Exercise for Chronic Pediatric Conditions

(Project REACH Trial)

Overseen By Peter Horvath, Ph.D.

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Irvine

Must not be taking: Chronic medications

Disqualifiers: Substance abuse, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 months

240 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that chronic medication use is an exclusion criterion for healthy controls and those with a history of SARS-CoV-2 infection. It's best to discuss your specific medications with the trial coordinators.

What data supports the effectiveness of the treatment Exercise, Physical Activity, Workout, Fitness Training for chronic pediatric conditions?

Research shows that exercise can improve fitness levels and muscle strength in children with chronic conditions. For example, a study found that setting specific fitness goals led to significant improvements in cardiorespiratory fitness and strength in children at risk of metabolic issues. Additionally, tailored exercise interventions have been shown to enhance exercise capacity, endurance, and quality of life in children with various chronic diseases. ^{1 2 3 4 5}

Is exercise safe for children with chronic conditions?

Exercise is generally safe for children, including those with chronic conditions like congenital heart disease, when done appropriately. Studies show that exercise can help improve physical fitness and is recommended by health authorities, but it's important to follow specific guidelines and consult with healthcare providers. ^{6 7 8 9 10}

How is exercise different from other treatments for chronic pediatric conditions?

Exercise is unique because it not only helps alleviate symptoms of chronic conditions but also improves a child's overall quality of life and psychosocial development. Unlike medications, exercise can enhance physical fitness, reduce body fat, and improve functional ability, making it a holistic approach to managing chronic diseases in children. ^{11 12 13 14 15}

Eligibility Criteria

Children aged approximately 10-17 with cystic fibrosis, sickle cell disease, or past SARS-CoV-2 infection are eligible for this exercise study if they're in good health and have no other conditions that limit physical activity. They must be at a stage of puberty as defined by Tanner stages 1-5 and have physician approval to perform exercise tests.

Inclusion Criteria

I have sickle cell disease and am between 10 to 17 years old.

I have been diagnosed with Cystic Fibrosis based on genetic tests or sweat chloride levels.

I am between 10 and 17 years old.

Exclusion Criteria

I am receiving treatment for substance or alcohol abuse, or I use chronic medication.

PERC staff will decide if you are not fit for exercise because of SARS-CoV-2.

I have cystic fibrosis and am currently infected with either Burkholderia cenocepacia or Mycobacterium abscessus.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Cardiopulmonary Exercise Test (CPET) to measure cardiorespiratory responses, with blood sampling at multiple time points

8 months

Annual visits for exercise testing and blood sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment, including gene expression and body composition assessments

8 months

Treatment Details

Interventions

• Exercise

Trial Overview The REACH project is testing how children with chronic diseases respond to exercise. It aims to develop new ways of measuring the effects of physical activity on kids with genetic diseases like cystic fibrosis and sickle cell disease, as well as those affected by COVID-19.

Participant Groups

Group I: Children With Sickle Cell Disease (SCD) Experimental Treatment 1 Intervention

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.

Group II: Children With Documented History of SARS CoV-2 Infection Experimental Treatment 1 Intervention

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.

Group III: Children With Cystic Fibrosis (CF) Experimental Treatment 1 Intervention

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.

Group IV: Healthy Controls Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Children's Hospital of Orange County

Collaborator

Trials

38

Recruited

5,700+

Children's Hospital Los Angeles

Collaborator

Trials

257

Recruited

5,075,000+

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborator

Trials

275

Recruited

5,182,000+

Children's Hospital of Orange County (CHOC)

Collaborator

Trials

1

Recruited

240+

Children's Hospital of Los Angeles (CHLA)

Collaborator

Trials

2

Recruited

3,600+

Lurie Children's Hospital in Chicago

Collaborator

Trials

1

Recruited

240+

Findings from Research

A randomized controlled trial is being conducted to evaluate the effectiveness of a live-video-supervised exercise program for pediatric Fontan patients, aiming to improve their cardiac and physical capacity, muscle mass, strength, and endothelial function.

This innovative approach addresses the low adherence rates seen in traditional exercise interventions by using technology to provide supervised sessions, with the goal of reducing long-term morbidity and mortality in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and rationale of re-energize fontan: Randomized exercise intervention designed to maximize fitness in fontan patients. Selamet Tierney, ES., Palaniappan, L., Leonard, M., et al.[2023]

The Fitkids program included 2482 children with diverse demographics and medical diagnoses, highlighting the varied needs of children with chronic conditions or disabilities.

