Cystic FibrosisIECFNCT01975259
Investigating the Incretin Effect in Cystic Fibrosis
An observational study of Cystic Fibrosis, run by Liverpool Heart and Chest Hospital NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Most Cystic fibrosis (CF) patients now commonly live well into adulthood, this means they are progressively accumulating damage to the insulin-secreting cells inside their pancreas. This explains why most adult patients have some degree of abnormal sugar regulation \& rates of diabetes rise significantly with age. Read more about this study
- Who is it for?
- Ages 17 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Oral Glucose Tolerance test (75g 2-hour), Modified Oral Glucose Tolerance Test (50g 4-hours) and Matched isoglycemic clamp
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2013to Jul 2015
- 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 17 to 50 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: The CF Cohort will be recruited from the population of Patients attending Adult CF Service at Liverpool Heart \& Chest Hospital, Liverpool, United Kingdom The control group will be invited to participate from the general public. We will advertise our study through the Liverpool Heart \& Chest Hospital and also via GP surgeries (Primary care clinics) in both electronic \& paper forms.
Who may be able to join
- Cystic fibrosis as diagnosed by EITHER Cystic fibrosis transmembrane conductance regulator (CFTR) mutation on genotyping OR Positive sweat test (Chloride ≥60mmol/L after pilocarpine iontophoresis) AND Clinical features in keeping with a diagnosis of Cystic Fibrosis
- Clinically stable for at least 4 weeks without inpatient or outpatient treatment for an infective exacerbation - including antibiotics (other than long-term prophylactic therapy) or steroids
Who cannot join
- Active Pregnancy or <12 months Post-partum
- Clinically unstable patients
- Patients on long-term steroids
- Patients with known gastroparesis or previous surgery to the gastrointestinal tract (including vagotomy)
- History of organ transplant or planned organ transplant awaited
- Non-CF related diabetes (e.g. Type 1 or 2 Diabetes Mellitus)
Show all 11Show fewer
- Active malignancy
- Clinically significant derangements in haematological or biochemical indices
- Clinical symptoms of malabsorption (frequent bowel motions/passing of undigested foodstuffs or steatorrhoea)
- Known difficult venous access
- Use of bile acid sequestrants in the previous 4 weeks
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Liverpool Heart and Chest Hospital
Liverpool, L14 3PE
About this study
Most Cystic fibrosis (CF) patients now commonly live well into adulthood, this means they are progressively accumulating damage to the insulin-secreting cells inside their pancreas. This explains why most adult patients have some degree of abnormal sugar regulation \& rates of diabetes rise significantly with age. CF related diabetes is categorically different from other types of diabetes \& its development is serious as it heralds a faster decline in lung function \& a reduced life expectancy.
The hallmark of abnormal sugar handling in CF is high glucose levels after meals as the damaged pancreas responds abnormally slowly. Over 70% of the initial response of a healthy pancreas is induced, not by glucose alone, but by hormones released from the bowel known as incretins. We want to establish whether incretins are important in blood sugar handling in CF as specific drugs that enhance their effect are now available.
The study hypothesis is that the incretin system will function normally in patients with Cystic Fibrosis. To show this we will measure how much insulin secretion is dependant on incretin hormones in CF patients by comparing levels after a sugary drink test and then an intravenous glucose drip test (run at a rate that mimics the blood sugar levels obtained during the first test to make it a fair comparison ) - as incretins will only be produced in the first test when the sugar passes through the bowel any extra insulin produced will be due to these hormones. To detect resistance to the incretin hormones we will separately measure responses to direct infusions of the hormones themselves. We will explore which components of meals cause incretin hormone release from the bowel wall by measuring blood levels after different types of meals are consumed. Finally we will measure levels of the enzyme that breaks down the incretin hormones (DPP-4) to know if they are deactivated more quickly in people with CF. By describing the incretin system in CF we will considerably improve our understanding of this important condition as well as potentially highlighting new ways to treat it.
- Conditions
- Cystic Fibrosis
- Being tested
- Oral Glucose Tolerance test (75g 2-hour), Modified Oral Glucose Tolerance Test (50g 4-hours), Matched isoglycemic clamp, Hyperglycemic clamp with concurrent GLP-1 infusion, Hyperglycemic Clamp with concurrent GIP infusion
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Glucose Tolerance test (75g 2-hour)Drug
Also called OGTT
A standard 2-hour oral glucose tolerance test where fasted patients (10hours overnight) consume a 75g glucose solution \& have glucose levels recorded up to every 30 mins for 2hours
Modified Oral Glucose Tolerance Test (50g 4-hours)Drug
Also called Modified OGTT, 50g OGTT
A 4-hour version of the oral glucose tolerance test where fasted patients (10hours overnight) consume a 50g of glucose solution \& have glucose levels recorded up to every 5mins as well pancreatic and incretin responses at 10 fixed time points.
