Exercise in Child Health

NCT05359991 | Recruiting DMC

• 1 other identifier: STUDY00000028 (20195402)
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis; Sickle Cell Disease; SARS CoV 2 Infection

Outcome Measures

Primary Outcomes (24)

• Gas Exchange Variables

  oxygen uptake

  8 Months

• Whole Body Lean Mass

  Measured by Dual X-Ray Densitometry

  8 Months

• Physical Activity

  Measured by Actigraphy

  8 Months

• Biomarkers

  IGF-1

  8 Months

• Gene Expression

  Circulating leukocyte gene expression associated with exercise

  8 Months

• Gas Exchange Variables

  V̇O2

  8 Months

• Gas Exchange Variables

  Carbon dioxide output

  8 Months

• Gas Exchange Variables

  V̇CO2

  8 Months

• Gas Exchange Variables

  ventilation

  8 Months

• Gas Exchange Variables

  V̇E

  8 Months

• Gas Exchange Variables

  heart rate (HR)

  8 Months

• Fat Mass

  Measured by Dual Energy X-Ray Absorptiometry

  8 Months

• % Body Fat

  Measured by Dual X-Ray Densitometry

  8 Months

• Whole Body Bone Mineral Content

  Measured by Dual X-Ray Densitometry

  8 Months

• Whole Body Bone Mineral Density

  Measured by Dual X-Ray Densitometry

  8 Months

• Biomarkers

  IL6

  8 Months

• Biomarkers

  C-Reactive Protein

  8 Months

• Biomarkers

  Glucose

  8 Months

• Biomarkers

  insulin

  8 Months

• Biomarkers

  lipid screen

  8 Months

• Biomarkers

  lactate

  8 Months

• Biomarkers

  CBC

  8 Months

• Gene Expression

  Circulating Leukocyte Gene Expression Associated with Sickle Cell Anemia

  8 Months

• Gene Expression

  Circulating Leukocyte Gene Expression Associated with Cystic Fibrosis

  8 Months

Secondary Outcomes (7)

• Behavioral responses to exercise

  8 Months

• Standardized assessments

  8 Months

• Behavioral responses to exercise

  8 Months

• Behavioral responses to exercise

  8 Months

• Behavioral responses to exercise

  8 Months

Study Arms (5)

Healthy Controls

ACTIVE COMPARATOR

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

Children With Documented History of SARS CoV-2 Infection

EXPERIMENTAL

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

Children With Sickle Cell Disease (SCD)

EXPERIMENTAL

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

Children With Cystic Fibrosis (CF)

EXPERIMENTAL

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

Children with Hyperlipidemia

EXPERIMENTAL

Cardiopulmonary Exercise Test (CPET) will be performed to measure cardiorespiratory responses in children with Children with hyperlipidema (Visit 1). 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 (Visit 2). The following procedures will occur: * The child will be in a fasted state. * An IV will be placed into the child's arm.

Other: Exercise

Interventions

Exercise OTHER

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

Children With Cystic Fibrosis (CF); Children With Documented History of SARS CoV-2 Infection; Children With Sickle Cell Disease (SCD); Children with Hyperlipidemia; Healthy Controls

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Irvine: lead
• Children's Hospital of Orange County: collaborator
• Children's Hospital Los Angeles: collaborator
• Ann & Robert H Lurie Children's Hospital of Chicago: collaborator

Study Sites (1)

University of California, Irvine

Irvine, California, 92697, United States

RECRUITING

Related Publications (17)

• Klentrou P. Influence of Exercise and Training on Critical Stages of Bone Growth and Development. Pediatr Exerc Sci. 2016 May;28(2):178-86. doi: 10.1123/pes.2015-0265. Epub 2016 Feb 17.

  PMID: 26884506 BACKGROUND

• Shay CM, Ning H, Daniels SR, Rooks CR, Gidding SS, Lloyd-Jones DM. Status of cardiovascular health in US adolescents: prevalence estimates from the National Health and Nutrition Examination Surveys (NHANES) 2005-2010. Circulation. 2013 Apr 2;127(13):1369-76. doi: 10.1161/CIRCULATIONAHA.113.001559. Epub 2013 Apr 1.

  PMID: 23547177 BACKGROUND

• Gates PE, Strain WD, Shore AC. Human endothelial function and microvascular ageing. Exp Physiol. 2009 Mar;94(3):311-6. doi: 10.1113/expphysiol.2008.043349. Epub 2008 Nov 28.

  PMID: 19042980 BACKGROUND

• Mielgo-Ayuso J, Aparicio-Ugarriza R, Castillo A, Ruiz E, Avila JM, Aranceta-Batrina J, Gil A, Ortega RM, Serra-Majem L, Varela-Moreiras G, Gonzalez-Gross M. Physical Activity Patterns of the Spanish Population Are Mostly Determined by Sex and Age: Findings in the ANIBES Study. PLoS One. 2016 Feb 25;11(2):e0149969. doi: 10.1371/journal.pone.0149969. eCollection 2016.

  PMID: 26914609 BACKGROUND

• Herman KM, Hopman WM, Sabiston CM. Physical activity, screen time and self-rated health and mental health in Canadian adolescents. Prev Med. 2015 Apr;73:112-6. doi: 10.1016/j.ypmed.2015.01.030. Epub 2015 Feb 4.

  PMID: 25660484 BACKGROUND

• Maher CA, Toohey M, Ferguson M. Physical activity predicts quality of life and happiness in children and adolescents with cerebral palsy. Disabil Rehabil. 2016;38(9):865-9. doi: 10.3109/09638288.2015.1066450. Epub 2015 Jul 28.

  PMID: 26218617 BACKGROUND

• Mutlu EK, Mutlu C, Taskiran H, Ozgen IT. Association of physical activity level with depression, anxiety, and quality of life in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2015 Nov 1;28(11-12):1273-8. doi: 10.1515/jpem-2015-0082.

  PMID: 26197465 BACKGROUND

• Pacheco DR, Silva MJ, Alexandrino AM, Torres RM. Exercise-related quality of life in subjects with asthma: a systematic review. J Asthma. 2012 Jun;49(5):487-95. doi: 10.3109/02770903.2012.680636. Epub 2012 May 3.

  PMID: 22554022 BACKGROUND

• Kohl HW 3rd, Craig CL, Lambert EV, Inoue S, Alkandari JR, Leetongin G, Kahlmeier S; Lancet Physical Activity Series Working Group. The pandemic of physical inactivity: global action for public health. Lancet. 2012 Jul 21;380(9838):294-305. doi: 10.1016/S0140-6736(12)60898-8.

  PMID: 22818941 BACKGROUND

• Nishi A, Milner DA Jr, Giovannucci EL, Nishihara R, Tan AS, Kawachi I, Ogino S. Integration of molecular pathology, epidemiology and social science for global precision medicine. Expert Rev Mol Diagn. 2016;16(1):11-23. doi: 10.1586/14737159.2016.1115346. Epub 2015 Dec 4.

  PMID: 26636627 BACKGROUND

• Briggs AM, Cross MJ, Hoy DG, Sanchez-Riera L, Blyth FM, Woolf AD, March L. Musculoskeletal Health Conditions Represent a Global Threat to Healthy Aging: A Report for the 2015 World Health Organization World Report on Ageing and Health. Gerontologist. 2016 Apr;56 Suppl 2:S243-55. doi: 10.1093/geront/gnw002.

  PMID: 26994264 BACKGROUND

• Chu P, Pandya A, Salomon JA, Goldie SJ, Hunink MG. Comparative Effectiveness of Personalized Lifestyle Management Strategies for Cardiovascular Disease Risk Reduction. J Am Heart Assoc. 2016 Mar 29;5(3):e002737. doi: 10.1161/JAHA.115.002737.

  PMID: 27025969 BACKGROUND

• Jimenez-Pavon D, Kelly J, Reilly JJ. Associations between objectively measured habitual physical activity and adiposity in children and adolescents: Systematic review. Int J Pediatr Obes. 2010;5(1):3-18. doi: 10.3109/17477160903067601.

  PMID: 19562608 BACKGROUND

• Tirakitsoontorn P, Nussbaum E, Moser C, Hill M, Cooper DM. Fitness, acute exercise, and anabolic and catabolic mediators in cystic fibrosis. Am J Respir Crit Care Med. 2001 Oct 15;164(8 Pt 1):1432-7. doi: 10.1164/ajrccm.164.8.2102045.

  PMID: 11704591 BACKGROUND

• Alvarado AM, Ward KM, Muntz DS, Thompson AA, Rodeghier M, Fernhall B, Liem RI. Heart rate recovery is impaired after maximal exercise testing in children with sickle cell anemia. J Pediatr. 2015 Feb;166(2):389-93.e1. doi: 10.1016/j.jpeds.2014.10.064. Epub 2014 Dec 2.

  PMID: 25477159 BACKGROUND

• Liem RI, Reddy M, Pelligra SA, Savant AP, Fernhall B, Rodeghier M, Thompson AA. Reduced fitness and abnormal cardiopulmonary responses to maximal exercise testing in children and young adults with sickle cell anemia. Physiol Rep. 2015 Apr;3(4):e12338. doi: 10.14814/phy2.12338.

  PMID: 25847915 BACKGROUND

• Schneiderman JE, Wilkes DL, Atenafu EG, Nguyen T, Wells GD, Alarie N, Tullis E, Lands LC, Coates AL, Corey M, Ratjen F. Longitudinal relationship between physical activity and lung health in patients with cystic fibrosis. Eur Respir J. 2014 Mar;43(3):817-23. doi: 10.1183/09031936.00055513. Epub 2013 Oct 31.

  PMID: 24176992 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis; Anemia, Sickle Cell; COVID-19

Interventions

Exercise

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Peter Horvath, Ph.D.

CONTACT

(714) 456-8248; phorvath@hs.uci.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 31, 2022
• First Posted: May 4, 2022
• Study Start: November 12, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 24, 2026

Record last verified: 2026-01

Locations

US (1)