Participants showed significantly reduced aerobic fitness levels, as indicated by poor performance on the 6-minute walk test and half Bruce treadmill test, suggesting a need for targeted interventions to improve their fitness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fitkids exercise therapy program in the Netherlands. Kotte, EM., Winkler, AM., Takken, T.[2019]

Fitness testing in pediatric practice was successfully implemented with 580 participants, measuring cardiorespiratory fitness, strength, and flexibility, showing that it is feasible and effective.

Setting SMART goals led to significant improvements in cardiorespiratory fitness (11.9%) and strength (12.4%) in children at high risk for metabolic issues, although body mass index changes were not significantly affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Term Impact of Exercise Fitness Testing in a Pediatric Metabolic and Obesity Clinic: Initiative to Improve Health Care Quality. Vincent, HK., Bhavsar, P., Bernier, A.[2023]

A 6-week training program involving high-intensity cycling significantly improved aerobic and anaerobic fitness in children with mild-to-moderate asthma, with the training group showing an 18% increase in VO2max compared to 9% in the control group.

The study indicates that high-intensity exercise is safe and well-tolerated for asthmatic children, suggesting that anaerobic activities should be included in rehabilitation programs for better fitness outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Training of aerobic and anaerobic fitness in children with asthma. Counil, FP., Varray, A., Matecki, S., et al.[2022]

This study will investigate the specific limitations to physical activity in 72 children aged 6-18 with chronic diseases such as Fontan circulation, Broncho Pulmonary Dysplasia, Pompe disease, and inflammatory bowel disease, aiming to tailor interventions to their unique needs.

A 12-week personalized exercise intervention, potentially including dietary advice and psychological counseling, will be assessed for its effects on various health outcomes, including exercise capacity, quality of life, and muscle strength, providing insights into how to enhance physical activity in these children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study Protocol of the Exercise Study: Unraveling Limitations for Physical Activity in Children With Chronic Diseases in Order to Target Them With Tailored Interventions-A Randomized Cross Over Trial. Scheffers, LE., Helbing, WA., Utens, EMWJ., et al.[2022]

Exercise training is safe for children and adolescents with congenital heart disease, with no reported adverse events linked to the interventions across 6 trials involving 642 participants.

The training showed efficacy in improving physical fitness, with significant enhancements in exercise capacity and cardiorespiratory fitness in several studies, although the evidence quality is considered low to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of exercise training in children and adolescents with congenital heart disease: A systematic review and descriptive analysis. Anderson, CAJ., Suna, JM., Keating, SE., et al.[2023]

Children and adolescents are recommended to engage in 60 minutes of moderate to vigorous physical activity daily, including vigorous activities at least 3 days a week and strength training for muscles and bones also 3 days a week.

Despite the rising rates of childhood obesity and related health issues, many children do not meet these exercise guidelines, highlighting the need for education on the benefits and safety of physical activity for all children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric exercise: truth and/or consequences. Nettle, H., Sprogis, E.[2018]

A 5-year study involving 40 children with congenital heart defects showed that those who participated in a simple home exercise program during the first 3 months after surgery achieved normal physical fitness levels.

In contrast, children who did not engage in the postoperative training program remained significantly less active than their healthy peers, highlighting the importance of early exercise intervention for improving long-term physical activity in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative exercise training develops normal levels of physical activity in a group of children following cardiac surgery. Longmuir, PE., Tremblay, MS., Goode, RC.[2018]

Strength training can be safe and beneficial for children and adolescents when properly supervised and tailored to their developmental level, helping to improve strength, coordination, and overall fitness.

The review emphasizes the importance of pediatricians providing informed guidance on strength training programs, addressing both potential risks and the positive impacts on physical health and athletic performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strength training by children and adolescents. Bernhardt, DT., Gomez, J., Johnson, MD., et al.[2019]

A survey of 68 paediatric cardiac clinicians in the UK revealed that 36% had never given written exercise advice to children with congenital heart disease (CHD), highlighting a significant gap in communication about physical activity benefits.

