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Exercise in Child Health (Project REACH)

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ClinicalTrials.gov Identifier: NCT05359991
Recruitment Status : Recruiting
First Posted : May 4, 2022
Last Update Posted : May 4, 2022
Sponsor:
Collaborators:
Children's Hospital of Orange County (CHOC)
Children's Hospital of Los Angeles (CHLA)
Lurie Children's Hospital in Chicago
Information provided by (Responsible Party):
Dan Cooper, University of California, Irvine

Brief Summary:

This study is a cooperative investigation funded by the NIH. The project is a collaboration among three major NIH Clinical Translational Science Awardees: 1) UCI (lead site with its affiliate CHOC), 2) Northwestern University (with its affiliate Lurie Children's Hospital), and 3) USC (with its affiliate Children's Hospital of Los Angeles).

There is an increasing number of children who, through medical advances, now survive diseases and conditions that were once fatal, but which remain chronic and debilitating. A major challenge to improve both the immediate and long term care and health of such children has been the gap in our understanding of how to assess the biological effects of exercise. Like otherwise healthy children, children with chronic diseases and disabilities want to be physically active. The challenge is to determine what constitutes safe and beneficial level of physical activity when the underlying disease or condition [e.g., cystic fibrosis (CF) or sickle cell disease (SCD)] imposes physiological constraints on exercise that are not present in otherwise healthy children. Current exercise testing protocols were based on studies of athletes and high performing healthy individuals and were designed to test limits of performance at very high-intensity, unphysiological, maximal effort. These approaches are not optimal for children and adolescents with disease and disability. This project (REACH-Revamping Exercise Assessment in Child Health) is designed to address this gap. Cohorts of children will be identified with two major genetic diseases (CF and SCD) and measure exercise responses annually as they progress from early puberty to mid or late puberty over a 3-4year period. In addition, in the light of the pandemic, a group of children will be added who were affected by SARS-CoV-2 and investigate their responses to exercise. SARS-CoV-2 has similar long-term symptoms than CF and SCD have. Novel approaches to assessing physiological responses to exercise using advanced data analytics will be examined in relation to metrics of habitual physical activity, circulating biomarkers of inflammation and growth, leukocyte gene expression, and the impact of the underlying CF, SCD or SARS-CoV-2 condition. The data from this study will help to develop a toolkit of innovative metrics for exercise testing that will be made available to the research and clinical community.


Condition or disease Intervention/treatment Phase
Cystic Fibrosis Sickle Cell Disease SARS CoV 2 Infection Other: Exercise Not Applicable

Detailed Description:

New, generalizable approaches are needed for measuring physical fitness and activity across a spectrum of pediatric health and disease.

Exercise in children and adolescents is not merely play but is an essential component of growth and development. Children are among the most spontaneously physically active human beings. It is not surprising that participation in PA (Physical Activity) is a major determinant of health across the lifespan and health-related quality of life in both healthy children and in children with chronic diseases. Despite this essential biologic role for PA, children have not been spared the relentless reduction in levels of PA that is creating a crisis in health care in our nation and throughout the world. Recognition of the enormous morbidity and cost of physical inactivity-related diseases, such as atherosclerosis, type 2 diabetes, and osteoporosis, has spurred new policy initiatives targeting preventive medicine early in life. The concept of pediatric origins of adult health and disease is gaining scientific merit, highlighting the need to transform existing notions of how to evaluate health in a growing child. A physically inactive (even normal weight) child may have no symptoms of disease, but evidence of deterioration in vascular health may already be present. As era of population health management and precision medicine are approaching, the notion of what it means to be a healthy child must change and include robust metrics of physical fitness.

Equally worrisome is that the deleterious health effects of physical inactivity and poor fitness are exacerbated in children with chronic disease and/or disabilities or with environmental-lifestyle conditions like obesity. Children with diseases or conditions previously associated with mortality during the first two decades of life (e.g., SCD, CF) are living longer due to remarkable advances in research and care, but are often unable to achieve levels of PA and fitness associated with health benefits in otherwise healthy children. Not surprisingly, the healthspan [the period of life free from serious chronic diseases and disability of children with chronic diseases is threatened not only by the underlying disease, but by the compounding effects of insufficient PA and sedentary behavior. Increasing PA and fitness is feasible, but has proven quite challenging to implement in a systematic manner. Once a pattern of physical inactivity and a sedentary lifestyle is established, a vicious cycle ensues, in which constraints on PA harm immediate health and contribute to lifelong health impairment ranging from cardiovascular and metabolic disease to osteoporosis. Exactly what constitutes ideal physical fitness in a child with a chronic condition remains unknown. Finding beneficial levels of PA in children with chronic disease or disability is challenging because the optimal range of exercise is much narrower than in a healthy child. Finally, as a result of the COVID-19 pandemic a sizable number of children are experiencing long-term effects such as fatigue, and will be included in our study. Similar to children with CF and SCD, studies of exercise and physical activity will provide insight into disease mechanisms and possible therapies.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Revamping Exercise Assessments in Child Health (Project REACH)
Estimated Study Start Date : May 15, 2022
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2024


