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

Recruiting
Conditions
Cystic Fibrosis
Registration Number
NCT05896488
Lead Sponsor
University of Portsmouth
Brief Summary

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®.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
18
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Sweat sodium concentration (mmol∙L-1)Day 2 - baseline

Between group differences in sweat sodium concentration

Secondary Outcome Measures
NameTimeMethod
Cutaneous blood fluxDay 2 - baseline

Between group differences in cutaneous blood flux

Heat sensitivityDay 2 - baseline

Between group differences in heat sensitivity derived from sweat rate / change in thermal comfort

Whole-body sweat rate (mL)Day 2 - baseline

Between group differences in whole-body sweat rate derived from pre - post nude body mass

Forearm sweat rate (mg∙min-1∙cm2)Day 2 - baseline

Between group differences in forearm sweat rate

Mid-back sweat rate (mg∙min-1∙cm2)Day 2 - baseline

Between group differences in mid-back sweat rate

Sweat gland activity (gland∙cm2)Day 2 - baseline

Between group differences in sweat-gland activation derived from the modified-iodine patch technique

Core temperature (°C)Day 2 - baseline

Between group differences in core temperature derived from rectal temperature

Mean skin temperature (°C)Day 2 - baseline

Between group differences in skin temperature

Change in thermal comfortDay 2 - baseline

Between group differences in change in thermal comfort

Maximal oxygen uptake (VO2 max)Day 1 - baseline

Between group differences in oxygen uptake derived from a maximal cardiopulmonary exercise test

Heart rate (b∙min-1)Day 2 - baseline

Between group differences in heart rate

Urine osmolality (mOsmol/kg)Day 2 - baseline

Between group differences in urine osmolality

Perception of thermal comfortDay 2 - baseline

Between group differences in perception of thermal comfort

Perception of temperature sensationDay 2 - baseline

Between group differences in perception of temperature sensation

Rate of change in thermal comfortDay 2 - baseline

Between group differences in rate of change in thermal comfort

Heat illness symptom indexDay 2 - baseline

Between group differences in heat-related illness symptoms

Trial Locations

Locations (1)

University of Portsmouth

🇬🇧

Portsmouth, United Kingdom

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