Sickle Cell Pro-Inflammatory Response to Interval Training Study

NCT03653676 | Completed DMC

• 1 other identifier: 2017-881
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 3

Brief Summary

Recommendations for exercise prescription currently do not exist for individuals with sickle cell anemia (SCA) despite the known impact that SCA-related complications has on physical functioning and fitness. A major barrier to increasing physical activity in SCA is the concern that the well-described inflammatory effects of exercise could precipitate or exacerbate complications such as vaso-occlusive pain or airway bronchoconstriction (i.e. exercise-induced asthma). Although the investigator's preliminary data suggest that increasing physical activity may be beneficial rather than harmful in children with SCA, the pro-inflammatory effects associated with repeated bouts of moderate to vigorous exercise remain poorly understood in this population. The long term goal is to address the safety and health impact of regular exercise in children with SCA. This proposal would help establish the safety of moderate to vigorous intensity exercise in children with SCA and importantly, will inform the design of future clinical trials focused on exercise training as a transformative strategy to improve fitness and overall well-being in this population.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Anemia; Sickle Cell Disease; Exercise; Fitness; Asthma; Inflammation

Outcome Measures

Primary Outcomes (1)

• Biomarker- VCAM-1

  Change in soluble vascular cell adhesion molecule VCAM-1 in ng/mL

  Through study completion, approximately 2 years

Secondary Outcomes (19)

• Biomarker - ICAM-1

  Through study completion, approximately 2 years

• Biomarker - PECAM-1

  Through study completion, approximately 2 years

• Biomarker - L-selectin

  Through study completion, approximately 2 years

• Biomarker - E-selectin

  Through study completion, approximately 2 years

• Biomarker - P-selectin

  Through study completion, approximately 2 years

Study Arms (2)

Subjects with SCA

Children and adolescents with SCA confirmed by hemoglobin analysis randomized to either moderate or vigorous intensity exercise test (CIIT)

Other: Exercise Test (CIIT)

Controls without SCA

Children and adolescents without SCA or sickle cell trait randomized to either moderate or vigorous intensity exercise test (CIIT)

Other: Exercise Test (CIIT)

Interventions

Exercise Test (CIIT) OTHER

The CIIT exercise test will consist of 8 bouts (2 minute each) of constant workload cycling with rest periods (1 minute each) in between each bout of exercise. Subjects and controls will be randomized to either a moderate intensity or vigorous intensity, defined as 50% or 70% of the maximal workload achieved on the maximal cardiopulmonary exercise test (CPET).

Controls without SCA; Subjects with SCA

Eligibility Criteria

• Age: 10 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

This study will plan to enroll a total of 70 non-asthmatic subjects with SCA and 70 controls without SCA across all sites. Male or female, aged 10 years to 21 years old. Diagnosis of hemoglobin SS or S/Beta0 thalassemia confirmed by hemoglobin electrophoresis. Children and young adults on hydroxyurea are eligible but must be at steady state at time of enrollment, defined as stable dosing for at least 2 months, without anticipated changes in dose during study participation. Race and age-matched controls without SCA or sickle cell trait will be recruited among friends, relatives, siblings or individuals from similar communities to minimize confounding socio-demographic variables that may impact baseline fitness. Controls will be required to be 10 through 21 years of age.

You may qualify if:

• Provide signed and dated informed consent form
• Willing to comply with all study procedures and be available for the duration of the study
• Male or female, aged 10 years to 21 years old
• Diagnosis of hemoglobin SS or S/Beta0 thalassemia confirmed by hemoglobin electrophoresis

You may not qualify if:

• Inability to perform CPET due to physical limitation (e.g. severe hip osteonecrosis or stroke)
• Enrollment on chronic transfusion program
• History of exercise-induced arrhythmia or syncope
• Diagnosis of asthma, defined as physician diagnosis or use of daily asthma medications
• Known exercise-induced bronchoconstriction, defined as physician diagnosis by exercise challenge test
• History of any cardiac diagnosis precluding exercise testing, unless cleared by a cardiologist
• Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study

Sponsors & Collaborators

• Ann & Robert H Lurie Children's Hospital of Chicago: lead
• University of Illinois at Chicago: collaborator
• St. Jude Children's Research Hospital: collaborator
• Columbia University: collaborator
• University of California, Irvine: collaborator

Study Sites (3)

University of Illinois at Chicago

Chicago, Illinois, 60608, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (1)

• Cohen RT, Hankins JS, Ness KK, Hsu LL, Baynard T, Tang A, Radom-Aizik S, Guerrero K, Rodeghier M, Liem RI. Acute Exercise Challenge and Airway Dynamics in Youth With Sickle Cell Anemia: A Multicenter Study. Am J Hematol. 2025 Dec 20. doi: 10.1002/ajh.70170. Online ahead of print.

  PMID: 41422377 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

In this study, blood specimens will be collected at baseline and as part of pre and post CIIT exercise challenge. These studies will include routine clinical tests as well as biomarkers of inflammation and cellular adhesion. In a subset of participants at Lurie Children's, samples for genomic studies will be collected pre and post CIIT exercise challenge.

MeSH Terms

Conditions

Anemia, Sickle Cell; Motor Activity; Asthma; Inflammation

Interventions

Exercise Test

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; Behavior; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques

Study Officials

• Robert Liem, MD

  Ann and Robert H. Lurie Childrens Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: August 31, 2018
• Study Start: January 2, 2018
• Primary Completion: March 17, 2023
• Study Completion: March 17, 2023
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)