Home-based Complex Intervention for Children With Ataxia Telangiectasia

Ataxia Telangiectasia Clinical Trial

Official title:

Exploring Effectiveness, Feasibility, and Acceptability of a Novel Home-based Complex Intervention for Children With Ataxia Telangiectasia: a Pilot Randomised Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05692622
• Other study ID #: 3756
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2023
• Est. completion date: July 31, 2024

Study information

• Verified date: November 2023
• Source: University of Plymouth
• Contact: Lisa Bunn, PhD
• Phone: +44 1752 588800
• Email: lisa.bunn[@]plymouth.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ataxia telangiectasia is a rare, genetic and progressive condition with no known cure. Therapies present a mainstream management option and have the potential to offer optimisation of fitness and general health. This pilot RCT aims to explore the effectiveness, feasibility, and acceptability of a co-produced home-based complex exercise intervention for children with ataxia telangiectasia. The study was designed through broad consultation with a collaborative of children and young people with A-T including family members, therapists, clinicians and researchers, called the A-Team collaborative (https://osf.io/edzn3/)

Description:

Ataxia telangiectasia (A-T) usually presents in early childhood, primarily affecting the pulmonary, neurological and immunological systems. World-wide prevalence estimates vary between 1 in 40,000 and 1 in 100,000 live births. A-T typically presents with cerebellar ataxia in early childhood, generally before the age of four years, such that by early teenage most patients require a wheelchair for mobility. Oculomotor, extrapyramidal and peripheral nervous system problems occur in later childhood and adolescence. Lung disease and difficulties with feeding, swallowing and nutrition are also common. A-T also carries a high risk of malignancy, and life-expectancy for individuals with A-T is decreased, with survival time of 25 years.

People living with A-T require coordinated multi-disciplinary care to optimally manage their complex needs. Symptomatic management and rehabilitation is advocated to improve quality of life and minimize complications that could increase morbidity and mortality. However, the feasibility and acceptability of allied health interventions and outcome measures for this population group are under-researched. Parents participating in a research engagement meeting reported being unclear about how best to deal with the signs and symptoms of A-T at home, how to find help and how and when to access support. This uncertainty is echoed by therapists treating children and adults with ataxia. Evidence is lacking about what type of therapy is needed and how it might be best delivered. The investigators intend to address these concerns and perspectives by investigating the effectiveness, feasibility, and acceptability of a home-based exercise intervention that offers therapeutic interventions for the impairments, activity limitations, and participation restrictions related to A-T.

An extensive review undertaken at the beginning of this overall project scoping the evidence on care and management of A-T provided by allied health professionals and nurses, identified a range of interventions that reportedly positively impact A-T related impairments, together with quality of life, indicating that outcomes can be improved for this population. Through i) considerable and robust engagement to date with key stakeholders (including parents, older children and young adults with A-T, physiotherapists, occupational therapists and charity workers), and ii) evidence from other research studies involving pediatric populations with the same or similar health conditions which indicate the potential benefits of yoga and breathing exercises in optimizing health, fitness and wellbeing, the investigators have identified a strong need for this study.

Objectives

1. Assess the effectiveness of the complex home-based exercise intervention on physical function, respiratory muscle strength, participation, and quality of life

2. Investigate the feasibility of the complex home-based exercise intervention in terms of:

1. online and remote delivery by a multi-disciplinary health profession team with an allied health-professional lead (exploring factors such as undertaking online assessment, supervising exercise and wider trial activities, supporting participants and their families and monitoring safety)

2. participant and families' abilities to undertake the exercises (exploring factors such as frequency and duration of exercises, and length of the intervention programme)

3. use of a digital platform for accessing exercise movies and sharing feedback and experience with research team and other participating families

3. Investigate the feasibility of the home-based clinical trial design in terms of:

1. participant recruitment and online consent taking

2. online and remote delivery of home-based intervention

3. online assessments at four different time points and engagement with extensive trial-based battery of outcome measures

4. conducting exit interviews online

5. use of the digital platform for trial involvement

4. Determine intervention fidelity in terms of:

1. the degree to which the intervention is implemented as intended

2. frequency, intensity and duration of exercise interventions

3. what were the barriers faced (if any) and how were they addressed?

4. what were the facilitators (if any) for undertaking the exercises?

5. Explore the perception and experiences of parents/legal guardians and children with A-T undertaking the exercises regarding engagement, effectiveness, and acceptability of the intervention

6. Analyse the data of this pilot study to

1. Select the most appropriate outcome measure and inform design of an onward RCT

2. Make recommendations about whether a fully powered trial may be undertaken depending on whether the feasibility of the home-based exercise intervention and the home-based clinical trial design is established.

3. Inform the power calculation for the subsequent RCT using the outcome data from this study

The project that this study is a part of, is funded by Action for A-T and supported for PPIE and recruitment by the A-T Society. Dr Lisa Bunn is the principal investigator and Dr Tracey Parkin the co-principal investigator of this project. A list of all the collaborators of this project is available on the following link- https://osf.io/edzn3/

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: July 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 11 Years

Eligibility

Inclusion Criteria:

• Diagnosis of A-T confirmed clinically

• Aged 4-11 years

• Able to walk independently (with no or only intermittent support) over 10 metres and stand unaided for 1 minute

• Able to communicate in English either independently or with the assistance of their parent/legal guardian (where parent/guardian is able to communicate in English) or using a translator arranged by the participating family

• Has the ability to assent and parents/legal guardians have the ability to give consent on their child's behalf

Exclusion Criteria:

• Those with other/additional diagnoses thought by the study team to probably compromise the intervention, e.g. with significant intellectual disability

• Currently undergoing cancer therapies or acutely unwell

• Children who are participants of another trial/intervention programme

• Non-UK based families

Related Conditions & MeSH terms

• Ataxia
• Ataxia Telangiectasia
• Cerebellar Ataxia
• Telangiectasis

Intervention

Other:
• Whole-body exercise and respiratory exercise
The study involves an 8-week intervention involving whole-body and respiratory exercises. The whole-body exercise component will involve doing exercises while watching a total of 32 Comic Kids yoga movies. These movies have been adapted to suit the needs and abilities of the target population. For the first 7 weeks of intervention, children will be provided with 4 yoga movies for each week, providing around 67 minutes of exercise in each week. In the last week of intervention, children will have the choice to practice any 4 exercises of their choice from the 28 movies. The respiratory exercise component will involve watching a 10-minute-long movie that involves practicing different styles of breathing and breath holding. Participants will be provided a respiratory trainer to use while practicing these breathing exercises. Children will be asked to practice these breathing exercises by watching the movie at least 2 days each week.

Locations

Country	Name	City	State
United Kingdom	University of Plymouth	Plymouth

Sponsors (1)

Lead Sponsor	Collaborator
University of Plymouth

Country where clinical trial is conducted

United Kingdom, 

References & Publications (17)

Amirifar P, Ranjouri MR, Yazdani R, Abolhassani H, Aghamohammadi A. Ataxia-telangiectasia: A review of clinical features and molecular pathology. Pediatr Allergy Immunol. 2019 May;30(3):277-288. doi: 10.1111/pai.13020. Epub 2019 Mar 20. — View Citation

Broccoletti T, Del Giudice E, Cirillo E, Vigliano I, Giardino G, Ginocchio VM, Bruscoli S, Riccardi C, Pignata C. Efficacy of very-low-dose betamethasone on neurological symptoms in ataxia-telangiectasia. Eur J Neurol. 2011 Apr;18(4):564-70. doi: 10.1111/j.1468-1331.2010.03203.x. Epub 2010 Sep 14. — View Citation

Cassidy E, Reynolds F, Naylor S, De Souza L. Using interpretative phenomenological analysis to inform physiotherapy practice: an introduction with reference to the lived experience of cerebellar ataxia. Physiother Theory Pract. 2011 May;27(4):263-77. doi: 10.3109/09593985.2010.488278. Epub 2010 Aug 26. — View Citation

Felix E, Gimenes AC, Costa-Carvalho BT. Effects of inspiratory muscle training on lung volumes, respiratory muscle strength, and quality of life in patients with ataxia telangiectasia. Pediatr Pulmonol. 2014 Mar;49(3):238-44. doi: 10.1002/ppul.22828. Epub 2013 Aug 19. — View Citation

Galantino ML, Galbavy R, Quinn L. Therapeutic effects of yoga for children: a systematic review of the literature. Pediatr Phys Ther. 2008 Spring;20(1):66-80. doi: 10.1097/PEP.0b013e31815f1208. — View Citation

Hartley H, Carter B, Bunn L, Pizer B, Lane S, Kumar R, Cassidy E. E-Survey of Current International Physiotherapy Practice for Children with Ataxia Following Surgical Resection of Posterior Fossa Tumour. J Rehabil Med Clin Commun. 2019 Dec 30;2:1000020. doi: 10.2340/20030711-1000020. eCollection 2019. — View Citation

Kepenek-Varol B, Gurses HN, Icagasioglu DF. Effects of Inspiratory Muscle and Balance Training in Children with Hemiplegic Cerebral Palsy: A Randomized Controlled Trial. Dev Neurorehabil. 2022 Jan;25(1):1-9. doi: 10.1080/17518423.2021.1905727. Epub 2021 Apr 1. — View Citation

McGrath-Morrow SA, Gower WA, Rothblum-Oviatt C, Brody AS, Langston C, Fan LL, Lefton-Greif MA, Crawford TO, Troche M, Sandlund JT, Auwaerter PG, Easley B, Loughlin GM, Carroll JL, Lederman HM. Evaluation and management of pulmonary disease in ataxia-telangiectasia. Pediatr Pulmonol. 2010 Sep;45(9):847-59. doi: 10.1002/ppul.21277. — View Citation

Nissenkorn A, Borgohain R, Micheli R, Leuzzi V, Hegde AU, Mridula KR, Molinaro A, D'Agnano D, Yareeda S, Ben-Zeev B. Development of global rating instruments for pediatric patients with ataxia telangiectasia. Eur J Paediatr Neurol. 2016 Jan;20(1):140-6. doi: 10.1016/j.ejpn.2015.09.002. Epub 2015 Sep 25. — View Citation

Perlman SL, Boder Deceased E, Sedgewick RP, Gatti RA. Ataxia-telangiectasia. Handb Clin Neurol. 2012;103:307-32. doi: 10.1016/B978-0-444-51892-7.00019-X. No abstract available. — View Citation

Reiman A, Srinivasan V, Barone G, Last JI, Wootton LL, Davies EG, Verhagen MM, Willemsen MA, Weemaes CM, Byrd PJ, Izatt L, Easton DF, Thompson DJ, Taylor AM. Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours. Br J Cancer. 2011 Aug 9;105(4):586-91. doi: 10.1038/bjc.2011.266. Epub 2011 Jul 26. — View Citation

Ross LJ, Capra S, Baguley B, Sinclair K, Munro K, Lewindon P, Lavin M. Nutritional status of patients with ataxia-telangiectasia: A case for early and ongoing nutrition support and intervention. J Paediatr Child Health. 2015 Aug;51(8):802-7. doi: 10.1111/jpc.12828. Epub 2015 Feb 6. — View Citation

Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM. Ataxia telangiectasia: a review. Orphanet J Rare Dis. 2016 Nov 25;11(1):159. doi: 10.1186/s13023-016-0543-7. — View Citation

Russo I, Cosentino C, Del Giudice E, Broccoletti T, Amorosi S, Cirillo E, Aloj G, Fusco A, Costanzo V, Pignata C. In ataxia-teleangiectasia betamethasone response is inversely correlated to cerebellar atrophy and directly to antioxidative capacity. Eur J Neurol. 2009 Jun;16(6):755-9. doi: 10.1111/j.1468-1331.2009.02600.x. — View Citation

Tai G, Corben LA, Woodcock IR, Yiu EM, Delatycki MB. Determining the Validity of Conducting Rating Scales in Friedreich Ataxia through Video. Mov Disord Clin Pract. 2021 Apr 6;8(5):688-693. doi: 10.1002/mdc3.13204. eCollection 2021 Jul. — View Citation

