Yoga Outcomes Get Assessed in Cystic Fibrosis (YOGA-CF): protocol of a multicentre interventional randomised controlled clinical trial—investigating effects of a 12-week yoga intervention for adults with cystic fibrosis

Abstract

Introduction

Yoga is an emerging exercise choice for people with cystic fibrosis (CF), but evidence of its effect in this population is scarce, with a recent systematic review advocating for further research. Yoga Outcomes Get Assessed in CF (YOGA-CF) is a real-world multicentre randomised controlled trial (RCT) investigating a bespoke CF-specific online 12-week yoga intervention, vers usual care, to determine effectiveness for adults with CF.

Methods and analysis

A multicentre RCT of adults with CF across the UK. Participants are randomised to usual care or a 12-week online bespoke yoga programme with an expectation of two classes completed weekly. Assessments of lung function, 1 min sit-to-stand, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and other trial questionnaires are completed preintervention and postintervention (0 and 12 weeks) and after 12 weeks of follow-up (week 24). The primary outcome is the difference in respiratory-related quality of life measured using the CFQ-R before and after yoga/control. Sample size was calculated based on detecting a minimally clinically important difference of 4 for the CFQ-R respiratory domain, with power of 80% and 5% significance level (total target, n=314).

Ethics and dissemination

Ethics approval gained from the South Yorkshire and Humber Research Ethics Committee (REC) (reference: 23/YH/0270, project ID 303898). Dissemination to involve direct participant feedback and lay webinar, scientific conference presentation and publication in a peer-reviewed journal.

Trial registration number

NCT06120465.

WHAT IS ALREADY KNOWN ON THIS TOPIC.

WHAT THIS STUDY ADDS

• This is the first large-scale statistically powered multicentre randomised controlled trial to investigate the effects of a bespoke yoga intervention tailored for adults with CF.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• This study will inform the CF community, clinical practice and service providers about effects of yoga practice for adults with CF. Yoga Outcomes Get Assessed in CF will influence future research into exercise and yoga interventions for adults and children with CF.

Introduction

As of 2023, over 11 300 people in the UK have cystic fibrosis (CF),¹ a life-limiting multisystem genetic disease. While life expectancy is improving, the current median age of death remains low (46 years¹), with the main cause of death being respiratory failure.¹ While there is no cure, current management strategies help people with CF (pwCF) live longer and fuller lives. Strategies include cystic fibrosis transmembrane conductance regulator (CFTR) modulator medications to correct the basic CF protein defect; airway clearance and antibiotics to prevent respiratory infections; nutritional repletion; and physical activity.

Physical activity and exercise have been shown to have beneficial effects on fitness levels, physical function, muscles, bone structure, posture, quality of life and complement airway clearance techniques (ACTs), helping to keep the chest clear.^{2 3} With the introduction of CFTR modulator medications, it is hoped that pwCF will have greater opportunities to participate in physical activity as part of a healthy lifestyle.

Yoga, an ancient body–mind practice combining breathing exercises (called pranayama), relaxation or mindfulness techniques with physical postures (called asanas), is an emerging field in CF, specifically as a non-pharmacological option for health management. A survey of UK CF centres reported perceived benefits of improvements to back pain, airway clearance, body image, disease mastery, breath awareness, sleep, anxiety and cardiovascular fitness.² With increasing life expectancy and improvements in disease stability, especially for individuals established on CFTR modulator medications, holistic management strategies with multiple potential beneficial effects, such as yoga, may be an optimal way to reduce treatment burden while maintaining health.

However, despite interest in yoga from the CF community, research evidence of its effectiveness in this population is limited to small population studies. Yoga has been reported as safe and well tolerated by pwCF^{4 5} with suggested improvements in anxiety,⁵ joint pain,⁵ chest wall excursion,⁶ lower extremity muscle performance⁶ and respiratory-related quality of life.⁴

Results from studies in the general population indicate that yoga improves muscle strength and body flexibility; promotes and improves respiratory and cardiovascular function; reduces stress, anxiety, depression and chronic pain; improves sleep patterns and enhances overall well-being and quality of life.⁷ A 2020 survey of 2434 yoga practitioners noted the value of yoga for many health conditions, but especially mental health and musculoskeletal (MSK) issues.⁸ Larger-scale research studies in other respiratory conditions have shown beneficial effects.⁹ In asthma, a 6- week yoga programme improved quality of life and lung function for participants,¹⁰ while in chronic obstructive pulmonary disease, functional improvements were reported.¹¹

A 2014 systematic review into meditative movement, including yoga, concluded there is as yet insufficient evidence to support meditative movement for pwCF and advocated completion of well powered, randomised controlled studies of meditative movement.¹² This study seeks to address this evidence gap by investigating effects of yoga for a large sample of adults with CF within a robust randomised clinical trial design.

