A CFit Study - Baseline

NCT03234387 | Terminated DMC

• 1 other identifier: ZS002
• Study Type: observational
• Target: 10
• 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 with the aim to maximise the quality of life (QoL) of the aging CF population. Recent research has demonstrated that the traditional method of determining disease progression, i.e. pulmonary function, no longer adequately predict survival rates. Therefore, various bodies have promoted cardiopulmonary exercise testing (CPET), as outcomes from this test (e.g. one's maximal O2 uptake \[VO₂max\]) are known predictors of the QoL, risk of hospitalisation and prognosis of individuals with CF. One of the most common non-pulmonary co-morbidities of CF is CF-related diabetes (CFRD). Importantly, CFRD is associated with a poorer pulmonary function compared to CF patients without CFRD, and ultimately a worsened prognosis. Despite this, the influence an impaired glycaemic control has upon the VO₂max derived from a CPET is unknown in CF. Therefore, the present study aims to assess whether VO₂max, an established determinant of QoL, differs between patients with CF with and without established CFRD as well as a group of age- and gender-matched healthy control subjects. The additional measures within the present study, such as: biomarkers of inflammation, redox balance and nitric oxide (NO2) bioavailability, as well as functional measures of microvascular endothelial function will aid our knowledge of the physiological abnormalities which are a cause or consequence of CFRD. Importantly, by identifying the factors which may contribute to CFRD progression and those that are viable for early intervention, mean the aims and objectives of this study are compatible with the top 10 research objectives set by the CF Trust.

Conditions

Cystic Fibrosis (CF); Cystic Fibrosis-related Diabetes

Outcome Measures

Primary Outcomes (1)

• Maximal oxygen uptake (aerobic fitness)

  Maximal oxygen uptake (aerobic fitness) from a maximal cardiopulmonary exercise testing on a cycle ergometer

  Visit 1 - Baseline

Secondary Outcomes (20)

• VO2 gain

  Visit 1 - Baseline

• VO2 mean response time

  Visit 1 - Baseline

• Gas exchange threshold

  Visit 1 - Baseline

• Near-infrared spectroscopy derived deoxygenated [haemoglobin + myoglobin]

  Visit 1 - Baseline

• Pulmonary function

  Visit 1 (baseline), Visit 2 (baseline)

Study Arms (3)

Cystic fibrosis (CF) with established CF-related diabetes

Cystic fibrosis (CF) with established CF-related diabetes Inclusion criteria: * 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 * Established CFRD in accordance with the most recent American Diabetes Association positional statement\]. This statement recommends CFRD is diagnosed using a 2 hour OGTT. However, the present study will also include those based on fasting plasma glucose and glycated hemoglobin levels, when symptoms of diabetes are also present: * 2 hour OGTT plasma glucose ≥ 200 mg.dL-1 (11.1 mmol.L-1) * Fasting plasma glucose ≥ 126 mg.dL-1 (7.0 mmol.L-1) * Glycated hemoglobin ≥ 48 mmol/mol * 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

Other: No intervention - only assessments.

Cystic fibrosis (CF) without established CF-related diabetes

Cystic fibrosis (CF) without established CF-related diabetes Inclusion criteria: * 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), where possible, diagnostic genotyping would also be desired * No evidence of established, gestational or exacerbation induced CFRD in accordance with the American Diabetes Association criteria (stated above; \[110\]). * 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

Other: No intervention - only assessments.

Healthy controls

Age- and gender-matched healthy control participants.

Other: No intervention - only assessments.

Interventions

No intervention - only assessments. OTHER

No intervention only a number of assessments. Participants will be assessed during a maximal cardiopulmonary exercise testing on an exercise bike during 1 visit, and before and after an oral glucose tolerance test on a following visit.

Also known as: Exercise testing, Insulin and acetylcholine iontophoresis measures of microvascular function, Oral glucose tolerance test (75 g glucose)

Cystic fibrosis (CF) with established CF-related diabetes; Cystic fibrosis (CF) without established CF-related diabetes; Healthy controls

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Individuals with cystic fibrosis (CF) and established CF-related diabetes (CFRD) * Individuals with CF and no established CFRD (age- and gender-matched to CFRD group) * Healthy age- and gender-matched control participants (matched to CFRD group)

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
• Established CFRD in accordance with the most recent American Diabetes Association positional statement. This statement recommends CFRD is diagnosed using a 2 hour OGTT. However, the present study will also include those based on fasting plasma glucose and glycated hemoglobin levels, when symptoms of diabetes are also present:
• hour OGTT plasma glucose ≥ 200 mg.dL-1 (11.1 mmol.L-1)
• Fasting plasma glucose ≥ 126 mg.dL-1 (7.0 mmol.L-1)
• Glycated hemoglobin ≥ 48 mmol/mol
• 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
• GROUP 2:
• Cystic fibrosis (CF) without established CF-related diabetes:
• 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), where possible, diagnostic genotyping would also be desired
• No evidence of established, gestational or exacerbation induced CFRD in accordance with the American Diabetes Association criteria (stated above).
• 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
• 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%)

Sponsors & Collaborators

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

Study Sites (1)

Department of Sport and Exercise Science

Portsmouth, Hampshire, PO1 2ER, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Acellular plasma will be stored at - 80 degrees

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Exercise Test; Insulin; Glucose Tolerance Test; Glucose

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

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques, Endocrine; Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer in Physical Activity, Exercise and Health

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: July 31, 2017
• Study Start: November 17, 2017
• 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)