Taylor et al. Ataxia-telangiectasia in children Guidance on diagnosis and clinical care. Ataxia-Telangiectasia Society. 2014; 1-31

van Os NJH, Haaxma CA, van der Flier M, Merkus PJFM, van Deuren M, de Groot IJM, Loeffen J, van de Warrenburg BPC, Willemsen MAAP; A-T Study Group. Ataxia-telangiectasia: recommendations for multidisciplinary treatment. Dev Med Child Neurol. 2017 Jul;59(7):680-689. doi: 10.1111/dmcn.13424. Epub 2017 Mar 20. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Scale for the Assessment and Rating of Ataxia; to assess change in score between different time points	Scale for the Assessment and Rating of Ataxia (SARA) is a reliable and valid clinical scale used to measure the severity of ataxia. It has eight categories with accumulative score ranging from 0 (no ataxia) to 40 (most severe ataxia); where higher score indicates worse outcomes. SARA was selected as the primary outcome measure as it is a validated tool that is widely used in paediatric population. It has also been successfully used in A-T population in the context of clinical trials of intervention and is validated for remote assessment.	Early start group assessments at baseline, week 1, week 9, and week 25; delayed start group assessments at baseline, week 1, week 9, week 17,and week 25
Secondary	Spirometry to measure slow vital capacity; to assess change in scores between different time points	A spirometer (MIR Spirobank smart spirometer) will be used to measure the respiratory muscle strength. It measures lung function, specifically the volume of air inspired and expired by the lungs. The investigators will use this test to measure slow vital capacity (SVC). SVC is the volume of air expired, through an unforced maneuver; where higher score indicates better outcomes	Early start group assessments at baseline, week 1, week 9, and week 25; delayed start group assessments at baseline, week 1, week 9, week 17,and week 25
Secondary	Spirometry to measure forced vital capacity; to assess change in scores between different time points	A spirometer (MIR Spirobank smart spirometer) will be used to measure the respiratory muscle strength. It measures lung function, specifically the volume of air inspired and expired by the lungs. The investigators will use this test to measure forced vital capacity (FVC). FVC is the maximum amount of air that can be forcibly exhaled from lungs after fully inhaling; where higher score indicates better outcomes.	Early start group assessments at baseline, week 1, week 9, and week 25; delayed start group assessments at baseline, week 1, week 9, week 17,and week 25
Secondary	Spirometry to measure forced expiratory volume in the first second; to assess change in scores between different time points	A spirometer (MIR Spirobank smart spirometer) will be used to measure the respiratory muscle strength. It measures lung function, specifically the volume of air inspired and expired by the lungs. The investigators will use this test to measure forced expiratory volume in the first second (FEV1). FEV1 is the volume of air (in liters) exhaled in the first second during forced exhalation after maximal inspiration; where higher score indicates better outcomes.	Early start group assessments at baseline, week 1, week 9, and week 25; delayed start group assessments at baseline, week 1, week 9, week 17,and week 25
Secondary	Spirometry to measure peak expiratory flow; to assess change in scores between different time points	A spirometer (MIR Spirobank smart spirometer) will be used to measure the respiratory muscle strength. It measures lung function, specifically the volume of air inspired and expired by the lungs. The investigators will use this test to measure peak expiratory flow (PEF). PEF is the volume of air forcefully expelled from the lungs in one quick exhalation; where higher score indicates better outcomes.	Early start group assessments at baseline, week 1, week 9, and week 25; delayed start group assessments at baseline, week 1, week 9, week 17,and week 25
Secondary	Pediatric Evaluation of Disability Inventory Computer Adaptive Test; to assess change in scores between different time points	Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) measures abilities in the domains of daily activities, mobility, social/cognitive, and responsibility. The domains of daily activities, mobility, and social/cognitive are rated on a 4 point difficulty scale with responses ranging from 'Unable' to 'Easy'; where higher score indicates better outcomes. The responsibility domain is rated on a 5 point scale with responses ranging from 'Adult/caregiver has full responsibility; the child does not take any responsibility' to 'Child takes full responsibility without any direction, supervision or guidance from an adult/caregiver'; where higher score indicates better outcomes.	Early start group assessments at baseline, week 1, week 9, and week 25; delayed start group assessments at baseline, week 1, week 9, week 17,and week 25
Secondary	EuroQuol-5Dimensions-Youth scale; to assess change in scores between different time points	EuroQuol-5Dimensions-Youth (EQ-5D-Y) measures quality of life in the following dimensions of health: mobility, looking after myself, doing usual activities, having pain or discomfort, and feeling worried, sad or unhappy. Each dimension has 3 levels: no problems, some problems, and extreme problems; based on the response, scores are assigned between 1 to 3, where higher score indicates worse outcomes.	Early start group assessments at baseline, week 1, week 9, and week 25; delayed start group assessments at baseline, week 1, week 9, week 17,and week 25