We hypothesise that yoga will have beneficial effects on respiratory health-related quality of life (HRQoL), measured by the Cystic Fibrosis Questionnaire-Revised (CFQ-R)^{13 14} respiratory domain, for adults with CF. Additional effects to be investigated include reported pain, lung function, exercise participation and physical function. We will also complete an economic evaluation to assess the cost-effectiveness of yoga practice from the perspective of the National Health Service (NHS) and social services.

Methods and analysis

Trial registration and funding

This trial is registered on the public database www.clinicaltrials.gov.uk (reference NCT06120465). It is funded by a Vertex Pharmaceuticals Innovation Award (reference Yoga Outcomes Get Assessed in CF (YOGA-CF)).

Patient involvement

Patients were involved in the conceptualisation, design, conduct and dissemination plan of this research. During planning, patient opinions on the trial design, research question, trial burden and recruitment methods were gathered via discussions with adults with CF, and through focus group work aided by the Cystic Fibrosis Trust, UK.¹⁵ Study assessment questionnaires (see online supplemental appendix 1), recruitment and dissemination strategies were designed and developed in conjunction with two patient representatives involved as part of the YOGA-CF trial management team. A further patient representative is also an independent member of the trial steering committee.

Study design

An open-label, multicentre, interventional randomised controlled clinical trial investigating the effects of a 12-week yoga programme delivered via an online platform (Beam) in adults with CF. Figure 1 illustrates the study design.

Figure 1. Yoga Outcomes Get Assessed in Cystic Fibrosis study design.

Recruitment

Adults (16 years and older) with CF registered at one of the participating UK CF centres are eligible. To optimise recruitment and generalisability of results, trial participation will be open to all adult CF centres across the UK; further, we have kept inclusion/exclusion criteria as broad as practicable—while maintaining safety—to promote inclusiveness. Wifi data bundles or dongles will be provided to participants requiring support to access the assessments and online programme to reduce digital or financial barriers to participation.

Patients are approached during routine clinic visits or via email/telephone for a project introduction and given a patient information sheet (PIS). They are given at least 48 hours to consider the PIS before follow-up communication is completed, to discuss questions regarding study involvement and arrange their baseline study assessment visit if applicable.

Each yoga class will have a maximum of 15 participants to allow group interaction and instructor feedback. Participants will be given a choice of four different classes running on different days and times. Consequently, each 12-week programme can accommodate a maximum of 60 people, requiring at least five consecutive deliveries to complete recruitment. To minimise the duration of data collection, recruitment for each set (‘block’) of the 12-week programme for blocks 2–6 took place as the preceding block moved to completion, as depicted in figure 2.

Figure 2. Yoga Outcomes Get Assessed in Cystic Fibrosis recruitment.

Inclusion/exclusion criteria

Table 1 lists study inclusion and exclusion criteria. Discontinuation criteria include self-determined withdrawal by participants; pregnancy awareness during study; and clinical deterioration during participation that makes yoga practice unsafe, as determined by either the CF medical team responsible for the participant’s care or by the research team.

Table 1. Inclusion and exclusion criteria.

Inclusion criteria	Exclusion criteria
Diagnosis of CF (confirmed by standard criteria; Farrell et al 2017)39	Inability to provide consent to participate in the trial
Sixteen years of age or over	Current participation in another interventional study of a medicinal product
Access to an electronic device which can access the internet	Current moderate haemoptysis (greater than streaking in the sputum)
Ability to complete questionnaires in English	Use of ambulatory oxygen therapy, long-term oxygen therapy or non-invasive ventilation
Stable CF disease as judged by the local PI, in conjunction with the CF clinical team	Known pregnancy at the time of recruitment
Registered as a patient of one of the participating CF centres	Forced expiratory volume in 1 s below 30% predicted at baseline (taken within 1 year of recruitment)
	Current regular participation in yoga practice
	Current neurological or musculoskeletal injury which would prevent completion of yoga
	Diagnosis of osteoporosis (bone density Z score <−2.5) or history of spontaneous spinal fractures
	Uncontrolled gastro-oesophageal reflux
	Pulmonary exacerbation within 28 days of screening
	Lung transplant recipient

CF, cystic fibrosis.

Informed consent

A PIS is distributed to each identified potential participant with verbal study explanation and the opportunity to ask questions at the first recruitment contact. A further study overview is given at the week zero contact and participants can ask questions before consenting. Electronic written consent is collected using the YOGA-CF Research Electronic Data Capture (REDCap) database^{16 17} at the week zero contact, and consent is verbally reconfirmed at contacts in weeks 12 and 24.

Interventions

Subjects will be randomly assigned to either control or the yoga intervention.

The control group continues their usual CF management as instructed by their CF medical team, completing study assessments at baseline and weeks 12 and 24.

The intervention group completes baseline assessments and then completes the online yoga programme through the YOGA-CF BEAM webpage. The yoga course is a 12-week progressive programme, with a different theme each week (with two classes on each theme) (see online supplemental material). All classes have been recorded and are available on-demand and are also supported by live online classes where participants can receive feedback from the instructor. Live classes will be offered at a variety of times and days with participants encouraged to attend at least one live class per week. Yoga participants are free to turn their camera off during live classes, enabling them to choose privacy should they wish. Live yoga classes will last 45 min, while prerecorded classes will last 30 min. Expected engagement for the intervention group will be one live class and one prerecorded yoga class per week. All participants continue with usual CF management, including medications and ACT routines. The number of live and pre-recorded sessions completed will be recorded as a marker of programme adherence.

End of trial and follow-up

Both groups have follow-up assessments at 24 weeks. Subsequently, control group participants will be offered off-protocol access to 12 weeks of yoga classes via the BEAM platform.

The trial ends when the sample has been recruited and each participant’s 24-week assessment window has completed. Follow-up emails and telephone calls will be completed for participants who fail to complete week 12 and week 24 assessments to promote participant retention and follow-up data completion.

Randomisation and blinding

Treatment allocation will be random and in a 1:1 ratio between study groups. The random allocation sequence will be computer-generated (specified by the trial statistician) and will use varying permuted block sizes and be stratified by sex. There will be separate randomisation lists for each centre for each 12-week yoga block. Randomisation lists will be created by the trial statistician (who is not involved in trial interventions or assessments) and uploaded onto the REDCap database. After consent, local centre principal investigators will automatically be shown the randomisation outcome of their participant through the REDCap database.

Given the nature of the intervention, this trial is not blinded for participants or investigators.

To minimise performance bias, all participants will receive standardised instructions and support for trial assessments regardless of group allocation. Trial questionnaires (including primary endpoint (CFQ-R)) will be completed by participants independently from the research team, after being delivered via a centralised point with standard instructions. Trial assessments of spirometry and 1 min sit-to-stand test will be completed based on standardised instructions. All trial sites will be trained on delivering trial visits to promote consistency across participants and sites.

Non-specific factors such as contact time with the research team, setting and general encouragement will be applied as consistently as possible between groups seeking to minimise confounders between arms, placebo effects and differential expectations.

To minimise detection bias, most primary and secondary outcomes will be evaluated using validated, standardised assessment tools administered in a uniform manner across both study arms. Where non-validated outcomes are used (eg, trial-specific questionnaires), standardised instructions will be used in a uniform manner across both groups. With self-reported measures, respondents will be reminded to answer independently; further, responses will be collected electronically, maintaining confidentiality and helping to reduce performance bias.

Study assessments

After consent and randomisation, a video appointment will be arranged to complete an assessment of the 1 min sit-to-stand test and spirometry. During this call, electronic versions of the trial questionnaires (CFQ-R; Musculoskeletal Health Questionnaire (MSK-HQ); EQ-5D-5L; health service use questionnaire; questions about exercise participation (table 2)) will be sent to participants for completion. Face-to-face assessments will be permitted if more feasible or convenient for participants.

Table 2. Schedule of trial procedures and assessments.

Study procedures	Screening	Baseline (postrandomisation)	During yoga intervention	End of trial (after 12 weeks)	End of follow-up (after 24 weeks)
Informed consent	X
Check continued informed consent		X		X	X
Inclusion/exclusion criteria	X
Medical history	X
Demographics	X
Discussion about general health	X
Measures CFQ-R Spirometry (FEV1 and FVC) MSK-HQ 1-minute sit-to-stand EQ-5D-5L Health resources use questionnaire		X		X	X
Yoga group week 12 questionnaire				X
Yoga group week 24 questionnaire					X
Control group week 24 questionnaire					X
Session effect questions			X
Questions about exercise participation		X		X	X
Recording of number of previous exacerbations for the last 24 weeks		X
Recording of number of pulmonary exacerbations of the past 12 weeks				X	X

CFQ-R, Cystic Fibrosis Questionnaire-Revised; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; MSK-HQ, Musculoskeletal Health Questionnaire.

Questions about participants’ general health will be asked before each yoga class to assess participation safety. Questions about breathing and airway clearance will be completed after each yoga class (see online supplemental material). At weeks 12 and 24, both groups repeat baseline assessments via a prearranged video appointment and online invitation to electronic versions of the questionnaires. At 12 weeks, the intervention group receives a questionnaire about their experience of yoga and perceived impacts; a similar questionnaire follows again at 24 weeks, with further questions maintaining yogic practice (see online supplemental material). Prompts to complete questionnaires will be sent electronically or through phone calls to participants if required. Table 2 depicts the schedule of assessments.

To ensure assessment while clinically stable, baseline assessments will be completed in a period of clinical stability (defined as at least 28 days from pulmonary exacerbation, as per inclusion criteria). As far as possible, all 12-week and 24-week assessments will be completed within a 2-week window.

Primary and secondary measures

Table 3 summarises study outcomes and associated measures.

Table 3. Primary and secondary outcomes.

Primary outcome	Outcome measure
Respiratory-related quality of life	Respiratory domain of the CFQ-R13 14 26
Secondary outcomes	Outcome measures
Health-related quality of life including aspects relating to physical function, emotion and gastrointestinal symptoms	Eleven other domains of the CFR-Q13 14 (physical functioning, vitality, body, weight, emotion, health, treat, role, eat, digestive, social)
Lung function	FEV1 and FVC
Airway clearance	Session effect questions (online supplemental material)
Musculoskeletal symptoms including pain, stiffness, sleep disturbance, physical function	Arthritis Research UK MSK-HQ20
Functional capacity and strength	One-Minute Sit-to-Stand Test21
Cost utility analysis	EQ-5D-5L23; health resource use questionnaire
Number of pulmonary exacerbations in the last 24 weeks	Number of new prescriptions of oral or intravenous antibiotics in the last 24 weeks

CFQ-R, Cystic Fibrosis Questionnaire-Revised; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; MSK-HQ, Musculoskeletal Health Questionnaire.

The primary outcome is respiratory-related quality of life as measured by the respiratory domain of the CFQ-R,¹⁴ distributed and completed electronically. The CFQ-R is a disease-specific HRQoL measure validated for pwCF. It is a profile measure of HRQoL with 12 different domains, with higher scores indicating better quality of life. The remaining 11 domains will be analysed as secondary endpoints.

Secondary outcomes

Spirometry

Spirometry is measured using spirometers by SpiroBank, Vitalograph or Nuvoair (hand-held spirometers commonly used clinically by pwCF), following ATS/ERS guidelines.¹⁸ Measurements will include forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) manoeuvres. Both absolute (litres) and percentage predicted values will be recorded, providing continuous data for analysis. Each test is repeated three times and the best value recorded. Percentage predicted values are obtained using the Global Lung Initiative 2021 (GLI) equations.¹⁹

Musculoskeletal Health Questionnaire

This is a MSK patient-reported outcome measure, designed to be used across the spectrum of MSK conditions.²⁰ MSK-HQ contains 14 questions answered on a 5-point scale, with higher scores indicating fewer MSK symptoms, which provides discrete numerical data for analysis.

One-minute sit-to-stand test

This test involves the participant being timed for 1 min performing sit to stand manoeuvres from the same standard height chair (height 40–45 cm) for all tests.²¹ The total number of manoeuvres performed will be recorded, providing discrete numerical data for analysis. The modified Borg scale²² will be used to assess participant exertion with participants giving values before and after the test (see online supplemental material). Heart rate and oxygen saturations will be recorded pre/post with a pulse oximeter.

EuroQol EQ-5D-5L HRQoL questionnaire

This questionnaire consists of five items asking about the person’s health on that day, with dimensions relating to pain, mobility, anxiety/depression, usual activities and self-care.²³ Each dimension has five levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Additionally, it contains a visual analogue scale asking the participant to indicate on a scale ranging 0–100 how good their health is that day (0=worst imaginable, 100=best imaginable). Responses to the first five items describe health states, will be mapped to a health utility typically ranging between 1 (‘perfect health’) and 0 (considered equivalent to death). We will use the mapping recommended at the time of analysis.²⁴ At the time of writing, current guidance recommends valuation using the method proposed in Hernández et al²⁵ whereby −5 L data are mapped onto −3 L valuation set.

Non-validated trial-specific questionnaires

Health services use questionnaire

This collects information about use of NHS services—specifically CF services—at 0, 12 and 24 weeks. Questionnaire responses will be used to inform the comparative resource use and costs between trial arms. This was developed with patient and public involvement input and informed by our other CF work.

Exercise participation questions

Participants will be asked questions about current exercise at 0, 12 and 24 weeks to ascertain exercise habits and recent routine changes. Questions will provide discrete numeric data for analysis and qualitative data for thematic analysis.

Post-yoga assessment questionnaire at 12 and 24 weeks

These questionnaires ask about likelihood of continuing yoga, ease of completing sessions, barriers to participation and perceived benefits. Likert style questions will create discrete numerical data for analysis, with some qualitative data to be analysed for themes.

Post-control assessment questionnaire at 24 weeks

This questionnaireasks about planned likelihood to complete yoga and barriers to participation. Likert style questions provide discrete numerical data for analysis with some qualitative data to be analysed for themes.

Postclass session effect questions

Two questions asking participants to rate the impact of each yoga session on breathing and sputum clearance, each rated on a five-point Likert scale providing discrete numerical data.

Data collection and storage

Study data are collected and managed using REDCap electronic data capture tools hosted at the Royal Brompton Hospital (RBH). REDCap is a secure, web-based software platform designed to support data capture for research studies.^{16 17}

Sample size calculations

Based on detecting a minimally clinically important difference (MCID) of 4 for the CFQ-R respiratory domain,²⁶ with a power of 80%, 5% significance level and assuming a SD of 12,²⁷ we require 143 people per group. To allow for a 10% drop-out, we will require 157 people per study group, giving a total sample size of 314.

Data analysis plan

Demographic and outcome numerical data will be summarised as mean (SD) or median (IQR) depending on the distribution of the data and categorical data will be presented as frequencies (percentage).

Primary outcome analysis

Primary analysis of outcome measures will follow the intention-to-treat principle.

For the primary outcome (CFQ-R respiratory domain score at 12 weeks), a mixed-effects linear regression model, with CF centre as random effect, will be used to estimate a mean difference in CFQ-R domain score between the two arms of the trial. The estimated mean difference will be adjusted for sex and yoga block and presented with a 95% CI. The p-value for treatment group obtained from the adjusted model will be presented.

Secondary outcome analysis

For secondary outcomes FEV₁, FVC, MSK-HQ EQ-5L-5D and other domains of CFQ-R at 12 weeks, estimates of mean difference and 95% CIs will be obtained from linear regression models as for the primary outcome. A linear or Poisson regression model will be used to estimate mean difference in the number of sit-to-stands in 1 min.

Changes in the responses to specific questions in the yoga feedback questionnaire between 12 and 24 weeks will be described using frequency and percentages. Within each study group, changes in responses about exercise participation will be described using frequencies and percentages. Qualitative data will be described in themes.²⁸

Economic evaluation

We will conduct a within-trial cost-utility analysis, assessing the relative cost-effectiveness of the yoga programme in addition to usual clinical care, compared with usual clinical care alone. The costing perspective will be that of the NHS and personal social services, as preferred by NICE,²⁹ focused on CF-specific resource use. Health resource use will be collected using the health services use questionnaire completed by participants (administered at baseline, 12 and 24 weeks). Cost components will comprise primary and social care consultations (eg, with a General Practitioner (GP), nurse or physiotherapist); hospital visits (eg, inpatient episodes, outpatient visits and accident and emergency admissions); prescribed treatments; and costs of the yoga intervention. Associated costs of this resource use will be determined using standard costing resources,^{30 31} using the latest cost-year for which these are available²³ valued according to latest NICE guidance at time of analysis^{32 33} to calculate quality adjusted life years using linear interpolation.³⁴ Analysis will report both unadjusted and adjusted (using regression) mean and incremental cost and outcomes per patient, and incremental cost-effectiveness ratios (ICERs); assuming one treatment option does not dominate (ie, is less costly and more effective than the other). Where an ICER is calculated, it will be considered cost-effective if it falls in, or below, the range of £20 000–30 000/QALY, the typical NICE threshold. Uncertainty will be measured using 95% CIs and cost effectiveness acceptability curves—the latter calculating the probability of cost-effectiveness at a range of willingness to pay for a QALY. We will conduct sensitivity analyses to explore the robustness of results, including³⁵ impact of approaches for addressing missing data. A detailed health economics analysis plan will be agreed on with the Trial Steering Committee before all data have been collected and analysis and reporting will conform to current best-practice guidelines.

Other analyses

We will calculate minimally important changes (MICs) of outcome measures using an anchor-based method36,38 derived from session effect questions and the postyoga week 12 questionnaire. MICs differ from minimally clinically relevant differences (MCRDs) and MCIDs, because MICs are based on patient feedback, and so represent the required change of an outcome measure for a patient to perceive a difference,³⁷ as opposed to a MCRD or MCID which are defined by clinical experts.³⁶

A subgroup sensitivity analysis excluding the top 5%, 10% and 15% responses to the CFQ-R respiratory domain from the whole cohort is planned to explore potential outcome ceiling effects. An exploratory analysis investigating the potential interaction of baseline CFQ-R scores on outcome is planned.

Interim analysis of recruitment and data completeness will be conducted on completion of the first block to ensure data collection and recruitment are performing as hoped. No interim primary endpoint analysis is planned. Full data analysis will commence once recruitment and data collection are complete, and the REDCap database is locked.

Safety reporting

Data on serious adverse events (SAEs: as described by good clinical practice guidelines) and adverse events (AEs) will be collected during the trial visits and continuously throughout the trial. All SAEs will be reported to the sponsor within 24 hours of notification and will be followed until resolution. SAEs in this study include participant hospitalisation for any treatment, including elective admissions, for any condition including pre-existing conditions. Anticipated AEs for this trial include participants requiring antibiotics or hospitalisation for a pulmonary exacerbation; adverse reactions to prescribed medications; natural fluctuations in patient symptoms and minor muscle aches consistent with completion of yoga.

Trial amendments

The study details reported here are described within the trial protocol version 1.4 (date: 27 February 2025). There has been one substantial protocol amendment which added questions about barriers to completion of yoga classes to the week 12 postyoga assessment questionnaire which was granted ethical approval by the South-Yorkshire and Humber REC on 3 April 2025. There have been 15 non-substantial protocol amendments, a summary of which is provided in the online supplemental material. Protocol amendments will be communicated to sites and other relevant parties through email.

Publication and dissemination

All participants will receive a lay summary of results on study completion and will be invited to attend a trial results and feedback webinar. Trial results will be presented at national and international conferences, and local scientific meetings of Imperial College, London and RBH. A report on results will be submitted to the trial funder (Vertex). Publication will be pursued in a relevant peer-reviewed scientific journal. Requests for data sharing of individual deidentified participant data (including data dictionary) and statistical code will be considered by the trial team.

Data availability statement

No data are available.