Arm Intervention/treatment
Active Comparator: Healthy Controls

Cardiopulmonary Exercise Test (CPET) will be performed to measure cardiorespiratory responses in healthy controls. Exercise will consist of up to 8, 2 minutes bouts of constant work rate cycle ergometry with 1 minute resting intervals between each exercise bout. A subgroup of children will be asked to allow the investigators to obtain blood samples during the exercise session. The following procedures will occur:

  • The child will be in a fasted state.
  • An IV will be placed into the child's arm.
  • Blood sampling will be taken at 4 time points; baseline, and the end of exercise, and at 30 and 60 minutes post exercise.
Other: Exercise
Cardiopulmonary Exercise Testing (CPET) will be used with Multiple Brief Exercise Bouts (MBEB) in order to obtain the necessary data to yield information on the study outcome variables

Experimental: Children With Documented History of SARS CoV-2 Infection

Cardiopulmonary Exercise Test (CPET) will be performed to measure cardiorespiratory responses in children with a documented history of SARS CoV-2 Infection. Exercise will consist of up to 8, 2 minutes bouts of constant work rate cycle ergometry with 1 minute resting intervals between each exercise bout. A subgroup of children will be asked to allow the investigators to obtain blood samples during the exercise session. The following procedures will occur:

  • The child will be in a fasted state.
  • An IV will be placed into the child's arm.
  • Blood sampling will be taken at 4 time points; baseline, and the end of exercise, and at 30 and 60 minutes post exercise.
Other: Exercise
Cardiopulmonary Exercise Testing (CPET) will be used with Multiple Brief Exercise Bouts (MBEB) in order to obtain the necessary data to yield information on the study outcome variables

Experimental: Children With Sickle Cell Disease (SCD)

Cardiopulmonary Exercise Test (CPET) will be performed to measure cardiorespiratory responses in children with Children With Sickle Cell Disease (SCD). Exercise will consist of up to 8, 2 minutes bouts of constant work rate cycle ergometry with 1 minute resting intervals between each exercise bout. A subgroup of children will be asked to allow the investigators to obtain blood samples during the exercise session. The following procedures will occur:

  • The child will be in a fasted state.
  • An IV will be placed into the child's arm.
  • Blood sampling will be taken at 4 time points; baseline, and the end of exercise, and at 30 and 60 minutes post exercise.
Other: Exercise
Cardiopulmonary Exercise Testing (CPET) will be used with Multiple Brief Exercise Bouts (MBEB) in order to obtain the necessary data to yield information on the study outcome variables

Experimental: Children With Cystic Fibrosis (CF)

Cardiopulmonary Exercise Test (CPET) will be performed to measure cardiorespiratory responses in children with Children With Cystic Fibrosis (CF). Exercise will consist of up to 8, 2 minutes bouts of constant work rate cycle ergometry with 1 minute resting intervals between each exercise bout. A subgroup of children will be asked to allow the investigators to obtain blood samples during the exercise session. The following procedures will occur:

  • The child will be in a fasted state.
  • An IV will be placed into the child's arm.
  • Blood sampling will be taken at 4 time points; baseline, and the end of exercise, and at 30 and 60 minutes post exercise.
Other: Exercise
Cardiopulmonary Exercise Testing (CPET) will be used with Multiple Brief Exercise Bouts (MBEB) in order to obtain the necessary data to yield information on the study outcome variables




Primary Outcome Measures :
  1. Gas Exchange Variables [ Time Frame: 8 Months ]
    oxygen uptake

  2. Whole Body Lean Mass [ Time Frame: 8 Months ]
    Measured by Dual X-Ray Densitometry

  3. Physical Activity [ Time Frame: 8 Months ]
    Measured by Actigraphy

  4. Biomarkers [ Time Frame: 8 Months ]
    IGF-1

  5. Gene Expression [ Time Frame: 8 Months ]
    Circulating leukocyte gene expression associated with exercise

  6. Gas Exchange Variables [ Time Frame: 8 Months ]
    V̇O2

  7. Gas Exchange Variables [ Time Frame: 8 Months ]
    Carbon dioxide output

  8. Gas Exchange Variables [ Time Frame: 8 Months ]
    V̇CO2

  9. Gas Exchange Variables [ Time Frame: 8 Months ]
    ventilation

  10. Gas Exchange Variables [ Time Frame: 8 Months ]
    V̇E

  11. Gas Exchange Variables [ Time Frame: 8 Months ]
    heart rate (HR)

  12. Fat Mass [ Time Frame: 8 Months ]
    Measured by Dual Energy X-Ray Absorptiometry

  13. % Body Fat [ Time Frame: 8 Months ]
    Measured by Dual X-Ray Densitometry

  14. Whole Body Bone Mineral Content [ Time Frame: 8 Months ]
    Measured by Dual X-Ray Densitometry

  15. Whole Body Bone Mineral Density [ Time Frame: 8 Months ]
    Measured by Dual X-Ray Densitometry

  16. Biomarkers [ Time Frame: 8 Months ]
    IL6

  17. Biomarkers [ Time Frame: 8 Months ]
    C-Reactive Protein

  18. Biomarkers [ Time Frame: 8 Months ]
    Glucose

  19. Biomarkers [ Time Frame: 8 Months ]
    insulin

  20. Biomarkers [ Time Frame: 8 Months ]
    lipid screen

  21. Biomarkers [ Time Frame: 8 Months ]
    lactate

  22. Biomarkers [ Time Frame: 8 Months ]
    CBC

  23. Gene Expression [ Time Frame: 8 Months ]
    Circulating Leukocyte Gene Expression Associated with Sickle Cell Anemia

