Cystic Fibrosis-related Diabetes Clinical Trial
Official title:
A CFit Study: To What Extent Does Inflammation, Oxidative Stress, Nitric Oxide Bioavailability and Microvascular Endothelial Dysfunction Influence the Aerobic Exercise Function of Individuals With Cystic Fibrosis, With and Without Established Diabetes?
NCT number | NCT03234387 |
Other study ID # | ZS002 |
Secondary ID | |
Status | Terminated |
Phase | |
First received | |
Last updated | |
Start date | November 17, 2017 |
Est. completion date | December 1, 2020 |
Verified date | April 2021 |
Source | University of Portsmouth |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
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.
Status | Terminated |
Enrollment | 10 |
Est. completion date | December 1, 2020 |
Est. primary completion date | December 1, 2020 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 12 Years and older |
Eligibility | GROUP 1: 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 Exclusion Criteria: - 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: 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). - 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 Exclusion Criteria: - 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 - Not a suitable age- and gender-match for those with CFRD Exclusion during testing: - Onset of acute infection - Becomes and/or is tested to be pregnant following enrolment to the study - Unable to understand or cooperate with study protocol - The individual does not wish to participate further GROUP 3: Healthy age- and gender-matched control participants: Inclusion Criteria: - Age- and gender Exclusion Criteria: - Any non-pulmonary conditions that may impair exercise ability, such as musculoskeletal disorders (arthritis, joint or muscle disease), respiratory and cardiovascular disease (congenital heart disease or cardiomyopathy). - Is pregnant during the initial screening process - Unable to understand or cooperate with the study protocol due to learning difficulties or otherwise - Not a suitable age- and gender-match for those with CFRD Exclusion during testing: - Onset of acute illness or injury - Becomes and/or is tested to be pregnant following enrolment to the study - Unable to understand or cooperate with study protocol - The individual does not wish to participate further |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Department of Sport and Exercise Science | Portsmouth | Hampshire |
Lead Sponsor | Collaborator |
---|---|
University of Portsmouth | Loughborough University, Queen Alexandra Hospital, University Hospital Southampton NHS Foundation Trust |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximal oxygen uptake (aerobic fitness) | Maximal oxygen uptake (aerobic fitness) from a maximal cardiopulmonary exercise testing on a cycle ergometer | Visit 1 - Baseline | |
Secondary | VO2 gain | Oxygen cost of exercise (efficiency) - derived from maximal cardiopulmonary exercise test on a cycle ergometer | Visit 1 - Baseline | |
Secondary | VO2 mean response time | VO2 mean response time - derived from maximal cardiopulmonary exercise test | Visit 1 - Baseline | |
Secondary | Gas exchange threshold | Gas exchange threshold - derived from maximal cardiopulmonary exercise test | Visit 1 - Baseline | |
Secondary | Near-infrared spectroscopy derived deoxygenated [haemoglobin + myoglobin] | Dynamics of near-infrared spectroscopy derived deoxygenated [haemoglobin + myoglobin] | Visit 1 - Baseline | |
Secondary | Pulmonary function | Pulmonary function measured using flow-volume loop spirometry | Visit 1 (baseline), Visit 2 (baseline) | |
Secondary | Glycaemic control | Glycaemic control measured using an arm-mounted continuous glucose monitor | Glycaemic control will be measured continuously for 14 days following visit 1. | |
Secondary | Physical activity | Physical activity measured using a wrist-mounted physical activity monitor | Physical activity will be measured continuously for 14 days following visit 1. | |
Secondary | Dietary intake | Dietary intake measured using MyFitness Pal application and food diaries | Food diaries will be completed for 14 days following visit 1. | |
Secondary | Tumour necrosis factor alpha (TNF-alpha) | Tumour necrosis factor alpha (TNF-alpha) measured from plasma | Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test | |
Secondary | Soluble vascular cell adhesion molecule-1 (sVCAM) | Soluble vascular cell adhesion molecule-1 (sVCAM) measured from plasma | Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test | |
Secondary | Endothelin-1 (ET-1) | Endothelin-1 (ET-1) measured from plasma | Visit 1 (baseline and following maximal cardiopulmonary exercise test on cycle ergometer), Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test | |
Secondary | Interleukin-6 (IL-6) | Interleukin-6 (IL-6) measured from plasma | Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test | |
Secondary | [Nitrite] (NO2) | Nitrite concentration measured from plasma | Visit 1 (baseline ), Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test | |
Secondary | Nitrotyrosine (NT) | Nitrotyrosine (NT) measured from plasma | Visit 2: (baseline) and 120 minutes following ingestion of 75 g glucose for an oral glucose tolerance test | |
Secondary | Total glutathione (tGSH) | Total glutathione (tGSH) measured from plasma | Visit 2: (baseline) and 120 minutes following ingestion of 75 g glucose for an oral glucose tolerance test | |
Secondary | Total cysteine (tCys) | Total cysteine (tCys) measured from plasma | Visit 2: (baseline) and 120 minutes following ingestion of 75 g glucose for an oral glucose tolerance test | |
Secondary | Acetylcholine (Ach) iontophoresis | Acetylcholine (Ach) iontophoresis measure of microvascular function | Visit 2: (baseline) and 1, 2 and 3 hours following ingestion of 75 g glucose for an oral glucose tolerance test | |
Secondary | Insulin iontophoresis | Insulin iontophoresis measure of microvascular function | Visit 2: (baseline) and 1, 2 and 3 hours following ingestion of 75 g glucose for an oral glucose tolerance | |
Secondary | Glucose concentration | Glucose concentration | Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test | |
Secondary | Insulin concentration | Insulin concentration | Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test |
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