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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how exercise affects children with chronic conditions such as cystic fibrosis (CF), sickle cell disease (SCD), and those who have had COVID-19. Exercise tests measure how these children's bodies respond to physical activity. The goal is to develop better methods to test and improve exercise plans for them. Children with CF or SCD, or those who have experienced COVID-19 and can exercise without issues, might be suitable candidates for this study. As an unphased trial, this study offers a unique opportunity for children to contribute to research that could enhance exercise plans for others with similar conditions.

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 prior data suggests that this exercise protocol is safe for children with chronic conditions?

Research shows that exercise is generally safe for children with conditions like cystic fibrosis (CF), a history of COVID-19, and sickle cell disease (SCD). For children with CF, studies indicate that exercise rarely causes side effects, making it a safe way to boost fitness and health.

In children who have had COVID-19, most do not experience heart or lung problems from mild infections, suggesting that exercise is safe for them too.

For those with sickle cell disease, recent research suggests that controlled exercise does not cause problems and is well tolerated, indicating it is generally safe and can be helpful.

Overall, exercise appears to be a safe and beneficial activity for kids with these chronic conditions, improving their health and quality of life. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the exercise protocol being tested because it offers a non-invasive way to boost health in children with chronic conditions like cystic fibrosis, past SARS-CoV-2 infection, and sickle cell disease. Unlike conventional treatments that often rely on medication, this approach focuses on improving cardiorespiratory fitness through structured exercise, potentially offering fewer side effects. Additionally, the study aims to gather important data on how exercise impacts blood markers, providing insights that could lead to personalized exercise recommendations for these conditions.

What evidence suggests that this trial's exercise treatments could be effective for chronic pediatric conditions?

This trial will evaluate the effects of exercise on children with chronic conditions, including cystic fibrosis (CF), sickle cell disease (SCD), and those with a history of COVID-19 infection. Research has shown that exercise can be very helpful for these groups. Participants in the CF arm may experience improved lung function, fitness, and overall quality of life through regular exercise, which also strengthens muscles and heart health. In the arm for children with a history of COVID-19, exercise can improve heart and lung fitness and general health, addressing the reduced activity levels seen during the pandemic. For those in the SCD arm, light to moderate exercise is generally safe and can aid in muscle growth. Although some debate exists, exercise is usually seen as a beneficial addition to treatment plans for these conditions. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2945676/

Exercise Training in Children and Adolescents with Cystic ...

Regular exercise training is associated with improved aerobic and anaerobic capacity, higher pulmonary function, and enhanced airway mucus clearance.

2.

mdpi.com

mdpi.com/2227-9067/12/7/831

The Impact of Physical Activity on Clinical Outcomes in ...

Emerging evidence supports the role of physical exercise in improving lung function, aerobic capacity, and quality of life in pediatric CF patients.

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2950273X25000268

The effect of endurance, resistance and concurrent training ...

The purpose of this study was to determine the effects of three exercise-training programs on respiratory capacity and pulmonary function in patients with CF.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9690212/

Effectiveness of Physical Exercise Interventions on ...

Conclusions: Exercise interventions in children and adults with CF are effective in improving muscle strength, cardiovascular capacity, and respiratory muscle ...

5.

cysticfibrosisjournal.com

cysticfibrosisjournal.com/article/S1569-1993(21)02110-X/fulltext

The effectiveness of exercise interventions to increase ...

Physical activity (PA) and exercise have numerous benefits in Cystic Fibrosis (CF) including improved lung function, exercise capacity and ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9361297/

Physical activity and exercise training in cystic fibrosis - PMC

Side effects of physical activity are rare, so it can be considered safe in CF (Ruf 2010). Why it is important to do this review. This review aims to provide ...

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1526054209000396

Exercise and physical activity in children with cystic fibrosis

Higher levels of exercise capacity have been reported to be important for survival in patients with CF. Several studies have demonstrated an association between ...

8.

cochranelibrary.com

cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002768.pub5/full

Physical activity and exercise training in cystic fibrosis

Side effects of physical activity are rare, so it can be considered safe in CF (Ruf 2010). Why it is important to do this review. This review ...

9.

jpeds.com

jpeds.com/article/S0022-3476(00)51946-5/fulltext

Home-based exercise programs in cystic fibrosis: Are they ...

This 1-year program resulted in major improvements in forced vital capacity, FEV1, and aerobic fitness.