Hydrotherapy for Health in Boys and Adolescents With Duchenne Muscular Dystrophy
Phase: NA
Conditions: Duchenne Muscular Dystrophy
Sponsor: Lancashire Teaching Hospitals NHS Foundation Trust

 
Lancashire Teaching Hospitals 
NHS Foundation Trust 
 
 
 
CENTRE FOR HEALTH RESEARCH AND INNOVATION 
Protocol – version 3, 22 August 2023 
 
Title: 
Hydrotherapy for health in boys and adolescents with Duchenne muscular dystrophy 
 
Short Title: 
Hydrotherapy in DMD 
 
Study Team & Collaborations: 
Chief investigator: Dr Christian De Goede, Consultant Paediatric Neurologist, 
Lancashire Teaching Hospitals NHS Trust. Christian is a consultant paediatric 
neurologist with a keen interest in research, working closely with local universities. He is 
the lead for paediatric neuromuscular service in Lancashire and South Cumbria. He has 
worked on a number of collaborations with MMU, looking at activity and pain in children and 
adults with muscular dystrophy. Christian will lead the clinical side of the project with his 
team as a principal investigator. 
Co-Investigator: Dr Christopher Morse, Reader in Exercise Physiology, Department 
of Sports and Exercise Sciences, Manchester Metropolitan University. Christopher is 
a Reader in Exercise Physiology based at MMU Cheshire. His research looks at how 
neuromuscular function is affected by old age, lifelong conditions and physical activity. He 
has collaborated with the Neuromuscular Centre to undertake research in exercise, 
physiotherapy, diet and physical activity in adults with muscular dystrophy. Chris will be the 
academic lead for the study.  
Dr Petra Kolić, Senior Lecturer in Sports Coaching. Petra is a qualitative researcher 
investigating sociological aspects of health and wellbeing related to physical activity. Petra 
will conduct and analyse the qualitative interviews drawing upon 100s of hours of interview 
experience from her previous studies.  
Paula Sugden, Paediatric Research Nurse, Lancashire Teaching Hospitals NHS 
Trust. Paula works as a research nurse in the Child Health Department at Royal Preston 
Hospital. She has a wide role in the set up and management of research studies in 
children, and advocating research in our trust. She has been closely involved in the 
development and running of a trial looking at a new device to help children who wet the 
bed, and is about to start an exciting study looking at determinants of activity in children 
with muscle conditions. Supporting the clinical physiotherapist, Paula will be involved in the 
set up recruitment and management of the study.  
Natalie Mattos-Harris, Paediatric Research Nurse, Lancashire Teaching Hospitals 
NHS Trust. Natalie is a nurse in Child Health Department at Royal Preston Hospital. She is 
a research nurse, and also works as a neonatal nurse on the level 3 neonatal unit. She has 
been involved with a number of studies in children and neonates. Together with Paula, 
Natalie is about to start an exciting study looking at determinants of activity in children with 
muscle conditions. Supporting the clinical physiotherapist, Natalie will be involved in the set 
up recruitment and management of the study.  
Dr Kina Bennett, Research Operations Manager, Lancashire Teaching Hospitals NHS 
Trust. Kina represents the LTHTR trust as the sponsor for this study.  

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
 
 
Background (Literature review): 
 