  24. Gene Expression [ Time Frame: 8 Months ]
    Circulating Leukocyte Gene Expression Associated with Cystic Fibrosis


Secondary Outcome Measures :
  1. Behavioral responses to exercise [ Time Frame: 8 Months ]
    PROMIS Parent Fatigue Questionnaire

  2. Standardized assessments [ Time Frame: 8 Months ]
    TANNER Staging Questionnaire

  3. Behavioral responses to exercise [ Time Frame: 8 Months ]
    PROMIS Pediatric Fatigue Questionnaire

  4. Behavioral responses to exercise [ Time Frame: 8 Months ]
    Project REACH NHANES PAQ Adapted Questionnaire

  5. Behavioral responses to exercise [ Time Frame: 8 Months ]
    PEDSQL Fatigue Questionnaire

  6. Behavioral responses to exercise [ Time Frame: 8 Months ]
    Appendices Questionnaire

  7. Standardized assessments [ Time Frame: 8 Months ]
    Block Standardized FFQ



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Sickle Cell Disease

  • Tanner 1-5, corresponding approximately to ages 10-17 y/o
  • SCD diagnosis including all relevant genotypes
  • Determined to be in relatively good health as a patient with SCD with no complications from SCD that would render participation the study unadvisable
  • No evidence of other disease or disability that would impair participation in PA
  • Physician permission to perform CPET
  • BMI within the average range for age and condition

Cystic Fibrosis

  • Confirmed diagnosis of CF based on either two CF-causing mutations and/or a sweat chloride concentration of > 60 mmol/l after a positive newborn screening test or on two separate occasions
  • Tanner 1-5 corresponding approximately to ages 10-17 y/o as documented by a licensed independent provider at screening, or by a validated self-assessment tool
  • Determined to be in relatively good health as a patient with CF with no complications from CF that would render participation the study unadvisable as determined by a physician. Examples include history of submassive or massive hemoptysis or moderate to severe pulmonary hypertension.
  • BMI in the average range for age and condition
  • No evidence of other disease or disability that would impair participation in PA

Comparison (Healthy control)

  • Tanner 1-5 corresponding approximately to ages 10-17 y/o
  • Determined to be in good health by pre-participation history and physical examination performed by primary care providers or PERC staff
  • BMI and PA participation (by history) in the average range for age
  • No evidence of disease or disability that would impair participation in PA

Comparison (SARS-CoV-2)

  • Tanner 1-5 corresponding approximately to ages 10-17 y/o
  • Documented SARS-CoV-2 infection
  • Capable of doing exercise as determined by primary care providers or PERC a medical officer

Exclusion Criteria:

Sickle Cell Disease Treatment for substance or alcohol abuse

  • Requiring chronic monthly transfusions
  • Other conditions that preclude exercise such as neuromotor disease, heart disease, or any other condition that would prevent a child from participating in PA

Cystic Fibrosis Treatment for substance or alcohol abuse

  • Other conditions that preclude exercise (such as neuromotor disease, heart disease, or any other condition that would prevent a child from participating in PA)
  • FEV1 < 40% predicted based on Global Lung Index equations
  • Current infection with Burkholderia cenocepacia or Mycobacterium abscessus

Comparison (Healthy control) Treatment for substance or alcohol abuse or chronic medication use • Determination by PERC staff of unsuitability for exercise

Comparison (SARS-CoV-2) Treatment for substance or alcohol abuse or chronic medication use

• Determination by PERC staff of unsuitability for exercise


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): NCT05359991


Contacts
Layout table for location contacts
Contact: Peter Horvath, Ph.D. (714) 456-8248 phorvath@hs.uci.edu

Locations
Layout table for location information
United States, California
University of California, Irvine Recruiting
Irvine, California, United States, 92697
Contact: Shlomit Radom-Aizik, Ph.D.    949-824-2584    saizik@hs.uci.edu   
Contact: Dan Cooper, M.D.    (949) 824-1923    dcooper@hs.uci.edu   
Sponsors and Collaborators
University of California, Irvine
Children's Hospital of Orange County (CHOC)
Children's Hospital of Los Angeles (CHLA)
Lurie Children's Hospital in Chicago
Publications:

Layout table for additonal information
Responsible Party: Dan Cooper, Professor, University of California, Irvine
ClinicalTrials.gov Identifier: NCT05359991    
Other Study ID Numbers: 2019-5402
First Posted: May 4, 2022    Key Record Dates
Last Update Posted: May 4, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Cystic Fibrosis
Anemia, Sickle Cell
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections