EASE-CF: Evaluating and addressing excess weight in adults with cystic fibrosis: a registry analysis and a feasibility randomised controlled trial with an embedded qualitative study.

In 2020, 90% of adults with cystic fibrosis (CF) in UK started CF transmembrane conductance regulator modulator treatments.

With these treatments, people have more stable disease and are likely to live longer, but the proportion of people living with overweight, and obesity has risen from 15% to 40%.

Helping people with CF to lose weight is challenging due to cognitive dissonance from historical advice to eat a high-energy diet, complex treatment plans, and concerns about reduction in lung function and fat-free mass.

There are no UK observational data detailing the clinical characteristics of this group and no trials of weight loss interventions to inform guidelines.

Research questions What are the clinical characteristics of adults with CF who have a BMI in the underweight, healthy weight, overweight and obesity categories? What are the associations between BMI and pre-specified CF related clinical characteristics? What is the acceptability and safety profile of the intervention?

Is it feasible to run a trial to test the intervention?

What are the barriers and facilitators to participation in a weight loss trial for people with CF and what is their experience of following a weight loss intervention? What is the experience of CF dietitians delivering this intervention?

Methods WP1: A cross-sectional analysis of UK CF registry data from ~6,000 adults to review the clinical characteristics of adults with CF by BMI category using descriptive and regression analysis. WP2: Multi-centre feasibility parallel randomised controlled trial. I will recruit 30 adults with CF and a BMI ≥27kg/m2 from 4 NHS CF centres.

Participants will be randomly allocated 2:1 to intervention to increase recruitment (12-week individualised meal plan programme with weekly dietetic support followed by 12 weeks of weight maintenance with fortnightly support) or to usual care (quarterly dietetic review). The CF-tailored intervention is being developed during my NIHR Predoctoral Clinical Academic Fellowship.

Remote visits will be at 4, 12, and 24 weeks.

Feasibility objectives ● Recruitment: reaching expected sample size in defined recruitment time period, ● Willingness to be randomised: proportion of eligible patients randomised. ● Intervention adherence: Median weight loss of at least 5% at 12 weeks. ● Retention: proportion of participants who attend final follow-up. ● Programme engagement: proportion of participants who attend more than 60% of intervention sessions.

WP3 An embedded qualitative study.

I will conduct framework analysis using semi-structured audio-recorded interviews with (a) all participants to explore the acceptability of the intervention and trial procedures and (b) 8 CF clinicians to explore the feasibility of delivery within routine care.

Impact The registry analysis will provide the first contemporary information on clinical characteristics of patients at each BMI category which will help to target the weight loss intervention. If the results indicate that a full trial is feasible, I will apply for funding for a definitive trial. Dissemination I will publish the protocol prospectively and the results in open-access, peer-reviewed journals.

I will present findings at CF conferences and share lay summaries with study participants and through the CF Trust.