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Sickle Cell Pro-Inflammatory Response to Interval Training Study (SPRINTS)

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ClinicalTrials.gov Identifier: NCT03653676
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : August 31, 2018
Sponsor:
Collaborators:
University of Illinois at Chicago
St. Jude Children's Research Hospital
Columbia University
University of California, Irvine
Information provided by (Responsible Party):
Robert I. Liem, Ann & Robert H Lurie Children's Hospital of Chicago

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.

Condition or disease Intervention/treatment
Sickle Cell Disease Other: Exercise Test (CIIT)

Detailed 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.

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Study Type : Observational
Estimated Enrollment : 140 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: The Pro-Inflammatory Effects of Acute Exercise in Children With Sickle Cell Anemia
Actual Study Start Date : January 2, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2022


Group/Cohort Intervention/treatment
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)
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
Children and adolescents without SCA or sickle cell trait randomized to either moderate or vigorous intensity exercise test (CIIT)
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).




Primary Outcome Measures :
  1. Biomarker- VCAM-1 [ Time Frame: Through study completion, approximately 2 years ]
    Change in soluble vascular cell adhesion molecule VCAM-1 in ng/mL


Secondary Outcome Measures :
  1. Biomarker - ICAM-1 [ Time Frame: Through study completion, approximately 2 years ]
    Change in intercellular adhesion molecule-1 in ng/mL

  2. Biomarker - PECAM-1 [ Time Frame: Through study completion, approximately 2 years ]
    Change in platelet endothelial cell adhesion molecule-1 in ng/mL

  3. Biomarker - L-selectin [ Time Frame: Through study completion, approximately 2 years ]
    Change in L-selectin in ng/mL

  4. Biomarker - E-selectin [ Time Frame: Through study completion, approximately 2 years ]
    Change in E-selectin in ng/mL

  5. Biomarker - P-selectin [ Time Frame: Through study completion, approximately 2 years ]
    Change in P-selectin in ng/mL

  6. Biomarker - IL-6 [ Time Frame: Through study completion, approximately 2 years ]
    Change in interleukin-6 in pg/mL

  7. Exercise spirometry [ Time Frame: Through study completion, approximately 2 years ]
    Forced expiratory volume in 1 second (FEV1 mesured in % of normal predicted value)

  8. Near infrared spectroscopy (NIRS) - total oxygen saturation [ Time Frame: Through study completion, approximately 2 years ]
    Near infrared spectroscopy (NIRS) derived measurements (total oxygen saturation (StO2) in the pre-frontal cortex and vastus lateralis muscle) in %

  9. Near infrared spectroscopy (NIRS) - oxygenated hemoglobin [ Time Frame: Through study completion, approximately 2 years ]
    Near infrared spectroscopy (NIRS) derived measurements (oxygenated hemoglobin in the pre-frontal cortex and vastus lateralis muscle) in %

  10. Near infrared spectroscopy (NIRS) - deoxygenated hemoglobin [ Time Frame: Through study completion, approximately 2 years ]
    Near infrared spectroscopy (NIRS) derived measurements (deoxygenated hemoglobin in the pre-frontal cortex and vastus lateralis muscle) in %

  11. Genomic studies [ Time Frame: Through study completion, approximately 2 years ]
    Gene and microRNA expression in mononuclear cells measured by fold change

  12. Asthma risk screening - ISAAC questionnaire [ Time Frame: Through study completion, approximately 2 years ]
    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)).

  13. Asthma risk screening - FeNO measurement [ Time Frame: Through study completion, approximately 2 years ]
    Exhaled nitric oxide (FeNO) in ppb)

  14. Asthma risk screening - Urinary Leukotrienes [ Time Frame: Through study completion, approximately 2 years ]
    Urine leukotriene (LTE4) in pg/mg)

  15. Eucapnic voluntary hyperventilation (EVH) spirometry [ Time Frame: Through study completion, approximately 2 years ]
    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.

  16. Adverse events [ Time Frame: Through study completion, approximately 2 years ]
    Safety outcomes including number of cardiopulmonary complications, vaso-occlusive pain or other adverse events related to exercise and EVH reported as incidence (number and %).

  17. Patient reported physical functioning - fatigue [ Time Frame: Through study completion, approximately 2 years ]
    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)

  18. Patient reported physical functioning - mobility [ Time Frame: Through study completion, approximately 2 years ]
    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)

  19. Patient reported physical activity level [ Time Frame: Through study completion, approximately 2 years ]
    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)


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.


Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03653676


Contacts
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Contact: Robert Liem, MD 312-227-4842 rliem@luriechildrens.org
Contact: Connie Casale, BS 312-227-4856 ccasale@luriechildrens.org

Locations
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United States, Illinois
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60608
Contact: Garett Griffith    312-996-9594    gjgriff@uic.edu   
Principal Investigator: Lewis Hsu, MD, PhD         
Sub-Investigator: Tracy Baynard, PhD         
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Connie Casale    312-227-4856    ccasale@luriechildrens.org   
Principal Investigator: Robert Liem, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Juan Grateron    212-304-7806    jg3751@cumc.columbia.edu   
Principal Investigator: Nancy Green, MD         
Sub-Investigator: Robert Garofano, EdD, RCEP         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Kristen Woodward    901-595-5685    kristen.woodward@st.jude.org   
Principal Investigator: Jane Hankins, MD         
Sub-Investigator: Kirsten Ness, PT, PhD         
Sponsors and Collaborators
Ann & Robert H Lurie Children's Hospital of Chicago
University of Illinois at Chicago
St. Jude Children's Research Hospital
Columbia University
University of California, Irvine
Investigators
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Principal Investigator: Robert Liem, MD Ann and Robert H. Lurie Childrens Hospital

Additional Information:
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Responsible Party: Robert I. Liem, Principal Investigator, Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier: NCT03653676     History of Changes
Other Study ID Numbers: 2017-881
First Posted: August 31, 2018    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Robert I. Liem, Ann & Robert H Lurie Children's Hospital of Chicago:
Sickle Cell Anemia
Sickle Cell Disease
Exercise
Fitness
Asthma
Inflammation

Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn