Cystic Fibrosis (CF)NCT03234387
A CFit Study - Baseline
An observational study of Cystic Fibrosis (CF) and Cystic Fibrosis-related Diabetes, run by University of Portsmouth at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis (CF), Cystic Fibrosis-related Diabetes
- Type of treatment
- Pill or oral medicine
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Nov 2017to 1 Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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)
Who may be able to join
- 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
Show all 16Show fewer
- 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
- 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
- Age- and gender
Who cannot join
- 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:
Show all 27Show fewer
- Cystic fibrosis (CF) without established CF-related diabetes:
- 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
- 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:
- 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
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Department of Sport and Exercise Science
Portsmouth, Hampshire, PO1 2ER
About this study
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?
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.
Read the detailed description
Participants and recruitment The present study will be a pilot, cross-sectional trial in individuals with CFRD (n = 15), as well as age- and gender-matched CF controls without diabetes (n = 15) and age- and gender-matched healthy control participants (n = 15). Participants will be recruited from adult and paediatric CF outpatient clinics within the Southampton CF network. The healthy control participants will be recruited from the University of Portsmouth and local area. Individuals with CF will be tested at a laboratory established within the CF unit at the Southampton General Hospital and/or the Department of Sport and Exercise Sciences (University of Portsmouth), depending on participant convenience. All healthy control participants will attend the Department of Sport and Exercise Sciences at the University of Portsmouth.
Visit 1 During this visit, a valid informed consent and GCP trained member of the research team will fully explain the information sheet and study protocol, as well as answer any questions to ensure that all relevant parties are clear about the study requirements. Following this, fully informed written consent will be obtained. Additionally, informed written assent will be obtained from those < 16 years of age.
Following the consent procedures the participants resting pulmonary function (forced vital capacity, forced expiratory volume in 1 second, mid force expiratory flow and peak expiratory flow) and anthropometric measures (weight, height and body fat percentage) will obtained. The subsequent aim of this visit is then to habituate all participants with exercising on a cycle ergometer in preparation for their CPET in visit 2, in particular maintaining a certain cadence at a given power output. Appropriate adjustments will be made to the ergometer seat and handlebar position, and noted for visit 2. Furthermore, the protocols of obtaining ones ratings of perceived exertion and dyspnoea will be fully explained. Lastly, the participant will be instructed to avoid consuming mouthwash for the entirety of the study period due to evidence suggesting it may influence the uptake of dietary nitrate.
Visit 2 Participants will arrive to the laboratory at 1900 ± 2 hours. They will be instructed to arrive 2 hours postprandial, having avoided caffeine for > 12 hours, as well as nitrate rich foods, alcohol and exhaustive exercise for > 24 hours.
Upon arrival, CGM's will be fixed to the interior surface of the upper arm and worn for the subsequent 14 days. In addition to this, hip worn accelerometers, as well as hourly specific physical activity and food diaries will be distributed and completed for 14 days alongside the CGM. The participants resting pulmonary function will be assessed using the spirometry procedures described below, and a resting blood sample will be collected via venepuncture for the analysis of plasma [NO-(₂)] and ET-1. Additionally, the cycle ergometer CPET with a supramaximal (Smax) verification phase will be employed to determine ones aerobic exercise function, and a second venous blood sample will be collected immediately following exercise termination for the analysis of plasma [NO-(₂)] and ET-1. The total volume of blood collected over this 2 hour visit will be approximately 20 mL.
Visit 3 Participants will be required to arrive to the laboratory ≥ 3 days post visit 1, at 0800 ± 2 hours, following an overnight fast (> 10 hours). Furthermore, participants will be instructed to avoid nitrate rich foods, caffeine, alcohol and exhaustive exercise for 24 hours prior to arrival.
Upon arrival participants will undergo the acetylcholine (ACh) and insulin iontophoresis protocols described below, including 5 resting blood pressure measurements. Immediately following this, the participant's pulmonary function will be assessed via spirometry. Participants will be asked to rest, and entertainment will be provided, for the following 60 minutes. The iontophoresis procedures will then be repeated to assess the short-term test-retest variability of the iontophoresis procedures. Following this, a cannula will be inserted into a vein by a trained phlebotomist, prior to the 3 hour OGTT and a baseline blood sample will be taken (measuring all the below biomarkers). Venous blood samples will be drawn at 30, 60, 90, 120 and 180 minutes post glucose ingestion for the analysis of glucose, insulin, active glucagon-like peptide-1 (GLP-1), TNF-α, soluble vascular cell adhesion molecule-1 (sVCAM-1), IL-6, [NO-(₂)] and ET-1. NT, total glutathione (tGSH) and total cysteine (tCys) will be analysed at 120 minutes post-glucose ingestion. The total volume of blood collected over this 5 hour visit will be approximately 176 mL. Additionally, the iontophoresis procedures will be repeated at 30, 90 and 150 minutes post-glucose ingestion (i.e. hourly measurements of microvascular endothelial function).
Follow-up CGM's, accelerometers and physical activity/food diaries will be completed for 14 days following visit 1. A member of the research team will collect these from the preferred location of the participant.
- Being tested
- No intervention - only assessments.
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No intervention - only assessments.Other
Also called Exercise testing, Insulin and acetylcholine iontophoresis measures of microvascular function, Oral glucose tolerance test (75 g glucose)
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: No intervention - only assessments. | |
| Healthy controls | Age- and gender-matched healthy control participants. Receives: Other: No intervention - only assessments. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal oxygen uptake (aerobic fitness)
Maximal oxygen uptake (aerobic fitness) from a maximal cardiopulmonary exercise testing on a cycle ergometer
Measured: Visit 1 - Baseline
Secondary outcomes (20)
VO2 gain
Oxygen cost of exercise (efficiency) - derived from maximal cardiopulmonary exercise test on a cycle ergometer
Measured: Visit 1 - Baseline
VO2 mean response time
VO2 mean response time - derived from maximal cardiopulmonary exercise test
Measured: Visit 1 - Baseline
Gas exchange threshold
Gas exchange threshold - derived from maximal cardiopulmonary exercise test
Measured: Visit 1 - Baseline
Near-infrared spectroscopy derived deoxygenated [haemoglobin + myoglobin]
Dynamics of near-infrared spectroscopy derived deoxygenated [haemoglobin + myoglobin]
Measured: Visit 1 - Baseline
Pulmonary function
Pulmonary function measured using flow-volume loop spirometry
Measured: Visit 1 (baseline), Visit 2 (baseline)
Glycaemic control
Glycaemic control measured using an arm-mounted continuous glucose monitor
Measured: Glycaemic control will be measured continuously for 14 days following visit 1.
Physical activity
Physical activity measured using a wrist-mounted physical activity monitor
Measured: Physical activity will be measured continuously for 14 days following visit 1.
Dietary intake
Dietary intake measured using MyFitness Pal application and food diaries
Measured: Food diaries will be completed for 14 days following visit 1.
Tumour necrosis factor alpha (TNF-alpha)
Tumour necrosis factor alpha (TNF-alpha) measured from plasma
Measured: Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Soluble vascular cell adhesion molecule-1 (sVCAM)
Soluble vascular cell adhesion molecule-1 (sVCAM) measured from plasma
Measured: Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Endothelin-1 (ET-1)
Endothelin-1 (ET-1) measured from plasma
Measured: 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
Interleukin-6 (IL-6)
Interleukin-6 (IL-6) measured from plasma
Measured: Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
[Nitrite] (NO2)
Nitrite concentration measured from plasma
Measured: 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
Nitrotyrosine (NT)
Nitrotyrosine (NT) measured from plasma
Measured: Visit 2: (baseline) and 120 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Total glutathione (tGSH)
Total glutathione (tGSH) measured from plasma
Measured: Visit 2: (baseline) and 120 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Total cysteine (tCys)
Total cysteine (tCys) measured from plasma
Measured: Visit 2: (baseline) and 120 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Acetylcholine (Ach) iontophoresis
Acetylcholine (Ach) iontophoresis measure of microvascular function
Measured: Visit 2: (baseline) and 1, 2 and 3 hours following ingestion of 75 g glucose for an oral glucose tolerance test
Insulin iontophoresis
Insulin iontophoresis measure of microvascular function
Measured: Visit 2: (baseline) and 1, 2 and 3 hours following ingestion of 75 g glucose for an oral glucose tolerance
Glucose concentration
Glucose concentration
Measured: Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Insulin concentration
Insulin concentration
Measured: Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study start17 Nov 2017
- Primary completion1 Dec 2020
- Study completion1 Dec 2020
Why it stopped: Poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic Fibrosis (CF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Portsmouth
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Southampton NHS Foundation Trust, Loughborough University, Queen Alexandra Hospital
- Responsible party
- Principal investigator, Dr Zoe Saynor, University of Portsmouth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03234387
- Sponsor's protocol ID
- ZS002
- Status last verified
- Apr 2021
- First submitted
- 26 Jul 2017
- Last updated
- 28 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will be shared with the study team only.
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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?
- ClinicalTrials.gov ID
- NCT03234387
- Acronym / sponsor ID
- ZS002
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Poor recruitment
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of PortsmouthUniversity, hospital or other
- Collaborators
- University Hospital Southampton NHS Foundation Trust, Loughborough University, Queen Alexandra Hospital
- Study start
- 17 Nov 2017 (actual)
- Primary completion
- 1 Dec 2020 (actual)
- Study completion
- 1 Dec 2020 (actual)
- First posted
- 31 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Participants and recruitment The present study will be a pilot, cross-sectional trial in individuals with CFRD (n = 15), as well as age- and gender-matched CF controls without diabetes (n = 15) and age- and gender-matched healthy control participants (n = 15). Participants will be recruited from adult and paediatric CF outpatient clinics within the Southampton CF network. The healthy control participants will be recruited from the University of Portsmouth and local area. Individuals with CF will be tested at a laboratory established within the CF unit at the Southampton General Hospital and/or the Department of Sport and Exercise Sciences (University of Portsmouth), depending on participant convenience. All healthy control participants will attend the Department of Sport and Exercise Sciences at the University of Portsmouth.
Visit 1 During this visit, a valid informed consent and GCP trained member of the research team will fully explain the information sheet and study protocol, as well as answer any questions to ensure that all relevant parties are clear about the study requirements. Following this, fully informed written consent will be obtained. Additionally, informed written assent will be obtained from those < 16 years of age.
Following the consent procedures the participants resting pulmonary function (forced vital capacity, forced expiratory volume in 1 second, mid force expiratory flow and peak expiratory flow) and anthropometric measures (weight, height and body fat percentage) will obtained. The subsequent aim of this visit is then to habituate all participants with exercising on a cycle ergometer in preparation for their CPET in visit 2, in particular maintaining a certain cadence at a given power output. Appropriate adjustments will be made to the ergometer seat and handlebar position, and noted for visit 2. Furthermore, the protocols of obtaining ones ratings of perceived exertion and dyspnoea will be fully explained. Lastly, the participant will be instructed to avoid consuming mouthwash for the entirety of the study period due to evidence suggesting it may influence the uptake of dietary nitrate.
Visit 2 Participants will arrive to the laboratory at 1900 ± 2 hours. They will be instructed to arrive 2 hours postprandial, having avoided caffeine for > 12 hours, as well as nitrate rich foods, alcohol and exhaustive exercise for > 24 hours.
Upon arrival, CGM's will be fixed to the interior surface of the upper arm and worn for the subsequent 14 days. In addition to this, hip worn accelerometers, as well as hourly specific physical activity and food diaries will be distributed and completed for 14 days alongside the CGM. The participants resting pulmonary function will be assessed using the spirometry procedures described below, and a resting blood sample will be collected via venepuncture for the analysis of plasma [NO-(₂)] and ET-1. Additionally, the cycle ergometer CPET with a supramaximal (Smax) verification phase will be employed to determine ones aerobic exercise function, and a second venous blood sample will be collected immediately following exercise termination for the analysis of plasma [NO-(₂)] and ET-1. The total volume of blood collected over this 2 hour visit will be approximately 20 mL.
Visit 3 Participants will be required to arrive to the laboratory ≥ 3 days post visit 1, at 0800 ± 2 hours, following an overnight fast (> 10 hours). Furthermore, participants will be instructed to avoid nitrate rich foods, caffeine, alcohol and exhaustive exercise for 24 hours prior to arrival.
Upon arrival participants will undergo the acetylcholine (ACh) and insulin iontophoresis protocols described below, including 5 resting blood pressure measurements. Immediately following this, the participant's pulmonary function will be assessed via spirometry. Participants will be asked to rest, and entertainment will be provided, for the following 60 minutes. The iontophoresis procedures will then be repeated to assess the short-term test-retest variability of the iontophoresis procedures. Following this, a cannula will be inserted into a vein by a trained phlebotomist, prior to the 3 hour OGTT and a baseline blood sample will be taken (measuring all the below biomarkers). Venous blood samples will be drawn at 30, 60, 90, 120 and 180 minutes post glucose ingestion for the analysis of glucose, insulin, active glucagon-like peptide-1 (GLP-1), TNF-α, soluble vascular cell adhesion molecule-1 (sVCAM-1), IL-6, [NO-(₂)] and ET-1. NT, total glutathione (tGSH) and total cysteine (tCys) will be analysed at 120 minutes post-glucose ingestion. The total volume of blood collected over this 5 hour visit will be approximately 176 mL. Additionally, the iontophoresis procedures will be repeated at 30, 90 and 150 minutes post-glucose ingestion (i.e. hourly measurements of microvascular endothelial function).
Follow-up CGM's, accelerometers and physical activity/food diaries will be completed for 14 days following visit 1. A member of the research team will collect these from the preferred location of the participant.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cystic fibrosis (CF) with established CF-related diabetes | – | Other: No intervention - only assessments.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 |
| Cystic fibrosis (CF) without established CF-related diabetes | – | Other: No intervention - only assessments.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 |
| Healthy controls | – | Other: No intervention - only assessments.Age- and gender-matched healthy control participants. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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)
Key inclusion criteria (16 listed)
- 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:
- No contraindications to performing exhaustive exercise
- Can understand and cooperate with the study protocol
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No intervention - only assessments.Also: Exercise testing, Insulin and acetylcholine iontophoresis measures of microvascular function, Oral glucose tolerance test (75 g glucose)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. | Other | Cystic fibrosis (CF) with established CF-related diabetes, Cystic fibrosis (CF) without established CF-related diabetes, Healthy controls |
Primary outcome
Maximal oxygen uptake (aerobic fitness)
Time frame: Visit 1 - Baseline
Maximal oxygen uptake (aerobic fitness) from a maximal cardiopulmonary exercise testing on a cycle ergometer
20 secondary outcomes
VO2 gain
Time frame: Visit 1 - Baseline
VO2 mean response time
Time frame: Visit 1 - Baseline
Gas exchange threshold
Time frame: Visit 1 - Baseline
Near-infrared spectroscopy derived deoxygenated [haemoglobin + myoglobin]
Time frame: Visit 1 - Baseline
Pulmonary function
Time frame: Visit 1 (baseline), Visit 2 (baseline)
Glycaemic control
Time frame: Glycaemic control will be measured continuously for 14 days following visit 1.
Physical activity
Time frame: Physical activity will be measured continuously for 14 days following visit 1.
Dietary intake
Time frame: Food diaries will be completed for 14 days following visit 1.
Tumour necrosis factor alpha (TNF-alpha)
Time frame: Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Soluble vascular cell adhesion molecule-1 (sVCAM)
Time frame: Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Endothelin-1 (ET-1)
Time frame: 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
Interleukin-6 (IL-6)
Time frame: Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
[Nitrite] (NO2)
Time frame: 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
Nitrotyrosine (NT)
Time frame: Visit 2: (baseline) and 120 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Total glutathione (tGSH)
Time frame: Visit 2: (baseline) and 120 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Total cysteine (tCys)
Time frame: Visit 2: (baseline) and 120 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Acetylcholine (Ach) iontophoresis
Time frame: Visit 2: (baseline) and 1, 2 and 3 hours following ingestion of 75 g glucose for an oral glucose tolerance test
Insulin iontophoresis
Time frame: Visit 2: (baseline) and 1, 2 and 3 hours following ingestion of 75 g glucose for an oral glucose tolerance
Glucose concentration
Time frame: Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Insulin concentration
Time frame: Visit 2: (baseline) and 30, 60, 90, 120 and 180 minutes following ingestion of 75 g glucose for an oral glucose tolerance test
Results and safety
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2021.
- Individual participant dataSharing planned: No. Data will be shared with the study team only.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis (CF) and Cystic Fibrosis-related Diabetes, run by University of Portsmouth at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal oxygen uptake (aerobic fitness) (time frame: Visit 1 - Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2021.