Clinical trial NCT05857709: Fitness, Body Composition, Physical Activity and Sleep Patterns in People With Cystic Fibrosis on Modulator Therapy.
Official title: An Observational Study to Understand the Fitness, Body Composition, Physical Activity and Sleep Patterns in People With Cystic Fibrosis on Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy Compared to Healthy Controls
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cystic Fibrosis
Keywords: Exercise
Modulator therapy
Peripheral muscle function
Vascular function
Body composition
Physical activity
Lead sponsor: University of Portsmouth
Sponsor class: OTHER
Collaborators: name: University Hospital Southampton NHS Foundation Trust
First posted: 2023-05-15
Enrollment: 100
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be recruited from adult and paediatric CF outpatient clinics within the Southampton CF network.

Brief summary: 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.

Detailed description: 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 criteria: 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

Primary outcomes:
measure: Maximal oxygen uptake
timeFrame: Day 1 - baseline
Secondary outcomes:
measure: Peak minute ventilation
timeFrame: Day 1 - baseline
measure: Oxygen uptake at the gas exchange threshold
timeFrame: Day 1 - baseline
measure: Peak power output
timeFrame: Day 1 - baseline
measure: Time to exhaustion
timeFrame: Day 1 - baseline
measure: Heart rate
timeFrame: Day 1 - baseline
measure: Near-infrared spectroscopy derived deoxygenated [haemoglobin + myoglobin]
timeFrame: Day 1 - baseline
measure: Cardiac output
timeFrame: Day 1 - baseline
measure: Stroke volume index
timeFrame: Day 1 - baseline
measure: Forced Expiratory Volume in the 1st second (% predicted)
timeFrame: Day 1 - baseline
measure: Forced Vital Capacity (%predicted)
timeFrame: Day 1 - baseline
measure: Total minutes of physical activity (light, moderate, moderate to vigorous physical activity)
timeFrame: Physical activity will be measured continuously for 7 days
measure: Sleep efficiency (time in bed + time asleep)
timeFrame: Sleep efficiency will be measured continuously for 7 days
measure: Acetylcholine iontophoresis
timeFrame: Day 1 - baseline
measure: Insulin iontophoresis
timeFrame: Day 1 - baseline
measure: Percentage change in brachial artery diameter taken from the Flow Mediated Dilation assessment
timeFrame: Day 1 - baseline
measure: Maximum quadricep strength
timeFrame: Day 2 - baseline
measure: Quadricep fatigability index
timeFrame: Day 2 - baseline
measure: Handgrip strength
timeFrame: Day 2 - baseline
measure: Sit to stand repetitions per minute
timeFrame: Day 2 - baseline
measure: Body composition (total fat-free mass and total fat mass)
timeFrame: Day 2 - baseline
measure: Habitual activity estimation scale
timeFrame: Day 2 - baseline
measure: Cystic fibrosis questionnaire revised
timeFrame: Day 2 - baseline
measure: The Pittsburgh Sleep Quality Index
timeFrame: Day 2 - baseline
measure: Perceived exertion (breathing effort, chest tightness, throat narrowing, perceived exertion)
timeFrame: Day 1 - baseline
Other outcomes:
Locations:
city: Portsmouth
country: United Kingdom
facility: University of Portsmouth
Study officials:
References: