Clinical trial NCT06661278: Evaluation of Exercise Testing and Physical Activity in Children and Adolescents Living With Inherited Arrhythmias
Official title: Evaluation of Free-living Physical Activity and the Assessment Tools Used to Support Pharmacological Therapy Titration and Exercise Prescription in Children and Adolescents Diagnosed With Inherited Arrhythmias
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Long QT Syndrome
Catecholaminergic Polymorphic Ventricular Tachycardia Type 1
Catecholaminergic Polymorphic Ventricular Tachycardia Type 2
Keywords: Children
Adolescents
Exercise
Physical activity
Exercise tolerance testing
Lead sponsor: Royal Brompton & Harefield NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Guy's and St Thomas' NHS Foundation Trust
First posted: 2024-10-28
Enrollment: 110
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Affected cohort: 60 children aged 6-16 years, diagnosed with inherited arrhythmias (IAS)

Unaffected cohort: 50 healthy children aged 6-16 years (siblings of affected children and those undergoing screening for inherited arrhythmias)

Brief summary: The goal of this observational study is to evaluate exercise testing and daily physical activity in children and adolescents who are diagnosed with an inherited arrhythmia.

The main question it aims to answer is: Does maximum heart rate during controlled exercise tolerance testing accurately reflect maximum heart rate and peak exercise levels during free living daily physical activity in children and adolescents diagnosed with an inherited arrhythmia?

Participants will:

* Complete routine exercise tolerance testing
* Record daily physical activity and exercise over two weeks, while wearing an activity and heart rate monitor and digit diary.
* Complete a physical activity questionnaire at the end of two weeks.

Detailed description: Exercise tolerance testing (ETT) using an exercise treadmill is a tool used to assess children's physical response to stress, which is thought to accurately reflect normal physiology during normal daily activities and can be used to:

* Evaluate heart rhythm and symptoms occurring during exercise.
* Evaluate children with a family history of sudden death and inherited heart conditions.
* Assess the response of medications prescribed to control heart rhythm.

The maximum heart rate achieved during ETT is used to estimate the effect of daily medications and to guide exercise prescription.

Originally designed to assess adult heart disease patients, ETTs were not intended for use in children. To accommodate the needs of children, shorter ETT protocols have been developed which increase the speed and/or incline of the treadmill quickly.

Despite this, many children rarely complete the full ETT protocol as they grow tired or develop other symptoms, which leads to them stopping exercise early, resulting in variable lengths of testing.

Children naturally increase exercise effort during day-to-day free-living physical activity (PA). Free-living PA is therefore thought to show a more accurate representation of the maximum heart rate (HR) children can achieve. Presently there is no strong evidence base to determine what children with an Inherited Arrhythmia (IA) (a genetically inherited heart condition which causes abnormalities in the heart rhythm) are doing in terms of daily free-living PA and exercise. The current recommendations used to prescribe exercise for this patient group are based on expert opinion and are not child specific. The study I propose supports the development of a greater evidence base to guide future exercise prescription and better tailored medications.

The study aims to:

* To compare the maximum HR achieved during controlled ETT with the maximum HR achieved during daily free-living PA and exercise, to see if these are different.
* To assess three different exercise testing protocols for children, and identify if one is better than the others at estimating maximum heart rate compared with free-living PA.
* To investigate the actual versus reported PA children engage in using a questionnaire and digital PA diary.

To achieve these aims, the study will recruit children (aged 6-16 years) diagnosed with an IA and who are able to run on an exercise treadmill, plus a healthy control group (unaffected siblings, or children undergoing screening).

A clinical ETT will be performed as part of routine care. Each participant will be given a wearable PA monitoring device to monitor free-living PA over two-weeks. The device will record parameters such as electrocardiogram, HR, and step count. PA will also be recorded digitally to capture type and length of activity they engage in, and estimated intensity.

At the end of the two-weeks, participants will complete a questionnaire about their PA which will be compared with the data obtained during the monitoring period. Parents will be invited to support younger children with questionnaire and digital recording completion.

A study lay advisory group will be established including children and their parents affected by an IA. They will advise on study design and development of all patient-facing information throughout the study.

