Cooperative Assessment of Late Effects for SCD Curative Therapies

NCT05153967 | Recruiting

• 1 other identifier: 210806
• Study Type: observational
• Target: 750
• Locations: 1 country
• Sites: 5

Brief Summary

Sickle Cell Disease is one of the most common genetic diseases in the United States, occurring in approximately 1 in 400 births. Approximately 100,000 individuals are diagnosed with SCD in the United States. Mortality for children with SCD has decreased substantially over the past 4 decades, with \>99% of those born in high resource settings, including the United States, France, and England, now surviving to 18 years of age. However, the life expectancy of adults with SCD is severely shortened. Dysfunction of the heart, lung, and kidney is directly associated with decreased life expectancy. With the variety of curative therapies that are now available for SCD, long-term health outcomes studies are time-sensitive. As of now, efforts to determine long-term health outcomes following curative therapies for SCD have been limited. Though curative therapies initially should provide a cure for symptoms of SCD, there is the risk of late health outcomes to consider. Defining health outcomes following curative therapy is essential to improve personalized decision-making when considering curative versus disease-modifying therapeutic options. The primary goal of this study is to determine whether curative therapies for individuals with SCD will result in improved or worsening heart, lung, and kidney damage when compared to individuals with SCD receiving standard therapy. The investigators will also explore whether certain genes are associated with a good or bad outcome after curative therapy for SCD.

Conditions

Sickle Cell Disease; Pulmonary Disease; Renal Disease; Heart Disease

Keywords

Myeloablative Autologous Gene Editing; Myeloablative Autologous Gene Therapy; Myeloablative allo-HSCT; Nonmyeloablative allo-HSCT; Disease-Modifying Therapy

Outcome Measures

Primary Outcomes (9)

• Measurement of longitudinal change in FEV1

  Measurements of forced expiratory volume in 1 second (FEV1) based on the global lung index will be acquired from children with SCD receiving myeloablative curative therapies and adults with SCD receiving nonmyeloablative allo-HSCT, as well as from the respective control children and adult cohorts with SCD who received standard therapy. FEV1 will be reported in liters. (References: Eur Respir J. Volume 40 Issue 6: pages 1324-1343, 2012 June 27; Am J Hematol. Volume 93 Issue 3: pages 408-415, 2018 March).

  Through study completion, an average of four years

• Percent predicted value of longitudinal change in FEV1

  Percent predicted of forced expiratory volume in 1 second (FEV1) based on the global lung index will be acquired from children with SCD receiving myeloablative curative therapies and adults with SCD receiving nonmyeloablative allo-HSCT, as well as from the respective control children and adult cohorts with SCD who received standard therapy. FEV1 will be reported in percentage. (References: Eur Respir J. Volume 40 Issue 6: pages 1324-1343, 2012 June 27; Am J Hematol. Volume 93 Issue 3: pages 408-415, 2018 March).

  Through study completion, an average of four years

• Measurement of longitudinal change in FVC

  Measurements of forced volume capacity (FVC) based on the global lung index will be acquired from children with SCD receiving myeloablative curative therapies and adults with SCD receiving nonmyeloablative allo-HSCT, as well as from the respective control children and adult cohorts with SCD who received standard therapy. FVC will be reported in liters. (References: Eur Respir J. Volume 40 Issue 6: pages 1324-1343, 2012 June 27; Am J Hematol. Volume 93 Issue 3: pages 408-415, 2018 March).

  Through study completion, an average of four years

• Percent predicted value of longitudinal change in FVC

  Percent predicted of forced volume capacity (FVC) on the global lung index will be acquired from children with SCD receiving myeloablative curative therapies and adults with SCD receiving nonmyeloablative allo-HSCT, as well as from the respective control children and adult cohorts with SCD who received standard therapy. FVC will be reported in percentage. (References: Eur Respir J. Volume 40 Issue 6: pages 1324-1343, 2012 June 27; Am J Hematol. Volume 93 Issue 3: pages 408-415, 2018 March).

  Through study completion, an average of four years

• FEV1/FVC Ratio Percentage

  Percentage of FEV1/FVC ratio based on the global lung index will be acquired from children with SCD receiving myeloablative curative therapies and adults with SCD receiving nonmyeloablative allo-HSCT, as well as from the respective control children and adult cohorts with SCD who received standard therapy. (References: Eur Respir J. Volume 40 Issue 6: pages 1324-1343, 2012 June 27; Am J Hematol. Volume 93 Issue 3: pages 408-415, 2018 March). FEV1/FVC will be reported in percentage.

  Through study completion, an average of four years

• Longitudinal change in eGFR

  Estimated GFR (eGFR) as a determinant of kidney disease will be collected from children with SCD receiving myeloablative curative therapies and adults with SCD receiving nonmyeloablative allo-HSCT, as well as from the respective control children and adult cohorts with SCD who received standard therapy. The eGFR will be tested as a linear variable and using eGFR Categories according to the KDIGO 2012 Guidelines (Table 5 - Reference: Kidney Int Suppl. Volume 3 Issue 1: pages 19-62, 2013 Jan) as follows: i.G1 \>/ 90 mL/min/1.73m2 ii.G2 60 - 89 mL/min/1.73m2 iii.G3a 45 - 59 mL/min/1.73m2 iv.G3b 30 - 44 mL/min/1.73m2 v.G4 15 - 20 mL/min/1.73m2 vi.G5 \< 15 mL/min/1.73m2 The standard technique of measured GFR will be used and reported in mL/min/1.73m2.

  Through study completion, an average of four years

• Longitudinal change in albuminuria levels

  Data pertaining to persistent albuminuria (defined as \>/ 30 mg/g creatinine on 2 evaluations) associated with a more rapid decline in eGFR on longitudinal follow-up (Reference: Blood Adv. Volume 4 Issue 7: pages 1501-1511, 2020 Apr 14) will be tested. Results will be reported in mg/g.

  Through study completion, an average of four years

• Longitudinal change in TRJV in adults with SCD treated with nonmyeloablative allo HSCT in adults

  Improvement in TRJV in adults with SCD following HSCT will be acquired. Results will be reported in m/sec.

  Through study completion, an average of four years

• Longitudinal change in SBP/DBP in adults with SCD treated with nonmyeloablative allo HSCT in adults

  Measurements of Systolic blood pressure (SBP)/Diastolic blood pressure (DBP) in adults with SCD following HSCT will be acquired. Results will be reported as a ratio (SBP (mmHg)/DBP (mmHg)).

  Through study completion, an average of four years

Study Arms (4)

Pediatric Myeloablative allo-HSCT

Participants ages 4 to 17 years old with SCD who underwent or are scheduled to undergo myeloablative allo-HSCT.

Pediatric Standard Disease-Modifying Therapy

Participants ages 4 to 17 years old with SCD who receive standard therapy.

Adult Non-Myeloablative allo-HSCT

Participants ages 18 to 65 years old with SCD who underwent or are scheduled to undergo non-myeloablative allo-HSCT.

Adult Standard Disease-Modifying Therapy

Participants ages 18 to 65 years old with SCD who receive standard therapy.

Eligibility Criteria

• Age: 4 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be patient volunteers from the sickle cell disease clinics and transplant centers of participating study sites.

You may qualify if:

• Confirmed laboratory diagnosis of SCD
• Ability to give informed consent
• Ability to provide pre- and post-curative therapy data
• Treated with either one HSCT or with standard disease-modifying therapy

You may not qualify if:

• History of non-compliance

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Johns Hopkins University: collaborator
• Children's National Research Institute: collaborator
• Emory University: collaborator
• University of Illinois at Chicago: collaborator
• Children's Healthcare of Atlanta: collaborator

Study Sites (5)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

NOT YET RECRUITING

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

NOT YET RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

NOT YET RECRUITING

National Institutes of Health Clinical Center

Bethesda, Maryland, 20814, United States

NOT YET RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-9000, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples for genetic testing to identify whether genes may predict health outcomes.

MeSH Terms

Conditions

Anemia, Sickle Cell; Lung Diseases; Kidney Diseases; Heart Diseases

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiratory Tract Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cardiovascular Diseases

Study Officials

• Michael R DeBaun, MD, MPH

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leshana Saint Jean, PhD

CONTACT

6158751992; leshana.saint.jean@vumc.org

Kristin Wuichet, PhD

CONTACT

6159366098; kristin.wuichet@vumc.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Medicine

Study Record Dates

• First Submitted: October 25, 2021
• First Posted: December 10, 2021
• Study Start: July 12, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (5)