Sweat Response, Sweat Composition and Thermoregulatory Response to Exercise in Heat in Adults With Cystic Fibrosis on Modulator Therapy. (Sweat-CF)

A Study to Assess the Sweat Response, Sweat Composition and Thermoregulatory Response to Exercise in Heat in Adults With Cystic Fibrosis on Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy Compared Healthy Controls.

Cystic fibrosis (CF) is a common inherited condition in the Caucasian population resulting in poor function and/or production of the CF transmembrane conductance regulator (CFTR) protein. The CFTR protein plays a crucial role in the secretion and re-absorption of sodium chloride within the sweat gland. The sweat gland has played a key role in diagnosing and understanding CF with sweat chloride elevation being a key criterion to diagnosing CF. People with CF are thought to be at risk of exertional heat illness during exposure to hot environments or during prolonged periods of exercise and are currently encouraged to take salt supplements during periods of excessive sweating.

Kaftrio®, a newly approved pharmacological therapy has shown a rapid and sustained reduction in sweat chloride levels on initiation of this treatment. This study will aim to play a crucial part in understanding the sweat response, sweat composition and the thermoregulatory response to exercise in the heat in people with CF on Kaftrio®.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis

Detailed Description

Cystic fibrosis (CF) is a common inherited condition in the Caucasian population, affecting approximately 52, 246 people in Europe. Mutations in the CF transmembrane conductance regulator (CFTR) gene results in poor function or production of the CFTR protein which functions as an anion channel to transport ions across the cell membrane.

The sweat gland has played a substantial part in diagnosing and understanding CF with sweat chloride elevation being a key criterion to diagnosing CF. Traditionally, abnormal function of the CFTR protein in the sweat gland results in failure to reabsorb sodium chloride leading to excessive salt loss. People with CF are thought to be at risk of exertional heat illness during exposure to hot environments or during prolonged periods of exercise and are currently encouraged to take salt supplements during periods of excessive sweating.

Over the last decade pharmacological therapies (CFTR modulator therapies (CFTRm)) which target the underlying cellular defect characterising CFTR in people with CF have been developed. Kaftrio® is now the most widely used modulator therapy. Studies have shown a rapid and sustained reduction in sweat chloride levels on initiation of these highly effective CFTRm. The need for salt supplementation may be influenced when taking CFTRm. Therefore, there is a need to further understand the sweat response relative to the needs in people with CF.

This study will recruit 9 people with CF who currently taking Kaftrio® and 9 healthy age-, sex- and weight-matched controls who are ≥ 18 years old. We will ask all participants to attend the laboratories for 2 visits. Visit 1 is designed to calculate metabolic heat production during different cycling intensities in order to set the workload for visit 2 relative to their metabolic heat production. Visit 2 is designed to collect sweat and thermoregulatory indices during 1 hour of cycling in the heat.

This study will compare the sweating and thermoregulatory response to exercising in the heat in a group of people with CF who are stable on Kaftrio® compared to a healthy matched control group.

The aims of this study are to:

1. Determine the sweat sodium concentration in adults with CF on Kaftrio® from exercise at a fixed-rate of metabolic heat production under heat stress conditions and whether this is different to healthy age- weight- and sex- matched controls;
2. Determine the local and whole-body sweat rate in adults with CF on Kaftrio® during exercise under heat stress conditions and whether this is different to healthy age- weight- and sex- matched controls;
3. Determine how adults with CF on Kaftrio® respond in terms of skin blood flow during exercise under heat stress conditions and whether this is different to healthy age- weight- and sex- matched controls;
4. Determine thermal strain from skin and core body temperature in adults with CF on Kaftrio® during exercise under heat stress conditions and whether this is different to healthy age- weight- and sex- matched controls.

• Study Type: Observational
• Enrollment (Estimated): 18

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: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from adult CF outpatient clinics within the CF network. If a potential participant outside of the CF network wishes to participant they will be screened by the CF consultants within the CF network.

Description

Inclusion Criteria for participants with CF:

• Is taking CFTRm
• Males and females ≥ 18 years of age
• CF diagnosis based on clinical features, supported by a history of an abnormal sweat test (sweat [Cl-] > 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 exhaustive exercise
• Can understand and cooperate with the study protocol
• No exacerbation (increase in cough, sputum or breathlessness, or change in the colour of sputum) within the preceding 2 weeks
• No weight loss in the preceding 2 weeks

Inclusion Criteria for healthy control participants:

• Healthy males and females who are age- weight- 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 CF:

• Any non-pulmonary conditions that may impair exercise ability, such as musculoskeletal disorders (arthritis, joint or muscle disease) and cardiovascular disease (congenital heart disease or cardiomyopathy).
• 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

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 (active arthritis, joint or muscle disease) and cardiovascular disease (congenital heart disease or cardiomyopathy)
• Is pregnant during the initial screening process
• Presents with co-morbidities to performing exhaustive exercise
• Is a smoker or inhales any other substances
• Unable to understand or cooperate with the study protocol due to learning difficulties or otherwise
• Not an age- weight- or sex-match for the CF group

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
Sweat sodium concentration (mmol∙L-1)	Between group differences in sweat sodium concentration	Day 2 - baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole-body sweat rate (mL)	Between group differences in whole-body sweat rate derived from pre - post nude body mass	Day 2 - baseline
Forearm sweat rate (mg∙min-1∙cm2)	Between group differences in forearm sweat rate	Day 2 - baseline
Mid-back sweat rate (mg∙min-1∙cm2)	Between group differences in mid-back sweat rate	Day 2 - baseline
Sweat gland activity (gland∙cm2)	Between group differences in sweat-gland activation derived from the modified-iodine patch technique	Day 2 - baseline
Core temperature (°C)	Between group differences in core temperature derived from rectal temperature	Day 2 - baseline
Mean skin temperature (°C)	Between group differences in skin temperature	Day 2 - baseline
Heart rate (b∙min-1)	Between group differences in heart rate	Day 2 - baseline
Cutaneous blood flux	Between group differences in cutaneous blood flux	Day 2 - baseline
Urine osmolality (mOsmol/kg)	Between group differences in urine osmolality	Day 2 - baseline
Perception of temperature sensation	Between group differences in perception of temperature sensation	Day 2 - baseline
Perception of thermal comfort	Between group differences in perception of thermal comfort	Day 2 - baseline
Change in thermal comfort	Between group differences in change in thermal comfort	Day 2 - baseline
Rate of change in thermal comfort	Between group differences in rate of change in thermal comfort	Day 2 - baseline
Heat sensitivity	Between group differences in heat sensitivity derived from sweat rate / change in thermal comfort	Day 2 - baseline
Heat illness symptom index	Between group differences in heat-related illness symptoms	Day 2 - baseline
Maximal oxygen uptake (VO2 max)	Between group differences in oxygen uptake derived from a maximal cardiopulmonary exercise test	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): March 18, 2023
• Primary Completion (Estimated): March 18, 2024
• Study Completion (Estimated): March 18, 2024

Study Registration Dates

• First Submitted: May 31, 2023
• First Submitted That Met QC Criteria: May 31, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Exercise, CFTR modulator therapy, thermoregulation, heat-related illness, sweat sodium
• 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: 315193

Drug and device information, study documents

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