Effects of physical activity and exercise on glycaemic control in cystic fibrosis

Participants who meet the inclusion criteria will be invited to participate in a 10 day research study when they attend a routine Royal Prince Alfred Cystic Fibrosis(CF) clinic appointment. If they provide consent to participate in the study, they will be provided with a continuous flash glucose monitor (CGM, FreeStyle LibreTM 2 Abbott Diabetes Care) and an activity monitor (activPALTM, PAL Technologies) either at CF clinic or by mail. The FreeStyle LibreTM 2 is a standard device used for glucose monitoring in diabetes clinics worldwide . Instructions on how to use the CGM will be provided by the CF Clinic diabetes educator either in person or via telehealth at the start of the trial. The activPAL is a validated device used for activity monitoring, including analyses of physical activity and sedentary behaviour . Instructions on how to use the activPAL device will be provided by one of the Physiotherapists involved in the trial. The first day of CGM and activity monitoring will be Day 1 of the trial. Participants will be instructed to maintain their usual physical activity and exercise routines, as well as continue their usual diet and medication regimens for the study period. CF participants will be asked to complete four questionnaires at study entry: Clarkes hypoglycaemia awareness survey; participant hypoglycaemia questionnaire; Edinburgh hypoglycaemia symptom scale and the CFQ-R, a CF-specific health-related quality of life questionnaire . The questionnaires will be completed securely online via REDCap. Healthy control participants will be invited to complete the same questionnaires, except for the CFQ-R (for a total of three questionnaires). Participants will be provided with a one page activity, food and insulin diary to record sleeping and waking times, details of any exercise, timing and carbohydrate content of meals, and if prescribed, timing and dosage of insulin. Patients will be advised to use usual prandial insulin before exercise as per their usual routine. The participants will then be booked to have one 20-minute moderate intensity exercise session at the Queen Elizabeth II Pulmonary Rehabilitation, Royal Prince Alfred Hospital, Camperdown, NSW, between Day 4 and Day 8. The exercise will be performed on a stationary cycle (Ergoselect 5, ergoline GmbH, Germany) and participants will be monitored according to standard protocols for the Exercise Lab (ECG, oxygen saturation, blood pressure and metabolic measures). This session will be supervised and tailored for each patient by one of the physiotherapists involved in the study, who all have expertise in exercise testing and training. The workload on the cycle will be titrated to achieve 60-70% of estimated peak heart rate and a reported breathlessness score of moderate-somewhat severe, as per pulmonary rehabilitation guidelines. A physician will also be available to provide supervision if needed. Participants will be observed for one hour after completion of the exercise session and provided with a hypoglycaemia kit (fast and long acting carbohydrate) if they show any sign of hypoglycaemia. They are then able to return home and will be advised to perform their regular activity and exercise routines at any time convenient to them until trial completion at Day 10. After completion of the study (Day 11), the participants can discard the CGM in a biohazard sharps bin in their own home. This will be provided to them. Glucose monitoring results will be remotely downloaded using LibreviewTM as per current standard of care, a cloud platform allowing access to glucose data with established security protocols. This secure, protected cloud-based diabetes management system allows glucose readings to be uploaded from LibreLink systems and reviewed. For both patients and healthcare professionals to access LibreviewTM they must have an account which is password protected. Healthcare professionals must also be approved by admin of the ‘Practice’ so that they can access patient’s glucose readings. Post-TrikaftaTM study If Trikafta becomes available on the PBS between 2021 and 2023, participants who completed the pre-Trikafta component of the study will be invited to complete this study a second time, after 4 weeks post Trikafta initiation. Approximately 90 % of patients with CF will become eligible for this medication once on PBS and will become standard of care. This is an oral medication that is used twice a day at the dose of 100/50/75 mg. Monitoring of adherence will be usual clinically practice as well as usual monitoring with required pathology testing. This medication will be used ongoing unrelated to the study process. There will be no changes for the previously described protocol except that they will now be on a new medication. The data of the post Trikafta group will be compared to exercise only group as well as healthy volunteers. Healthy Control Participants Healthy control (HC) participants without CF will be recruited via advertisement placed in the clinic waiting room. Body Composition Substudy: Participants will also be invited to undergo a body composition scan at the RPAH Endocrine department prior to their exercise study at the QEII gym.