There is a doubling of body fat (BF%) in young males with Duchenne Muscular Dystrophy 
(DMD) (Mayo et al., 2012), which may represent a significant contributory factor to co-
morbidities associated with this untreatable neuromuscular condition.  In adults with DMD 
and BMD we have found that, a higher BF% is associated with impaired glucose tolerance 
(Bostock et al., 2018) and lower perceived quality of life (QoL, Jacques, Stockley, 
Onambele-Pearson, et al., 2019).  Similarly, boys and adolescents with DMD have lower 
perceived QoL (Kohler et al., 2005), and can show evidence of mental health issues 
(Steele et al., 2008) commonly associated with progressive disability.  This progressive 
physical impairment, coupled with high levels of bodily pain (Hunt et al., 2016), likely 
contributes to boys and adolescents with DMD having lower daily physical activity levels 
and subsequently higher BF% and BMI than age matched boys without DMD (McDonald et 
al., 2005). Furthermore, an accumulating BF% in boys and adolescents with DMD may 
accentuate functional impairments such as lower limb weakness, as anti-gravity muscles 
are having to overcome an increasing body mass.  
Within boys with DMD, hydrotherapy is recommended (Bushby et al., 2005), yet in contrast 
to other neuromuscular conditions, within DMD there is scant evidence that hydrotherapy 
benefits QoL, pain and mobility. These quantifiable outcome measures have all shown 
benefit from longitudinal hydrotherapy in other populations including fybromyalgia, 
osteoarthritis, stroke and spinal muscle atrophy (Karjalainen et al., 1999; de Mattos et al., 
2016; Marinho-Buzelli et al., 2014). Within DMD, data is limited to small participant 
numbers, with some benefit of hydrotherapy shown in 1, 6 or 8 boys,  compared to 2-6 
boys not receiving the treatment (Honório et al., 2013; Honório, 2011; Hind et al., 2017). 
Where smaller groups of data are presented e.g., 8 boys with DMD receiving hydrotherapy, 
the focus was on 6-minute walk distance, rather than QoL or pain, and was again limited to 
comparisons with 2 control participants (Hind et al., 2017). In contrast, within Spinal muscle 
atrophy, improvements in QoL have been reported with frequent hydrotherapy (Cunha et 
al., 1996).   
Despite evidence that low intensity exercise may benefit, or at least not negatively impact, 
physical function and daily pain in DMD (Hunt et al., 2016; Jansen et al., 2013), there is at 
present a lack of evidence to suggest that those with DMD should undertake hydrotherapy, 
despite favourable anecdote (MDUK, 2015) and case reports.  Previously, we have 
identified a modest metabolic response following low intensity hand cycling in non-
ambulatory men with DMD (Morse et al., 2018). This cardiorespiratory impact was 
however, limited to those with the most functional upper limbs. Specifically, of those 
completing the study 2 men aged 18 and 20 were able to increase their metabolic rate to a 
level that would induce a meaningful health benefit. It could be hypothesized therefore, that 
young males (aged 6-18) with DMD have the potential to induce health benefits from active 
hydrotherapy movements. In contrast, those with limited mobility or active musculature, 
may experience benefits from passive hydrotherapy (e.g. pain and joint mobility). An 
exercise diary will be recorded for every hydrotherapy session, and with a sufficient sample 
of 20 participants, it will be possible to analyse the results of the study as a single 
intervention group with exercise intensity as a covariable to outcome adaptation, consistent 
with our previous sedentary behaviour interventions in other populations (Ryan et al., 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
2018). This project therefore seeks to: 1) undertake a hydrotherapy intervention in boys 
and adolescents with DMD and 2) conduct qualitative Patient and Parent interviews to 
understand the potential barriers and hidden benefits to hydrotherapy not captured in our 
outcome measures.  
Research Objective: 
It is hypothesised that undertaking hydrotherapy will result in a beneficial change in the primary 
outcomes of QoL, bodily pain, and body composition, and secondary outcomes of physical 
function (e.g. Range of motion strength, and upper limb function), where possible.  
The aim of this study is to determine whether hydrotherapy can mitigate some of the weight 
gain, bodily pain, lower QoL and functional impairments associated with progression of 
DMD in young males. 
Potential outcomes include:  
1) improvements in all outcome measures as a result of undertaking hydrotherapy 
(increased lean muscle mass, reduced body fat; improved functional measures (e.g. 
strength), activities of daily living, ROM; improved quality of life, and lowered bodily pain).  
2) no change in outcome measures-following hydrotherapy but a relative slowing of the 
decline observed during the “control period”.   
3) outcome measures continue to deteriorate at the same rate as the control period. 
4) a worsening of outcome measures compared to the control period. 
 
Objectives and Specific Aims: 
Outcomes 
This project will yield 4 experimental journal articles. 
1. The impact of hydrotherapy on body composition and muscle mass in boys with DMD 
2. The impact of hydrotherapy on QoL and bodily pain in boys with DMD 
3. The impact of hydrotherapy on muscle function and activities of daily living in boys with 
DMD 
4. Practical considerations and barriers to hydrotherapy in young people with DMD, a 
qualitative review of interviews with parents, carers and those with DMD. 
As the first hydrotherapy study within DMD, the overarching outcome will be to determine 
whether it is efficacious and beneficial to complete a longitudinal hydrotherapy intervention in 
young males with DMD, which will inform future guidelines on activity within this population. To 
this end we will conduct qualitative interviews and work alongside the members of the 
Northwest Neuromuscular network, and the Neuromuscular Centre (Winsford, UK) who 
regularly undertake hydrotherapy to engage with service users with DMD to provide guidelines 
for physical activity based on our previous work on sedentary behaviour (Jacques et al., 2018) 
and the findings of this proposed project.  
 
Qualitative interviews 
Face-to-face interviews will be conducted with 20 participants from the study. This will include a 
mixture of those with DMD, and their parents, to understand what barriers are faced when 
undertaking hydrotherapy, what about the hydrotherapy intervention was suitable, and whether 
there are benefits to hydrotherapy not captured in our outcome measures (Bagley et al., 2016). 
The interviews will be approached from an interpretivist perspective to make sense of the lived 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
experiences of those involved in the hydrotherapy (Schwartz-Shea and Yanow, 2013), 
consistent with the expertise within our research team. In addition to a scientific publication, 
these qualitative findings will inform the development of future guidelines on hydrotherapy and 
allow us to optimise participant benefit through relevant research.  
 
