Exercise in Child Health

Cystic Fibrosis Clinical Trial

— Project REACH  

Official title:

Revamping Exercise Assessments in Child Health (Project REACH)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05359991
• Other study ID #: 20195402
• Status: Recruiting
• Phase: N/A
• Start date: November 12, 2020
• Est. completion date: June 2024

Study information

• Verified date: March 2024
• Source: University of California, Irvine
• Contact: Peter Horvath, Ph.D.
• Phone: (714) 456-8248
• Email: phorvath[@]hs.uci.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: June 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• COVID-19
• Cystic Fibrosis
• Sickle Cell Disease

Intervention

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

Locations

Country	Name	City	State
United States	University of California, Irvine	Irvine	California

Sponsors (4)

Lead Sponsor	Collaborator
University of California, Irvine	Ann & Robert H Lurie Children's Hospital of Chicago, Children's Hospital Los Angeles, Children's Hospital of Orange County

Country where clinical trial is conducted

United States, 

References & Publications (17)

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. — View Citation

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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. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Physiol Rep. 2016 Jan;4(1). pii: e12680. doi: 10.14814/phy2.12680. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gas Exchange Variables	oxygen uptake	8 Months
Primary	Whole Body Lean Mass	Measured by Dual X-Ray Densitometry	8 Months
Primary	Physical Activity	Measured by Actigraphy	8 Months
Primary	Biomarkers	IGF-1	8 Months
Primary	Gene Expression	Circulating leukocyte gene expression associated with exercise	8 Months
Primary	Gas Exchange Variables	V?O2	8 Months
Primary	Gas Exchange Variables	Carbon dioxide output	8 Months
Primary	Gas Exchange Variables	V?CO2	8 Months
Primary	Gas Exchange Variables	ventilation	8 Months
Primary	Gas Exchange Variables	V?E	8 Months
Primary	Gas Exchange Variables	heart rate (HR)	8 Months
Primary	Fat Mass	Measured by Dual Energy X-Ray Absorptiometry	8 Months
Primary	% Body Fat	Measured by Dual X-Ray Densitometry	8 Months
Primary	Whole Body Bone Mineral Content	Measured by Dual X-Ray Densitometry	8 Months
Primary	Whole Body Bone Mineral Density	Measured by Dual X-Ray Densitometry	8 Months
Primary	Biomarkers	IL6	8 Months
Primary	Biomarkers	C-Reactive Protein	8 Months
Primary	Biomarkers	Glucose	8 Months
Primary	Biomarkers	insulin	8 Months
Primary	Biomarkers	lipid screen	8 Months
Primary	Biomarkers	lactate	8 Months
Primary	Biomarkers	CBC	8 Months
Primary	Gene Expression	Circulating Leukocyte Gene Expression Associated with Sickle Cell Anemia	8 Months
Primary	Gene Expression	Circulating Leukocyte Gene Expression Associated with Cystic Fibrosis	8 Months
Secondary	Behavioral responses to exercise	PROMIS Parent Fatigue Questionnaire	8 Months
Secondary	Standardized assessments	TANNER Staging Questionnaire	8 Months
Secondary	Behavioral responses to exercise	PROMIS Pediatric Fatigue Questionnaire	8 Months
Secondary	Behavioral responses to exercise	Project REACH NHANES PAQ Adapted Questionnaire	8 Months
Secondary	Behavioral responses to exercise	PEDSQL Fatigue Questionnaire	8 Months
Secondary	Behavioral responses to exercise	Appendices Questionnaire	8 Months
Secondary	Standardized assessments	Block Standardized FFQ	8 Months