Fitness, Body Composition, Physical Activity and Sleep Patterns in People With Cystic Fibrosis on Modulator Therapy. (Understand-CF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis

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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Zoe Saynor; Phone Number: 02392843080; Email: zoe.saynor@port.ac.uk
• Study Contact Backup: Name: Lauren Clayton; Phone Number: 02392843085; Email: lauren.clayton@port.ac.uk

Study Locations

• United Kingdom
  • Portsmouth, United Kingdom, PO1 2EF
    • Recruiting
    • University of Portsmouth
    • Contact: Zoe Saynor; Phone Number: 3080 023 9284 3080; Email: zoe.saynor@port.ac.uk
    • Contact: Lauren Clayton; Phone Number: 3085 023 9284 3085; Email: lauren.clayton@port.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from adult and paediatric CF outpatient clinics within the Southampton CF network.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cystic fibrosis; No intervention - only assessments.
Healthy Control; No intervention - only assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal oxygen uptake	Between group differences in maximal oxygen uptake derived from a maximal cardiopulmonary exercise testing on a cycle ergometer	Day 1 - baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 1 - baseline
Peak power output	Between group differences in peak power output derived from a maximal cardiopulmonary exercise test on a cycle ergometer	Day 1 - baseline
Time to exhaustion	Between group differences in time to exhaustion derived from a maximal cardiopulmonary exercise test on a cycle ergometer	Day 1 - baseline
Heart rate	Between group differences in heart rate derived from a maximal cardiopulmonary exercise test on a cycle ergometer	Day 1 - baseline
Near-infrared spectroscopy derived deoxygenated [haemoglobin + myoglobin]	Between group differences in dynamics of near-infrared spectroscopy derived deoxygenated [haemoglobin + myoglobin]	Day 1 - baseline
Cardiac output	Between group differences in dynamics of non-invasive thoracic impedance cardiography	Day 1 - baseline
Stroke volume index	Between group differences in dynamics of non-invasive thoracic impedance cardiography	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	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	Sleep efficiency will be measured continuously for 7 days
Insulin iontophoresis	Between group differences in insulin iontophoresis measure of microvascular function	Day 1 - baseline
Maximum quadricep strength	Derived from a maximal voluntary contraction	Day 2 - baseline
Quadricep fatigability index	Derived from change in maximal voluntary contraction	Day 2 - baseline
Handgrip strength	Between group difference in handgrip strength	Day 2 - baseline
Sit to stand repetitions per minute	Between group difference in sit to stand repetitions per minute	Day 2 - baseline
Body composition (total fat-free mass and total fat mass)	Derived from dual-energy X-ray absorptiometry	Day 2 - baseline
Peak minute ventilation	Between group differences in peak minute ventilation derived from a maximal cardiopulmonary exercise test on a cycle ergometer	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	Day 1 - baseline
Forced Vital Capacity (%predicted)	Between group differences in Forced Vital Capacity measured using flow-volume loop spirometry	Day 1 - baseline
Acetylcholine iontophoresis	Between group differences in acetylcholine iontophoresis measure of microvascular function	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	Day 1 - 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	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	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	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	Day 1 - baseline

Collaborators and Investigators

• Sponsor: University of Portsmouth
• Collaborators: University Hospital Southampton NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2023
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: May 9, 2023
• First Posted (Actual): May 15, 2023

Study Record Updates

• Last Update Posted (Actual): May 18, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Exercise; Physical activity; Body composition; Vascular function; Modulator therapy; Peripheral muscle function
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 313567

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No