 
Rationale and Significance of Study: 
Protocol design justification 
While natural history studies indicate an overall negative trend in the abilities of patients 
with DMD, there is great variability in age and speed of deterioration (Muntoni et al., 2019). 
As such it is difficult to find matched controls for a short randomised intervention study. 
Instead, due to the progressive nature of DMD and the inherent variance within a mixed 
age, and ability population (e.g. upper limb & respiratory function, genetic variation 
etc.(Ricotti et al., 2019)), the participants will act as their own controls. This single-arm, 
non-crossover design where the participant acts as his own control, although not as robust 
as randomized control exercise trials, is advocated for longitudinal interventions in 
populations such as the present one (Hecksteden et al., 2018). Indeed, this self-controlled 
approach offers some of the benefits of prospective controlled trials, allows for multiple 
treatments within the same participants, and eliminates some of the covariates of group 
comparisons which are inherent in dual arm training studies (Vohra et al., 2015). 
Specifically with treatments such as hydrotherapy, the process of randomisation leads to 
patient and parent disengagement due to not getting to undertake a treatment (Hind et al., 
2017). This self-controlled study avoids the downsides of randomisation for the participants 
and is consistent with previous exercise training studies both in non-clinical (Narici et al., 
1989), and in our own training studies in muscular dystrophy (Bostock et al., 2019).  
 
Research Design 
 
The aim of this project is to undertake 12-weeks of hydrotherapy in boys and adolescents 
with DMD, and monitor the impact on body composition, bodily pain, QoL and physical 
function. The project is broken down into 3 key stages: 
Pre-experimental stage: during this stage we will secure ethical approval, and recruit 
participants. This stage will last ~6 months due to the length of time it takes to secure NHS 
ethical approval. 
Experimental stage:  the participants will complete the experimental protocol described 
below in detail. Briefly, participants will complete TWO 12-week periods. The first will be an 
observation (control) period to use as a reference point for the second period, which will 
involve 12-weeks of hydrotherapy. Figure 1 attached describes the testing sessions; these 
will be completed at 3 time points, the first before the control period, the second after the 
control period, and the third after the hydrotherapy period. The experimental stage will last 
28-months due to the staggered recruitment and testing of participants. 
Post experimental stage: this stage will involve the analysis of data and production of 
academic papers for submission within international journals. This stage will be scheduled 
for 4-months but will continue until the data has been published. Although the cost of a 
dissemination event is not formally included within this bid; as researchers and clinicians 
we regularly update physiotherapists, carers, clinicians and those with DMD through 
dissemination events. We plan to present our findings at events hosted through the 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
Northwest 
Neuromuscular 
Network, 
The 
Neuromuscular 
Centre 
outreach 
and 
dissemination days, and through the hospice website.  
Experimental stage protocol 
Participants will complete two 12-week periods, including an initial control period (CTRL), 
where they will undertake their habitual physical activity behaviour. This will be followed by 
12-weeks of hydrotherapy, where participants will complete up to 60 mins of hydrotherapy 
once a week. During these CTRL and hydrotherapy periods, diet and physical activity will 
be monitored to identify any lifestyle covariates that could contribute to their body 
composition and physical and mental wellbeing. Pre and Post CTRL, and Post 
hydrotherapy, participant outcome measures will be re-assessed. 
Consent: consent will be obtained from patients 16 years and older or parents / guardians 
of children younger then 16 years of age, either face to face or via a pre-arranged video link 
with a member of the research team who is signed off the delegation log as being able to 
take consent.  
If consent is taking place face to face, a suitable time will be arranged between a member 
of the research team and the family.  Consent can take place during the patient’s usual 
Neuromuscular clinic or at an independent appointment at the Clinical Research Facility 
(CRF). This is also a good opportunity for the young person to familiarise themselves with 
the CRF. 
If consent is taking place via a pre-arranged video link, a suitable time will be arranged 
between patient/parents/guardians and a member of the research team.  Microsoft Teams, 
Attend Anywhere or Zoom are acceptable platforms that can be used depending on 
individual Trust guidelines.  A copy of the PIS and the appropriate consent form (with all 
details completed by Research Team as needed) will be posted to the family with a pre-
paid return envelope.   
During the consent appointment, either face to face or via video link: 
1. A member of the research team will confirm they have received the PIS, have read it and 
have understood it.  
2. Patient/ Parents / guardians will be asked if they have any questions.  
3. Questions will be answered until they are content.  
4. The research team member taking consent will re-confirm the fact that the child can be 
withdrawn at any time without giving any reasons and that this will not affect the 
physiotherapy treatment the child receives.  
5. The patient/parents/guardians will then be given the consent forms. They will be asked to 
read every statement, initial each box, and sign and date at the end of the form.  
6. The research team member taking consent will then sign and date the form.  If 
appointment is completed via video link, the wet ink copy is posted back to the research 
team to sign and date and note that the form was completed by parents during the video 
link.  
7. The wet ink copy will be kept by the research team member.   

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
8. A copy of the signed consent will be given to the patient/ parents / guardian to keep for 
their own records.  If via video link, this copy will be posted to parents or given when the 
family attend for their initial assessment. 
Participants and power calculation 
We are adopting an inclusive approach to participant recruitment, which is possible through 
the within group design of the control and hydrotherapy interventions. To this end, we aim 
to recruit 44 male participants aged over 6 years of age, who have previously been 
diagnosed with DMD from multiple neuromuscular centres in the Northwest Neuromuscular 
Network (Royal Preston, Manchester, Alder Hey, Oswestry) and from Derian House 
Children’s Hospice (Chorley, UK). Participants will be included if they are able to undertake 
a single bout of hydrotherapy lasting at least 45 minutes, and are not currently ventilated 
during the day. An initial assessment will be performed by the clinical physiotherapist 
associated with the project (See attached Figure 2-Gant Chart). Exclusion criteria will 
include any regular hydrotherapy exercise within the preceding 12 weeks. 
There are at present limited data on the effect of hydrotherapy on QoL in DMD from which 
to base a power analysis, therefore we have carried out our analysis using a previous 
hydrotherapy intervention in adults with Osteoarthritis (Fransen et al., 2007). It should be 
noted that their pre intervention QoL scores were similar to those we have collected in 
DMD participants [DMD =  34.3(5.9), Osteoarthritis = 31.9 (8.5), (Means(SD))]. 
Within their 24 sessions of hydrotherapy, Fransen et al (2007) report effect sizes above that 
of control of 4.0, with no change in their control group. If we make the assumption that 
within our 12 session intervention we are likely to see half of the improvement in QoL, we 
shall base our power analysis of an effect size of 2 compared to that of controls. With the 
following values, within participant apriori power calculation performed using G*Power 
(Version 3.1.7, University of Kiel, Germany) suggests a total group number of n = 8 (α err 
prob=0.05, Power 0.95). We feel this is too conservative given that we also need to a) 
account for drop-out of participants and b) fulfil the criteria for paramatricity in a clinical 
condition that has a wide variance (children and adults with DMD ranging from 6-25 yrs are 
vary varied in the presentation of physical function). Therefore, given the aforementioned 
considerations and as this is a novel intervention in terms of research outcomes and will 
serve as a primary point of reference for subsequent hydrotherapy studies within DMD, we 
will recruit 44 participants in total.(See also table 1, summarising published hydrotherapy 
trials in similar medical conditions) 
Participants will be recruited through the respective neuromuscular clinic and through 
Derian House hospice.  
Inclusion criteria 
• 
Established diagnosis of Duchenne Muscular Dystrophy (either by genetics or 
muscle biopsy) 
• 
Between 6 and 25 years of age 
• 
On stable dose of steroids or not on steroids 
 
Exclusion criteria 
• 
Younger than 6 years, older than 25 years 
• 
Recent change in steroid dose, less than 3 months prior 
• 
Undertaking formal hydrotherapy supervised by physiotherapist on a regular basis 
(weekly or more frequent) 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
 
Body composition 
Fat mass, body fat percentage and fat free mass will be measured using bioelectrical 
impedance (BIA). Although more stringent measures of body composition exist such as 
dual-energy X-ray absorptiometry (DEXA), BIA has been validated in DMD and is accurate 
enough to measure longitudinal changes in body composition and muscle mass in this 
population (Mok et al., 2010; Kuru et al., 2019).  
Physical function  
Established physical function assessments for individuals with neuromuscular conditions 
will be completed. These will include the North-Star and Performance of the Upper Limb 
assessment (Mayhew et al., 2013); and an assessment of activities of daily living (Wu et 
al., 2011).     
Limited ankle range of motion (ROM) has long been recognised as a characteristic of 
children with DMD (Archibald and Vignos, 1959). Hydrotherapy has proven successful to 
offset impairments in children with ankle contractures albeit with Cerebral palsy (Kesiktas et 
al., 2004); ankle plantarflexion-dorsiflexion (PF-DF ROM) will be assessed through a 
goniometer.  
Grip and pinch strength will also be assessed using digital, handheld dynamometers. 
Pulmonary function 
Participants will complete lung function measures using digital spirometry. 
Mental wellbeing, QoL and pain 
The PedsQL QoL questionnaire will be used to assess QoL, as it is a reliable measure of 
disease-specific health-related QoL in those with DMD from childhood to 18 yrs of age 
(Davis et al., 2010). In addition we will use the PedsQL multidimensional fatigue scale. We 
will also use the DMD-QoL and DMD-Qol Proxy, a recently developed tool to measure 
quality of life in patients with DMD. In addition, a pain map assessment of the topographic 
distribution of daily pain will also be competed, consistent with our previous work in DMD 
(Jacques, Stockley, Bostock, et al., 2019). We will also include a participation measure 
(CASP) 
Physical activity and diet  
Triaxial accelerometers will aim to be worn for up to 7-days during the first week of CTRL 
and hydrotherapy. We have previously adopted this approach in adults with MD, and have 
reported meaningful associations between habitual PA and both QoL and ADL (Jacques et 
al., 2018). 
Over 7-days during both CTRL and hydrotherapy periods, participants will record daily food 
intake for 3 days using a smartphone app. Subsequent analysis will be performed using 
dietary analysis software (Nutritics). 
Intervention 
During the 12-week hydrotherapy intervention, participants will complete a weekly 
hydrotherapy session lasting from 30 to 60 mins. This is a duration and frequency of 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
hydrotherapy consistent with previous studies that have shown improvements in QoL in 
fibromyalgia (Mannerkorpi et al., 2002), physical function in Parkinson’s disease and 
multiple sclerosis (Salem et al., 2011; Vivas et al., 2011), and functional independence and 
mental health in adolescents with cerebral palsy (Dorval et al., 1996). An overview of 
previous studies and hydrotherapy parameters is provided in Table 1. 
The exercises, intensity and specific hydrotherapy session plan will be derived from 
consultation between the participants, and clinical physiotherapist. Due to the variance 
within the presentation of the condition and the inclusive age range within the study, we will 
take what we consider as an externally valid approach to exercise prescription. We will 
record heart rate during a sample of the participants’ hydrotherapy sessions, which will be 
included as a co-variate for subsequent analysis. 
Hydrotherapy will be conducted at Derian House Children’s Hospice (Chorley, UK), and 
may include weight-bearing activities such as standing and gait practice, assisted and 
resisted limb exercises. Core and trunk work including swimming. 
Please find attached 
Figure 1-experimental overview 
Figure 2-GANTT chart 
Figure 3- proposed experimental workflow 
Table 1 -current research in hydrotherapy 
 
 
 
Data Analysis: 
All participants will be assessed using a repeated measures design.  Given the broad 
heterogeneity of DMD participants recruited there is no meaningful benefit of intergroup 
comparisons between those participants who can complete 30-60 mins of active hydrotherapy, 
compared to those who can perform arm only, or passive hydrotherapy. Experimentally it is not 
of interest if one group changes more than another, it is of interest if there is a change within 
the individuals themselves. We have recently completed a resistance training protocol in adults 
with MD and adopted a similar approach (Bostock et al., 2019).  
 
Participants will be assessed against previous time points (Pre-CTRL vs Post-CTRL vs 
Post hydrotherapy) using repeated measures Anova (where outcomes are parametric) or 
Friedman’s (where parametric assumptions are violated). Tests of association will be used 
to compare relative hydrotherapy intensity with changes from PRE to Post hydrotherapy. 
 
Adverse Events: 
All adverse events will be reported to the Chief Investigator and study Sponsor. 
Depending on the nature of the event the reporting procedures below will be 
followed. Any questions concerning adverse event reporting will be directed to the 
Chief Investigator in the first instance. 
  
Adverse Events 
  
If an incident needs acute attention, a member of the research team will follow local 
emergency procedures. 
These will be recorded using the Adverse Event Reporting form, discussed with CI 
and paediatricians/ physiotherapist of team and escalated to the study Sponsor. 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
  
Serious Adverse Events 
  
No SAE is anticipated, however, in the event of a suspected SAE occurring a form 
will be completed by a member of the research team, who will then notify (in person 
or via Egress secure email) the Chief Investigator and Sponsor 
representative within 24 hours. The Chief Investigator and Sponsor will assess and 
determine if the SAE is related to the study procedures and report back to the 
research team via e-mail. 
  
All SAEs will be reported to the ethics committee where, in the opinion of the Chief 
Investigator, the event was: 1 ‘related’, i.e. resulted from the administration of any of 
the research procedures; and 2 ‘unexpected’, i.e. an event that is not listed in the 
protocol as an expected occurrence.  Reports of related and unexpected SAEs will 
be submitted within 15 days of the Chief Investigator becoming aware of the event, 
using the SAE form for non-IMP studies. 
 
Monitoring: 
The conduct and running of this research project will be overseen by the Chief Investigator 
which may be delegated to lead research physiotherapist. They will 
audit and monitor the research through all the stages and until completion on a risk 
assessed basis. The audit and monitoring process will be conducted in line with the terms 
of funding for the research and in line with LTHTR's policies, procedures, and the Research 
Governance Framework. 
  
Local teams will also be answerable to their local R&D department, who will also monitor 
and audit all research undertaken at the Trust. 
 
Dissemination: 
The results of this study will be used to inform the neuromuscular service in Preston and 
at other sites in the UK. The results will also be shared more widely by presenting them 
at regional and or national meetings. The results may be published in a scientific journal 
and presented at scientific medical conferences and through publications and meetings 
organised by Duchenne UK. Outcomes will also be shared by DMD Care UK to help 
improve the standards of care. You will not be identified in any report or publication. 
 
Ethical issues: 
 
Ethical review and approval will be sought through an application through IRAS. (Reference 
304633) 
 
 
References: 
Archibald, K. and Vignos, P. (1959) 'A study of contractures in muscular dystrophy.' 
Arch Phys Med Rehabil, 40(4) pp. 150-157. 
 
Bagley, H. J., Short, H., Harman, N. L., Hickey, H. R., Gamble, C. L., Woolfall, K., 
Young, B. and Williamson, P. R. (2016) 'A patient and public involvement (PPI) 
toolkit for meaningful and flexible involvement in clinical trials–a work in progress.' 
Research involvement and engagement, 2(1) p. 15. 
 
Birnkrant, D. J., Bushby, K., Bann, C. M., Apkon, S. D., Blackwell, A., Brumbaugh, 
D., Case, L. E., Clemens, P. R., Hadjiyannakis, S. and Pandya, S. (2018) 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
'Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, 
and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional 
management.' The Lancet Neurology, 17(3) pp. 251-267. 
 
Bostock, E. L., Edwards, B. T., Jacques, M. F., Pogson, J. T., Reeves, N. D., Onambele-
Pearson, G. L. and Morse, C. I. (2018) 'Impaired Glucose Tolerance in Adults with 
Duchenne and Becker Muscular Dystrophy.' Nutrients, 10(12) p. 1947. 
 
Bostock, E. L., O'Dowd, D. N., Payton, C. J., Smith, D., Orme, P., Edwards, B. T. and Morse, 
C. I. (2019) 'The Effects of Resistance Exercise Training on Strength and Functional 
Tasks in adults with Limb-Girdle, Becker and Facioscapulohumeral Dystrophies.' 
Frontiers in Neurology, 10 p. 1216. 
 
Bushby, K., Bourke, J., Bullock, R., Eagle, M., Gibson, M. and Quinby, J. (2005) 'The 
multidisciplinary management of Duchenne muscular dystrophy.' Current Paediatrics, 
15(4) pp. 292-300. 
 
Cunha, M. C., Oliveira, A. S., Labronici, R. H. D. and Gabbai, A. A. (1996) 'Spinal muscular 
atrophy type II (intermediary) and III (Kugelberg-Welander): evolution of 50 patients 
with physiotherapy and hydrotherapy in a swimming pool.' Arquivos de neuro-
psiquiatria, 54(3) pp. 402-406. 
 
Davis, S. E., Hynan, L. S., Limbers, C. A., Andersen, C. M., Greene, M. C., Varni, J. W. and 
Iannaccone, S. T. (2010) 'The PedsQL™ in pediatric patients with duchenne muscular 
dystrophy: feasibility, reliability, and validity of the pediatric quality of life inventory 
neuromuscular module and generic core scales.' Journal of clinical neuromuscular 
disease, 11(3) pp. 97-109. 
 
de Mattos, F., Leite, N., Pitta, A. and Bento, P. C. B. (2016) 'Effects of aquatic exercise on 
muscle strength and functional performance of individuals with osteoarthritis: a 
systematic review.' Revista Brasileira de Reumatologia (English Edition),  
 
Dorval, G., Tetreault, S. and Caron, C. (1996) 'Impact of aquatic programmes on 
adolescents with cerebral palsy.' Occupational Therapy International, 3(4) pp. 241-261. 
 
Fransen, M., Nairn, L., Winstanley, J., Lam, P. and Edmonds, J. (2007) 'Physical activity 
for osteoarthritis management: a randomized controlled clinical trial evaluating 
hydrotherapy or Tai Chi classes.' Arthritis Care & Research, 57(3) pp. 407-414. 
 
Hecksteden, A., Faude, O., Meyer, T. and Donath, L. (2018) 'How to construct, conduct 
and analyze an exercise training study?' Frontiers in Physiology, 9 
 
Hind, D., Parkin, J., Whitworth, V., Rex, S., Young, T., Hampson, L., Sheehan, J., Maguire, 
C., Cantrill, H. and Scott, E. (2017) 'Aquatic therapy for boys with Duchenne muscular 
dystrophy (DMD): an external pilot randomised controlled trial.' Pilot and Feasibility 
Studies, 3(1) p. 16. 
 