Despite recognizing the importance of physical activity for CHD patients, many clinicians cited time constraints, lack of training, and uncertainty about recommendations as barriers to providing exercise advice, indicating a need for better education and resources in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A survey of exercise advice and recommendations in United Kingdom paediatric cardiac clinics. Williams, CA., Gowing, L., Horn, R., et al.[2018]

Exercise training significantly enhances cardiovascular fitness and quality of life in children aged 8-20 years with chronic respiratory diseases like asthma and cystic fibrosis, based on a meta-analysis of 24 studies involving 1009 participants.

While exercise showed a large effect on cardiovascular fitness (SMD=1.16) and quality of life (SMD=1.27), it had a negligible impact on lung function (SMD=0.02), indicating that exercise is more beneficial for overall fitness and well-being rather than directly improving lung function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise training on physical and psychosocial health in children with chronic respiratory disease: a systematic review and meta-analysis. Joschtel, B., Gomersall, SR., Tweedy, S., et al.[2023]

Youth with low physical activity and high body fat are at greater risk for cardiovascular issues, but daily physical activity can help reduce body fat and improve fitness levels.

Recent studies show that exercise therapy positively impacts aerobic capacity, functional ability, and quality of life in children with disabilities and chronic diseases, highlighting the importance of lifelong exercise interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity recommendations for children and adolescents with chronic disease. Morris, PJ.[2022]

Chronic diseases in children, such as cystic fibrosis and asthma, can lead to unnecessary restrictions on physical activities, which can negatively impact their quality of life.

Prescribing exercise programs for these children can help alleviate symptoms and promote psychosocial development, highlighting the importance of advocating for their right to participate in physical activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Children, Sports, and Chronic Disease. Goldberg, B.[2016]

A moderate intensity, progressive resistance training program for obese preadolescent children was implemented safely, with no reported injuries and full compliance over 10 weeks.

Significant reductions in weight, body mass index, and body fat were observed after 10 weeks, and these improvements were maintained at a 1-year follow-up, alongside increases in height and lean body mass.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inclusion of resistance exercise in a multidisciplinary outpatient treatment program for preadolescent obese children. Sothern, MS., Loftin, JM., Udall, JN., et al.[2019]

Children with chronic diseases or disabilities are generally less active than their healthy peers due to various biological, psychological, and social factors, which can negatively impact their health and disease outcomes.

The statement emphasizes the importance of individualized evaluations by experienced physicians to provide safe activity counseling and guidelines for children with conditions like juvenile arthritis, hemophilia, asthma, and cystic fibrosis, highlighting the potential health benefits of physical activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity recommendations for children with specific chronic health conditions: juvenile idiopathic arthritis, hemophilia, asthma, and cystic fibrosis. Philpott, JF., Houghton, K., Luke, A.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Design and rationale of re-energize fontan: Randomized exercise intervention designed to maximize fitness in fontan patients. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Fitkids exercise therapy program in the Netherlands. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Short-Term Impact of Exercise Fitness Testing in a Pediatric Metabolic and Obesity Clinic: Initiative to Improve Health Care Quality. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Training of aerobic and anaerobic fitness in children with asthma. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Study Protocol of the Exercise Study: Unraveling Limitations for Physical Activity in Children With Chronic Diseases in Order to Target Them With Tailored Interventions-A Randomized Cross Over Trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of exercise training in children and adolescents with congenital heart disease: A systematic review and descriptive analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Pediatric exercise: truth and/or consequences. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Postoperative exercise training develops normal levels of physical activity in a group of children following cardiac surgery. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Strength training by children and adolescents. [2019]

10. England pubmed.ncbi.nlm.nih.gov

A survey of exercise advice and recommendations in United Kingdom paediatric cardiac clinics. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Effects of exercise training on physical and psychosocial health in children with chronic respiratory disease: a systematic review and meta-analysis. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Physical activity recommendations for children and adolescents with chronic disease. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Children, Sports, and Chronic Disease. [2016]

14. United States pubmed.ncbi.nlm.nih.gov

Inclusion of resistance exercise in a multidisciplinary outpatient treatment program for preadolescent obese children. [2019]

15. United States pubmed.ncbi.nlm.nih.gov

Physical activity recommendations for children with specific chronic health conditions: juvenile idiopathic arthritis, hemophilia, asthma, and cystic fibrosis. [2022]