A CFit Study - Acute Exercise

NCT03237767 | Terminated DMC

• 1 other identifier: ZS003
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

A great medical success is the increase in the median survival age associated with cystic fibrosis (CF). However, this success has led to a new era of research aiming to maximise the quality of life (QoL) of the aging CF population. Over recent decades, exercise training has become an integral part of CF management by improving ones aerobic exercise function and QoL. However, the effects exercise training has upon other aspects of the disease, e.g. metabolic and vascular abnormalities, remains largely unknown. The increased survival age associated with CF means the non-pulmonary co-morbidities are becoming increasingly prevalent and clinically important. For example, CF-related diabetes (CFRD) is one of the most common non-pulmonary co-morbidities of CF, and is associated with patients having a poorer pulmonary function and nutritional state, which ultimately leads to a worsened prognosis. Despite the efficacy of exercise training to manage dysglycaemia in other populations (e.g. type 2 diabetes mellitus only a single study has investigated its efficacy in patients with CF, whereby authors reported various encouraging findings (e.g. an improved OGTT score and insulin sensitivity). The present study aims to build on previous trials by comparing the therapeutic effects of a single session of high-intensity interval exercise (HIIE) and moderate intensity exercise (MIE) upon the 24 hour, ambulatory glycaemic profile of patients with CF. Additionally, the present study will identify whether HIIE and/or MIE can mediate the consequences of transient hyperglycaemia when considering: biomarkers of inflammation, oxidative stress and nitric oxide (NO2) bioavailability, as well as functional measures of microvascular endothelial function. The present study supports the top 10 research priorities set by the CF Trust, by further investigating the potential for exercise training to prevent/manage multiple aspects of CF, including dysglycaemia.

Conditions

Cystic Fibrosis; Cystic Fibrosis-related Diabetes

Outcome Measures

Primary Outcomes (3)

• Glucose concentration before and after oral glucose tolerance test

  Glucose concentration before and after oral glucose tolerance test (which follows an exercise training session)

  Visit 1 (pre glucose ingestion after exercise completed and 30, 60, 90, 120 and 180 minutes following glucose ingestion), Visit 2 (pre glucose ingestion after exercise completed and 30, 60, 90, 120 and 180 minutes following glucose ingestion)

• Insulin concentration before and after oral glucose tolerance tolerance

  Insulin concentration before and after oral glucose tolerance test (which follows an exercise training session)

  Visit 1 (pre glucose ingestion after exercise completed and 30, 60, 90, 120 and 180 minutes following glucose ingestion), Visit 2 (pre glucose ingestion after exercise completed and 30, 60, 90, 120 and 180 minutes following glucose ingestion)

• Glycaemic control (measured using arm-mounted Freestyle Libre continuous glucose monitor)

  Glycaemic control fixed to the arm will measure glucose excursions continuously

  Continuous measurement through study completion (2 week period)

Secondary Outcomes (13)

• Nitrotyrosine (NT)

  Visit 1 and 2: pre-exercise (baseline) and 1 h following exercise 75 g glucose is ingested: NT measured immediately before glucose ingestion and 120 minutes after

• Total cysteine (tCys)

  Visit 1 and 2: pre-exercise (baseline) and 1 h following exercise 75 g glucose is ingested: tCys measured immediately before glucose ingestion and 120 minutes after

• Total glutathione (tGSH)

  Visit 1 and 2: pre-exercise (baseline) and 1 h following exercise 75 g glucose is ingested: tGSH measured immediately before glucose ingestion and 120 minutes after

• Tumor necrosis factor alpha (TNF-alpha)

  Visit 1 and 2: pre-exercise (baseline) and immediately post-exercise, additionally 1 h following exercise 75 g glucose is ingested: TNF-alpha measured immediately before glucose ingestion and 60, 120 and 180 minutes after)

• Soluble vascular cell adhesion molecule (sVCAM-1)

  Visit 1 and 2: pre-exercise (baseline) and immediately post-exercise, additionally 1 h following exercise 75 g glucose is ingested: sVCAM-1 measured immediately before glucose ingestion and 60, 120 and 180 minutes after)

Study Arms (2)

Moderate vs. High-intensity exercise (randomised)

EXPERIMENTAL

Compare the effects of a single session of moderate continuous exercise versus high-intensity interval exercise (MIE completed first)

Other: MIE; Other: HIIE

High-intensity vs. Moderate intensity exercise (randomised)

EXPERIMENTAL

Compare the effects of a single session of moderate continuous exercise versus high-intensity interval exercise (HIIE completed first)

Other: MIE; Other: HIIE

Interventions

MIE OTHER

The moderate intensity exercise (MIE) condition will begin and end with an appropriate warm-up (3 minutes at 20 W) and cool-down (2 minutes at 20 W), respectively. Throughout all exercising procedures, participants will maintain a pedal cadence of 60-80 rpm, with the average being noted and kept consistent between trials. Additionally, verbal encouragement will be given depending on the participant's preference, and kept consistent between visits. The MIE bout will be in coherence with the physical activity guidelines for people with CF (150 min/week of moderate to vigorous physical activity). For the MIE, participants will cycle for approximately 30 minutes at 90% of their gas exchange threshold.

High-intensity vs. Moderate intensity exercise (randomised); Moderate vs. High-intensity exercise (randomised)

HIIE OTHER

The high-intensity interval exercise (HIIE) condition will begin and end with an appropriate warm-up (3 minutes at 20 W) and cool-down (2 minutes at 20 W), respectively. Throughout all exercising procedures, participants will maintain a pedal cadence of 60-80 rpm, with the average being noted and kept consistent between trials. Additionally, verbal encouragement will be given depending on the participant's preference, and kept consistent between visits. The HIIE will be matched for the projected work done during the MIE. The HIIE protocol has been extrapolated from recent reports which have shown improvements in glycaemic control and vascular endothelial function. Specifically, participants will cycle at 90% of their peak power output for 60 seconds, followed by 60 seconds of active recovery.

High-intensity vs. Moderate intensity exercise (randomised); Moderate vs. High-intensity exercise (randomised)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 12 years of age
• CF diagnosis based on clinical features, supported by an abnormal sweat test (sweat chloride \> 60 mmol·L-1 \> 100 mg sweat) and, where possible, diagnostic genotyping
• No contraindications to performing exhaustive exercise
• Can understand and cooperate with the study protocol
• No increase in symptoms or weight loss in the preceding 2 weeks

You may not qualify if:

• 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
• Onset of acute infection
• Becomes and/or is tested to be pregnant following enrolment to the study
• Experiences significant hypoxaemia during visit 2 of the CFit\_BL protocol (IRAS ID: 225310) which requires supplemental O₂. Under these circumstances, participants will be invited to continue their participation under the CFit\_BL trial (IRAS ID: 225310)
• Unable to understand or cooperate with study protocol
• The individual does not wish to participate further

Sponsors & Collaborators

• University of Portsmouth: lead
• Queen Alexandra Hospital, Portsmouth: collaborator
• University Hospital Southampton NHS Foundation Trust: collaborator
• Loughborough University: collaborator

Study Sites (1)

Department of Sport and Exercise Science

Portsmouth, Hampshire, PO1 2ER, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The present study will be a pilot, counter-balanced, cross-over trial in individuals with CF.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer in Physical Activity, Exercise and Health

Model Details: The present study will be a pilot, counter-balanced, cross-over trial in individuals with CF.

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: August 3, 2017
• Study Start: May 1, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: April 28, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)