Honório, S. (2011) AQUATIC INFLUENCE ON MOBILITY OF A CHILD WITH DUCHENNE 
MUSCULAR DYSTROPHY: CASE STUDY. Instituto Politécnico de Castelo Branco, 
Portugal. 
 
Honório, S., Batista, M. and Martins, J. (2013) 'The influence of hydrotherapy on obesity 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
prevention in individuals with Duchenne Muscular Dystrophy.' Journal of Physical 
Education and Sport, 13(2) p. 140. 
 
Hunt, A., Carter, B., Abbott, J., Parker, A. and Spinty, S. (2016) 'Pain experience, 
expression and coping in boys and young men with Duchenne Muscular Dystrophy–A 
pilot study using mixed methods.' European Journal of Paediatric Neurology, 20(4) pp. 
630-638. 
 
Jacques, M. F., Onambele‐Pearson, G. L., Reeves, N. D., Stebbings, G. K., Smith, J. and 
Morse, C. I. (2018) 'Relationships between muscle size, strength, and physical activity 
in adults with muscular dystrophy.' Journal of cachexia, sarcopenia and muscle, 9(6) pp. 
1042-1052. 
 
Jacques, M. F., Stockley, R. C., Bostock, E. I., Smith, J., DeGoede, C. G. and Morse, C. I. 
(2019) 'Frequency of reported pain in adult males with muscular dystrophy.' PLoS One, 
14(2) p. e0212437. 
 
Jacques, M. F., Stockley, R. C., Onambele-Pearson, G. L., Reeves, N. D., Stebbings, G. K., 
Dawson, E. A., Groves, L. and Morse, C. I. (2019) 'Quality of life in adults with muscular 
dystrophy.' Health and quality of life outcomes, 17(1) p. 121. 
 
Jansen, M., van Alfen, N., Geurts, A. C. and de Groot, I. J. (2013) 'Assisted bicycle training 
delays functional deterioration in boys with Duchenne muscular dystrophy: the 
randomized controlled trial “no use is disuse”.' Neurorehabilitation and neural repair, 
27(9) pp. 816-827. 
 
Karjalainen, K. A., Malmivaara, A., van Tulder, M. W., Roine, R., Jauhiainen, M., Hurri, H. 
and Koes, B. W. (1999) 'Multidisciplinary rehabilitation for fibromyalgia and 
musculoskeletal pain in working age adults.' The Cochrane Library,  
 
Kesiktas, N., Paker, N., Erdogan, N., Gülsen, G., Bicki, D. and Yilmaz, H. (2004) 'The use 
of hydrotherapy for the management of spasticity.' Neurorehabilitation and neural 
repair, 18(4) pp. 268-273. 
 
Kohler, M., Clarenbach, C. F., Böni, L., Brack, T., Russi, E. W. and Bloch, K. E. (2005) 
'Quality of life, physical disability, and respiratory impairment in Duchenne muscular 
dystrophy.' American journal of respiratory and critical care medicine, 172(8) pp. 1032-
1036. 
 
Kuru, S., Uchiyama, T., Hattori, A., Sato, T., Murakami, T., Ishigaki, K. and Nakayama, T. 
(2019) 'Assessment of muscle involvement in patients with Duchenne muscular 
dystrophy via segmental multifrequency bioelectrical analysis.' Neuromuscular 
Disorders, 29(9) pp. 671-677. 
 
Mannerkorpi, K., Ahlmén, M. and Ekdahl, C. (2002) 'Six-and 24-month follow-up of pool 
exercise therapy and education for patients with fibromyalgia.' Scandinavian journal of 
rheumatology, 31(5) pp. 306-310. 
 
Marinho-Buzelli, A. R., Bonnyman, A. M. and Verrier, M. C. (2014) 'The effects of aquatic 
therapy on mobility of individuals with neurological diseases: a systematic review.' 
Clinical rehabilitation,  p. 0269215514556297. 
 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
Mayhew, A., Mazzone, E. S., Eagle, M., Duong, T., Ash, M., Decostre, V., Vandenhauwe, M., 
Klingels, K., Florence, J. and Main, M. (2013) 'Development of the Performance of the 
Upper Limb module for Duchenne muscular dystrophy.' Developmental Medicine & 
Child Neurology, 55(11) pp. 1038-1045. 
 
Mayo, A., Craven, B., McAdam, L. and Biggar, W. (2012) 'Bone health in boys with 
Duchenne muscular dystrophy on long-term daily deflazacort therapy.' Neuromuscular 
Disorders, 22(12) pp. 1040-1045. 
 
McDonald, C. M., Widman, L. M., Walsh, D. D., Walsh, S. A. and Abresch, R. T. (2005) 'Use 
of step activity monitoring for continuous physical activity assessment in boys with 
Duchenne muscular dystrophy.' Arch Phys Med Rehabil, 86(4) pp. 802-808. 
 
Mok, E., Letellier, G., Cuisset, J.-M., Denjean, A., Gottrand, F. and Hankard, R. (2010) 
'Assessing change in body composition in children with Duchenne muscular 
dystrophy: anthropometry and bioelectrical impedance analysis versus dual-energy X-
ray absorptiometry.' Clinical nutrition, 29(5) pp. 633-638. 
 
Morse, C. I., Bostock, E. L., Twiss, H. M., Kapp, L. H., Orme, P. and Jacques, M. F. (2018) 
'The cardiorespiratory response and physiological determinants of the assisted 
6‐minute handbike cycle test in adult males with muscular dystrophy.' Muscle Nerve,  
 
Muntoni, F., Domingos, J., Manzur, A. Y., Mayhew, A., Guglieri, M., Network, T. U. N., 
Sajeev, G., Signorovitch, J. and Ward, S. J. (2019) 'Categorising trajectories and 
individual item changes of the North Star Ambulatory Assessment in patients with 
Duchenne muscular dystrophy.' PLoS One, 14(9) 
 
Narici, M. V., Roi, G., Landoni, L., Minetti, A. and Cerretelli, P. (1989) 'Changes in force, 
cross-sectional area and neural activation during strength training and detraining of 
the human quadriceps.' Eur J Appl Physiol Occup Physiol, 59(4) pp. 310-319. 
 
Ricotti, V., Selby, V., Ridout, D., Domingos, J., Decostre, V., Mayhew, A., Eagle, M., Butler, 
J., Guglieri, M. and Van der Holst, M. (2019) 'Respiratory and upper limb function as 
outcome measures in ambulant and non-ambulant subjects with Duchenne muscular 
dystrophy: A prospective multicentre study.' Neuromuscular Disorders, 29(4) pp. 261-
268. 
 
Ryan, D., Wullems, J., Stebbings, G., Morse, C., Stewart, C. and Onambele-Pearson, G. 
(2018) 'Segregating the Distinct Effects of Sedentary Behavior and Physical Activity on 
Older Adults’ Cardiovascular Structure and Function: Part 1—Linear Regression 
Analysis Approach.' Journal of Physical Activity and Health, 20(XX) pp. 1-11. 
 
Salem, Y., Scott, A. H., Karpatkin, H., Concert, G., Haller, L., Kaminsky, E., Weisbrot, R. 
and Spatz, E. (2011) 'Community-based group aquatic programme for individuals with 
multiple sclerosis: a pilot study.' Disabil Rehabil, 33(9) pp. 720-728. 
 
Schwartz-Shea, P. and Yanow, D. (2013) Interpretive research design: Concepts and 
processes. Routledge. 
 
Steele, M., Taylor, E., Young, C., McGrath, P., Lyttle, B. D. and Davidson, B. (2008) 
'Mental health of children and adolescents with Duchenne muscular dystrophy.' 
Developmental Medicine & Child Neurology, 50(8) pp. 638-639. 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
 
UK, M. D. (2015) Hydrotherapy in the UK: The urgent need for increased access. UK.  
 
Vivas, J., Arias, P. and Cudeiro, J. (2011) 'Aquatic therapy versus conventional land-
based therapy for Parkinson's disease: an open-label pilot study.' Arch Phys Med 
Rehabil, 92(8) pp. 1202-1210. 
 
Vohra, S., Shamseer, L., Sampson, M., Bukutu, C., Schmid, C. H., Tate, R., Nikles, J., Zucker, 
D. R., Kravitz, R. and Guyatt, G. (2015) 'CONSORT extension for reporting N-of-1 trials 
(CENT) 2015 Statement.' Bmj, 350 p. h1738. 
 
Winter, Y., Schepelmann, K., Spottke, A. E., Claus, D., Grothe, C., Schröder, R., Heuss, D., 
Vielhaber, S., Tackenberg, B. and Mylius, V. (2010) 'Health-related quality of life in ALS, 
myasthenia gravis and facioscapulohumeral muscular dystrophy.' Journal of neurology, 
257(9) pp. 1473-1481. 
 
Wu, C.-y., Chuang, L.-l., Lin, K.-c. and Hong, W.-h. (2011) 'Responsiveness, minimal 
detectable change, and minimal clinically important difference of the Nottingham 
Extended Activities of Daily Living Scale in patients with improved performance after 
stroke rehabilitation.' Arch Phys Med Rehabil, 92(8) pp. 1281-1287. 
 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
 
 
 
 
 
 
 
 
 
 
 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
 
 
 
 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23 
 
 
 

 
 
IRAS No. 304633 
 
Protocol, v.3, Date: 22/08/23