Fitness, Body Composition, Physical Activity and Sleep Patterns in People With Cystic Fibrosis on Modulator Therapy.

University of Portsmouth100 enrolled

Overview

Cystic fibrosis (CF) is the most common inherited condition in the United Kingdom, affecting approximately 10,837 people. It is well recognised that regular exercise is clinically important for people with CF. Exercise function measured by the maximal oxygen consumption during a cardiopulmonary exercise test is often reduced in people with CF and this has been attributed to multiple factors including, altered heart and blood vessel function, muscle function, reduced physical activity levels and poorer sleep quality. New medicine (modulators) have become available for many people with CF. Modulators appear able to reduce sweat chloride concentrations, improve lung function and reduce the frequency of pulmonary exacerbations in people with CF. Little evidence exists to show how they may have changed the fitness and underlying mechanisms responsible for this in people with CF. This study aims to: 1. determine the exercise function 2. determine the blood vessel function 3. determine body composition 4. determine physical activity and sleep levels in people with CF on modulator therapy compared to a healthy controls group.

CF is the most common inherited condition in the United Kingdom, affecting approximately 10,837 people. CF affects the movement of salt and water across the body which leads to a thick sticky build up of mucus causing problems in the lungs and digestive system. CF also causes problems in other parts of the body for example, the heart, the blood vessels and muscles. This can impact a person with CFs' ability to exercise which can have impact prognosis, quality of life and increase the amount of times someone with CF is admitted to hospital due to a chest infection. For many people with CF, new medicine (modulators) have lately become accessible bringing big changes to their health. Elexacaftor-tezacaftor-ivacaftor (ETI) is the most recently approved modulator for use in people with specific CF transmembrane conductance regulator gene mutations and is now the most widely used modulator therapy. So far clinical trials have largely looked at lung function, sweat chloride levels and body mass index. The wider reaching effects of modulator therapy on exercise function has not been studied. This study will see if people with CF have blood vessel and exercise dysfunction, abnormal body composition and reduced physical activity and sleep quality when they are taking modulator therapy compared to a healthy group. The aims of this study are: 1. Determine the aerobic exercise function and mechanisms underlying this in people with CF stable on ETI and whether this is different to healthy age- and sex-matched controls; 2. Determine the peripheral muscle function in people with CF stable on ETI and whether this is different to healthy age- and sex-matched controls; 3. Determine the functional exercise capacity in people with CF stable on ETI and whether this is different to healthy age- and sex-matched controls; 4. Determine the micro- and macrovascular endothelial function in people with CF stable on ETI and whether this is different to healthy age- and sex-matched controls; 5. Determine body composition in people with CF stable on ETI and whether this is different to healthy age- and sex-matched controls; 6. Determine the physical activity levels and sleep duration and quality in people with CF stable on ETI and whether this is different to healthy age- and sex-matched controls This study will recruit 50 people with CF and 50 healthy age- and sex-matched control participants who are older than 10 years of age. It will ask them to attend the University of Portsmouth for 2 visits. The first visit will last \~3 hours. During this time they will undergo measures on blood vessel function and aerobic exercise function. The second visit will last \~2 hours. During this time they will undergo a body composition scan and a series of muscle function test. At home, participants will wear an accelerometer for 7 days and complete a series of questionnaires.

Eligibility

Sex: ALLMin age: 10 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria for participants with cystic fibrosis: * Stable on the modulator therapy, Kaftrio® * Males and females ≥ 10 years of age * CF diagnosis based on clinical features, supported by a history of an abnormal sweat test (sweat chloride \> 60 mmol·L-1 \> 100 mg sweat), where possible, diagnostic genotyping would also be desired * Can clearly state that they are not pregnant * No contraindications to performing exercise * Can understand and cooperate with the study protocol * No increase in symptoms or weight loss in the preceding 2 weeks Inclusion criteria for healthy control participants: * Healthy males and females who are age- and sex-matched to the enrolled individuals with CF * Can clearly state that they are not pregnant * No clinical diagnosis of a chronic disease * Can understand and cooperate with the study protocol * No contraindications to performing exhaustive exercise Exclusion criteria for participants with cystic fibrosis: * Any non-pulmonary conditions that may impair exercise ability, such as musculoskeletal disorders and cardiovascular disease. * Unstable co-morbid asthma (daily pulmonary function variability of \>20%) * Is pregnant during the initial screening process * Unable to understand or cooperate with the study protocol due to learning difficulties or otherwise * Not of a suitable age for testing * Is a smoker or inhales any other substances * Are taking vasoactive medications Exclusion criteria for healthy control participants: * Any pulmonary, metabolic or cardiovascular conditions * Any other diagnosed disease * Any non-pulmonary conditions that may impair exercise ability, such as musculoskeletal disorders and cardiovascular disease * Is pregnant during the initial screening procedure * Presents with co-morbidities to performing exhaustive exercise * Is a smoker or inhales any other substance * Unable to understand or cooperate with the study protocol due to learning difficulties or otherwise * Not an age- or sex-match for the CF group * Are taking vasoactive medications

