S. NIH Grant/Contract ); UTHSC-MRC Sub ( Other Grant/Funding Number: Tennessee State )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: St. Jude Children's Research Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: St. Jude Children's Research Hospital
• Original Study Sponsor: Same as current

Collaborators

• University of Memphis School of Public Health
• Le Bonheur Children's Hospital
• University of Alabama at Birmingham
• Washington University School of Medicine
• UTHSC-ORNL Center in Biomedical Informatics
• University of Washington
• Medical College of Wisconsin
• University of Tennessee
• Children's Hospital of Philadelphia
• National Heart, Lung, and Blood Institute (NHLBI)
• Vanderbilt University School of Medicine
• Baylor College of Medicine

Investigators

• Principal Investigator: Jane Hankins, MD, MS; St. Jude Children's Research Hospital

• PRS Account: St. Jude Children's Research Hospital
• Verification Date: November 2022