The results of the study will be discussed with lay advisory groups who will advise on the best ways to share results with the wider public but will include publication in high quality Open Access journals and dissemination at relevant national and international conferences. Invitations will also be provided to the voluntary support groups involved in the early planning phases to publish the results on their websites

Eligibility criteria: Inclusion Criteria:

Affected cohort

* Male and female children
* Aged 6-16 years
* Diagnosed with long QT syndrome or catecholaminergic polymorphic ventricular tachycardia
* Treated with beta-blocker and/or sodium channel blockade
* Able to complete a treadmill ETT

Healthy cohort

* Male and female children
* Aged 6-16 years
* Siblings of affected children (gene negative)
* Undergoing IAS screening
* Able to complete a treadmill ETT

Exclusion Criteria:

* Children aged less than 6 years
* Adults, 17 years of age and above
* Unable to run on an exercise treadmill due to physical limitations.
* Individuals unable to speak or understand English, due to no translation service available.
* Pregnancy

Primary outcomes:
measure: Correlation of maximum heart rate during clinical exercise tolerance test and daily physical activity
timeFrame: Baseline assessment (week one of study assessments)
measure: Physical activity questionnaire
timeFrame: End of two-week physical activity monitoring (week two of study assessments)
Secondary outcomes:
measure: Heart rate assessment during exercise tolerance testing
timeFrame: Baseline assessment (week one of study assessment)
measure: Comparison of exercise tolerance testing protocols
timeFrame: Immediately after the intervention
Other outcomes:
Locations:
city: London Borough of Sutton
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
affiliation: Royal Brompton & Harefield NHS Foundation Trust
name: Catherine E Renwick
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chockalingam P, Wilde AA. Inherited arrhythmia syndromes leading to sudden cardiac death in the young: a global update and an Indian perspective. Indian Heart J. 2014 Jan-Feb;66 Suppl 1(Suppl 1):S49-57. doi: 10.1016/j.ihj.2013.11.008. Epub 2013 Dec 17.
citation: Zarain-Herzberg A, Estrada-Aviles R, Fragoso-Medina J. Regulation of sarco(endo)plasmic reticulum Ca2+-ATPase and calsequestrin gene expression in the heart. Can J Physiol Pharmacol. 2012 Aug;90(8):1017-28. doi: 10.1139/y2012-057. Epub 2012 Jul 11.
citation: Gibbons RJ, Balady GJ, Beasley JW, Bricker JT, Duvernoy WF, Froelicher VF, Mark DB, Marwick TH, McCallister BD, Thompson PD, Winters WL Jr, Yanowitz FG, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr, Lewis RP, O'Rourke RA, Ryan TJ. ACC/AHA guidelines for exercise testing: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). Circulation. 1997 Jul 1;96(1):345-54. doi: 10.1161/01.cir.96.1.345. No abstract available.
citation: Mellor GJ, Behr ER. Cardiac channelopathies: diagnosis and contemporary management. Heart. 2021 Jun 11;107(13):1092-1099. doi: 10.1136/heartjnl-2019-316026. No abstract available.
citation: Cheung CC, Laksman ZW, Mellor G, Sanatani S, Krahn AD. Exercise and Inherited Arrhythmias. Can J Cardiol. 2016 Apr;32(4):452-8. doi: 10.1016/j.cjca.2016.01.007. Epub 2016 Jan 14.
citation: Bruce RA, Blackmon JR, Jones JW, Strait G. Exercising testing in adult normal subjects and cardiac patients. 1963. Ann Noninvasive Electrocardiol. 2004 Jul;9(3):291-303. doi: 10.1111/j.1542-474X.2004.93003.x. No abstract available.
citation: Sagray E, Allison TG, Wackel PL. Is a high-intensity exercise test better than a graded exercise test in eliciting exercise-related arrhythmias? HeartRhythm Case Rep. 2021 May 15;7(8):549-552. doi: 10.1016/j.hrcr.2021.05.001. eCollection 2021 Aug. No abstract available.
citation: Duff DK, De Souza AM, Human DG, Potts JE, Harris KC. A novel treadmill protocol for exercise testing in children: the British Columbia Children's Hospital protocol. BMJ Open Sport Exerc Med. 2017 Apr 22;3(1):e000197. doi: 10.1136/bmjsem-2016-000197. eCollection 2017.
citation: van der Cammen-van Zijp MH, Ijsselstijn H, Takken T, Willemsen SP, Tibboel D, Stam HJ, van den Berg-Emons RJ. Exercise testing of pre-school children using the Bruce treadmill protocol: new reference values. Eur J Appl Physiol. 2010 Jan;108(2):393-9. doi: 10.1007/s00421-009-1236-x. Epub 2009 Oct 11.
citation: CAVAGNA GA, SAIBENE FP, MARGARIA R. MECHANICAL WORK IN RUNNING. J Appl Physiol. 1964 Mar;19:249-56. doi: 10.1152/jappl.1964.19.2.249. No abstract available.
citation: Schepens B, Willems PA, Cavagna GA. The mechanics of running in children. J Physiol. 1998 Jun 15;509 ( Pt 3)(Pt 3):927-40. doi: 10.1111/j.1469-7793.1998.927bm.x.
citation: Van Hooren B, Fuller JT, Buckley JD, Miller JR, Sewell K, Rao G, Barton C, Bishop C, Willy RW. Is Motorized Treadmill Running Biomechanically Comparable to Overground Running? A Systematic Review and Meta-Analysis of Cross-Over Studies. Sports Med. 2020 Apr;50(4):785-813. doi: 10.1007/s40279-019-01237-z.
citation: Schoffl I, Ehrlich B, Stanger S, Rottermann K, Dittrich S, Schoffl V. Exercise Field Testing in Children: A New Approach for Age-Appropriate Evaluation of Cardiopulmonary Function. Pediatr Cardiol. 2020 Aug;41(6):1099-1106. doi: 10.1007/s00246-020-02359-2. Epub 2020 May 9.
citation: Pelliccia A, Sharma S, Gati S, Back M, Borjesson M, Caselli S, Collet JP, Corrado D, Drezner JA, Halle M, Hansen D, Heidbuchel H, Myers J, Niebauer J, Papadakis M, Piepoli MF, Prescott E, Roos-Hesselink JW, Graham Stuart A, Taylor RS, Thompson PD, Tiberi M, Vanhees L, Wilhelm M; ESC Scientific Document Group. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J. 2021 Jan 1;42(1):17-96. doi: 10.1093/eurheartj/ehaa605. No abstract available.
citation: Priori SG, Blomstrom-Lundqvist C. 2015 European Society of Cardiology Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death summarized by co-chairs. Eur Heart J. 2015 Nov 1;36(41):2757-9. doi: 10.1093/eurheartj/ehv445.
citation: Maron BJ, Chaitman BR, Ackerman MJ, Bayes de Luna A, Corrado D, Crosson JE, Deal BJ, Driscoll DJ, Estes NA 3rd, Araujo CG, Liang DH, Mitten MJ, Myerburg RJ, Pelliccia A, Thompson PD, Towbin JA, Van Camp SP; Working Groups of the American Heart Association Committee on Exercise, Cardiac Rehabilitation, and Prevention; Councils on Clinical Cardiology and Cardiovascular Disease in the Young. Recommendations for physical activity and recreational sports participation for young patients with genetic cardiovascular diseases. Circulation. 2004 Jun 8;109(22):2807-16. doi: 10.1161/01.CIR.0000128363.85581.E1.
citation: Chaput JP, Willumsen J, Bull F, Chou R, Ekelund U, Firth J, Jago R, Ortega FB, Katzmarzyk PT. 2020 WHO guidelines on physical activity and sedentary behaviour for children and adolescents aged 5-17 years: summary of the evidence. Int J Behav Nutr Phys Act. 2020 Nov 26;17(1):141. doi: 10.1186/s12966-020-01037-z.
citation: Moss AJ, Zareba W, Hall WJ, Schwartz PJ, Crampton RS, Benhorin J, Vincent GM, Locati EH, Priori SG, Napolitano C, Medina A, Zhang L, Robinson JL, Timothy K, Towbin JA, Andrews ML. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation. 2000 Feb 15;101(6):616-23. doi: 10.1161/01.cir.101.6.616.
citation: Ussher MH, Owen CG, Cook DG, Whincup PH. The relationship between physical activity, sedentary behaviour and psychological wellbeing among adolescents. Soc Psychiatry Psychiatr Epidemiol. 2007 Oct;42(10):851-6. doi: 10.1007/s00127-007-0232-x. Epub 2007 Jul 17.