Outcomes

Primary Outcomes

Maximal oxygen uptake

Between group differences in maximal oxygen uptake derived from a maximal cardiopulmonary exercise testing on a cycle ergometer

Time frame: Day 1 - baseline

Secondary Outcomes

Peak minute ventilation

Between group differences in peak minute ventilation derived from a maximal cardiopulmonary exercise test on a cycle ergometer

Time frame: Day 1 - baseline

Oxygen uptake at the gas exchange threshold

Between group differences in oxygen uptake at the gas exchange threshold derived from a maximal cardiopulmonary exercise test on a cycle ergometer

Time frame: Day 1 - baseline

Peak power output

Between group differences in peak power output derived from a maximal cardiopulmonary exercise test on a cycle ergometer

Time frame: Day 1 - baseline

Time to exhaustion

Between group differences in time to exhaustion derived from a maximal cardiopulmonary exercise test on a cycle ergometer

Time frame: Day 1 - baseline

Heart rate

Between group differences in heart rate derived from a maximal cardiopulmonary exercise test on a cycle ergometer

Time frame: Day 1 - baseline

Near-infrared spectroscopy derived deoxygenated [haemoglobin + myoglobin]

Between group differences in dynamics of near-infrared spectroscopy derived deoxygenated \[haemoglobin + myoglobin\]

Time frame: Day 1 - baseline

Cardiac output

Between group differences in dynamics of non-invasive thoracic impedance cardiography

Time frame: Day 1 - baseline

Stroke volume index

Between group differences in dynamics of non-invasive thoracic impedance cardiography

Time frame: Day 1 - baseline

Forced Expiratory Volume in the 1st second (% predicted)

Between group differences in Forced Expiratory Volume in the 1st second measured using flow-volume loop spirometry

Time frame: Day 1 - baseline

Forced Vital Capacity (%predicted)

Between group differences in Forced Vital Capacity measured using flow-volume loop spirometry

Time frame: Day 1 - baseline

Total minutes of physical activity (light, moderate, moderate to vigorous physical activity)

Between group differences in physical activity assessed via wrist-worn accelerometery

Time frame: Physical activity will be measured continuously for 7 days

Sleep efficiency (time in bed + time asleep)

Between group differences in sleep efficiency assessed via wrist-worn accelerometery

Time frame: Sleep efficiency will be measured continuously for 7 days

Acetylcholine iontophoresis

Between group differences in acetylcholine iontophoresis measure of microvascular function

Time frame: Day 1 - baseline

Insulin iontophoresis

Between group differences in insulin iontophoresis measure of microvascular function

Time frame: Day 1 - baseline

Percentage change in brachial artery diameter taken from the Flow Mediated Dilation assessment

Between group differences in Flow Mediated Dilation assessment derived from baseline brachial artery diameter and peak brachial artery diameter from flow mediated dilation measure of macrovascular function

Time frame: Day 1 - baseline

Maximum quadricep strength

Derived from a maximal voluntary contraction

Time frame: Day 2 - baseline

Quadricep fatigability index

Derived from change in maximal voluntary contraction

Time frame: Day 2 - baseline

Handgrip strength

Between group difference in handgrip strength

Time frame: Day 2 - baseline

Sit to stand repetitions per minute

Between group difference in sit to stand repetitions per minute

Time frame: Day 2 - baseline

Body composition (total fat-free mass and total fat mass)

Derived from dual-energy X-ray absorptiometry

Time frame: Day 2 - baseline

Habitual activity estimation scale

Between group difference in habitual activity estimation scale - answers are varied and require numerical values, percentages and/or multiple choice questions

Time frame: Day 2 - baseline

Cystic fibrosis questionnaire revised

Between group difference in health related quality of life on a 0 - 100 scale with higher scores indicating better health related quality of life

Time frame: Day 2 - baseline

The Pittsburgh Sleep Quality Index

Between group differences in the Pittsburgh Sleep Quality Index on a 0 - 21 scale with higher scores indicating worse sleep quality

Time frame: Day 2 - baseline

Perceived exertion (breathing effort, chest tightness, throat narrowing, perceived exertion)

Between group differences in perceived exertion using the Dalhousie Dyspnoea and Perceived Exertion Scales during a maximal cardiopulmonary exercise testing on a cycle ergometer on a 1 - 7 scale with a higher value indicating a worse perceived exertion

Time frame: Day 1 - baseline

Fitness, Body Composition, Physical Activity and Sleep Patterns in People With Cystic Fibrosis on Modulator Therapy.

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts