Sickle Cell Pro-Inflammatory Response to Interval Training Study

Sickle Cell Disease Clinical Trial

— SPRINTS  

Official title:

The Pro-Inflammatory Effects of Acute Exercise in Children With Sickle Cell Anemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03653676
• Other study ID #: 2017-881
• Status: Recruiting
• Start date: January 2, 2018
• Est. completion date: December 2022

Study information

• Verified date: August 2021
• Source: Ann & Robert H Lurie Children's Hospital of Chicago
• Contact: Robert Liem, MD
• Phone: 312-227-4842
• Email: rliem[@]luriechildrens.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

The investigator's plan to evaluate the effect of acute exercise and exercise intensity on circulating systemic pro-inflammatory mediators and airway bronchoconstriction in SCA. The investigators hypothesize that regular exercise at moderate to vigorous intensity is safe for children with SCA and do not precipitate SCA-related symptoms. In this multicenter study, 70 non-asthmatic children with SCA and 70 controls without SCA will first undergo a maximal cardiopulmonary exercise test (CPET), then be randomized to an exercise challenge by controlled intensity interval training (CIIT) at either moderate or vigorous intensity (8 exercise bouts at 50% or 70% peak workload, respectively). The Investigator's Aims are to: 1) Determine the influence of exercise intensity on the acute inflammatory response to exercise, defined by an increase in soluble vascular cell adhesion molecule (VCAM) and other adhesion molecules, and 2) Define the effect of moderate to vigorous exercise on forced expiratory volume in 1 second (FEV1) and acute bronchoconstriction in children with SCA. The investigators will also explore exercise- induced changes in gene and microRNA expression in peripheral blood mononuclear cells, tissue oxygenation during exercise by near infrared spectroscopy as well as the role of hyperventilation in bronchoconstriction using eucapnic voluntary hyperventilation testing in a subset of participants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 2022
• Est. primary completion date: March 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 21 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Other:
• Exercise Test (CIIT)
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).

Locations

Country	Name	City	State
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Columbia University Medical Center	New York	New York

Sponsors (5)

Lead Sponsor	Collaborator
Ann & Robert H Lurie Children's Hospital of Chicago	Columbia University, St. Jude Children's Research Hospital, University of California, Irvine, University of Illinois at Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarker- VCAM-1	Change in soluble vascular cell adhesion molecule VCAM-1 in ng/mL	Through study completion, approximately 2 years
Secondary	Biomarker - ICAM-1	Change in intercellular adhesion molecule-1 in ng/mL	Through study completion, approximately 2 years
Secondary	Biomarker - PECAM-1	Change in platelet endothelial cell adhesion molecule-1 in ng/mL	Through study completion, approximately 2 years
Secondary	Biomarker - L-selectin	Change in L-selectin in ng/mL	Through study completion, approximately 2 years
Secondary	Biomarker - E-selectin	Change in E-selectin in ng/mL	Through study completion, approximately 2 years
Secondary	Biomarker - P-selectin	Change in P-selectin in ng/mL	Through study completion, approximately 2 years
Secondary	Biomarker - IL-6	Change in interleukin-6 in pg/mL	Through study completion, approximately 2 years
Secondary	Exercise spirometry	Forced expiratory volume in 1 second (FEV1 mesured in % of normal predicted value)	Through study completion, approximately 2 years
Secondary	Near infrared spectroscopy (NIRS) - total oxygen saturation	Near infrared spectroscopy (NIRS) derived measurements (total oxygen saturation (StO2) in the pre-frontal cortex and vastus lateralis muscle) in %	Through study completion, approximately 2 years
Secondary	Near infrared spectroscopy (NIRS) - oxygenated hemoglobin	Near infrared spectroscopy (NIRS) derived measurements (oxygenated hemoglobin in the pre-frontal cortex and vastus lateralis muscle) in %	Through study completion, approximately 2 years
Secondary	Near infrared spectroscopy (NIRS) - deoxygenated hemoglobin	Near infrared spectroscopy (NIRS) derived measurements (deoxygenated hemoglobin in the pre-frontal cortex and vastus lateralis muscle) in %	Through study completion, approximately 2 years
Secondary	Genomic studies	Gene and microRNA expression in mononuclear cells measured by fold change	Through study completion, approximately 2 years
Secondary	Asthma risk screening - ISAAC questionnaire	International Study of Asthma and Allergies in Childhood (ISAAC) screening questionnaire for rhinitis and eczema based on yes/no responses and point system to determine severity of condition (e.g. for rhinitis, 0 to 3 points (most severe); for eczema, 0 to 4 points (most severe)).	Through study completion, approximately 2 years
Secondary	Asthma risk screening - FeNO measurement	Exhaled nitric oxide (FeNO) in ppb)	Through study completion, approximately 2 years
Secondary	Asthma risk screening - Urinary Leukotrienes	Urine leukotriene (LTE4) in pg/mg)	Through study completion, approximately 2 years
Secondary	Eucapnic voluntary hyperventilation (EVH) spirometry	Forced expiratory volume in 1 second (FEV1 in % of normal predicted value) will be taken after EVH at 5, 10, 15, and 30 minutes to assess exercise induced bronchoconstriction in a subset of participants.	Through study completion, approximately 2 years
Secondary	Adverse events	Safety outcomes including number of cardiopulmonary complications, vaso-occlusive pain or other adverse events related to exercise and EVH reported as incidence (number and %).	Through study completion, approximately 2 years
Secondary	Patient reported physical functioning - fatigue	NIH PROMIS questionnaire for fatigue using appropriate raw summed and T scores with higher scores indicating worse fatigue (pediatric - raw 0 to 40, T score 30.3 to 84; parent proxy - raw 0 to 40, T score 34 to 85; adult - raw 8 to 40, T score 33.1 to 77.8)	Through study completion, approximately 2 years
Secondary	Patient reported physical functioning - mobility	NIH PROMIS questionnaire for mobility using appropriate raw summed, scale or T scores with higher scores indicating better mobility (pediatric - raw 0 to 32, T-score 15.2 to 58.5; adult - raw 8 to 40, T-score 20.9 to 59.7; parent proxy - raw 0 to 32, scale 14 to 56)	Through study completion, approximately 2 years
Secondary	Patient reported physical activity level	NHANES physical activity questionnaire for frequency of moderate versus vigorous physical activity in number of days in typical week (range 0 to 7 days with higher number indicating more days spent in moderate or vigorous activity) and time spent in typical day (0 to > 2 hours with higher number indicating more hours spent in moderate or vigorous activity)	Through study completion, approximately 2 years

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