Matched isoglycemic clampDrug
Also called isoglycemic clamp
A glucose drip will be infused at a variable rate that recreates the individual subjects blood glucose values obtained during their 4-hour modified oral glucose tolerance test. This test will therefore last 4-hours and again subjects will be fasted (10hours overnight) at the time of the test. The same blood tests will be performed at the same time points as the modified glucose tolerance test
Hyperglycemic clamp with concurrent GLP-1 infusionDrug
Also called Glucagon-like peptide-1
An intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp). After 60mins an infusion of GLP-1 will be commenced at a rate of 0.25pmol/kg/min for 60mins and then continued at a rate of 1.2pmol/kg/min for a further 60mins. Subjects will be blinded to what infusion they are receiving.
Hyperglycemic Clamp with concurrent GIP infusionDrug
Also called gastric inhibitory polypeptide, glucose-dependent insulinotropic peptide
An intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp). After 60mins an infusion of GIP will be commenced at a rate of 1pmol/kg/min for 60mins and then continued at a rate of 4pmol/kg/min for a further 60mins. Subjects will be blinded to what infusion they are receiving.
Hyperglycemic clamp with placebo infusionDrug
Also called Hyperglycemic clamp with normal saline (0.9%) infusion
An intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp).
After 60mins an infusion of normal saline will be commenced as a placebo infusion. It will be infused at a rate so that the total volume of fluid is similar to that infused during the other two hyperglycemic clamp interventions. Subjects will be blinded to what infusion they are receiving.
Liquid Meal Test (Carbohydrate-rich)Other
A standardised liquid meal (carbohydrate-rich) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal.
Liquid Meal Test (Fat-rich)Other
A standardised liquid meal (fat-rich) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal.
Liquid Meal Test (Mixed)Other
A standardised liquid meal (mixed) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal.
Continuous Glucose MonitoringDevice
Also called CGM, CGMS
Continuous glucose monitoring entails wearing a small portable device, usually on the upper arm, for a period of three days. The device uses a small plastic tube to record the glucose level from interstitial fluid \& every minute wirelessly transmits this information to a base unit to enable a very accurate estimate of average blood sugar control to be defined.
| Study group | Role | What they receive |
|---|---|---|
| Cystic Fibrosis | Adult patients with confirmed cystic fibrosis who are clinically stable. Interventions:
Oral Glucose Tolerance test (75g 2-hour) Modified Oral Glucose Tolerance Test (50g 4-hours) Matched isoglycemic clamp Hyperglycemic clamp with concurrent GLP-1 infusion Hyperglycemic Clamp with concurrent GIP infusion Hyperglycemic clamp with placebo infusion Liquid Meal Test (Carbohydrate-rich) Continuous Glucose Monitoring Receives: Drug: Oral Glucose Tolerance test (75g 2-hour); Drug: Modified Oral Glucose Tolerance Test (50g 4-hours); Drug: Matched isoglycemic clamp; Drug: Hyperglycemic clamp with concurrent GLP-1 infusion; Drug: Hyperglycemic Clamp with concurrent GIP infusion; Drug: Hyperglycemic clamp with placebo infusion; Other: Liquid Meal Test (Carbohydrate-rich); Other: Liquid Meal Test (Fat-rich); Other: Liquid Meal Test (Mixed); Device: Continuous Glucose Monitoring | |
| Controls | Adult Non-CF subjects matched for age and body mass index with normal glucose tolerance.
Oral Glucose Tolerance test (75g 2-hour) Modified Oral Glucose Tolerance Test (50g 4-hours) Matched isoglycemic clamp Hyperglycemic clamp with concurrent GLP-1 infusion Hyperglycemic Clamp with concurrent GIP infusion Hyperglycemic clamp with placebo infusion Liquid Meal Test (Carbohydrate-rich) Receives: Drug: Oral Glucose Tolerance test (75g 2-hour); Drug: Modified Oral Glucose Tolerance Test (50g 4-hours); Drug: Matched isoglycemic clamp; Drug: Hyperglycemic clamp with concurrent GLP-1 infusion; Drug: Hyperglycemic Clamp with concurrent GIP infusion; Drug: Hyperglycemic clamp with placebo infusion; Other: Liquid Meal Test (Carbohydrate-rich); Other: Liquid Meal Test (Fat-rich); Other: Liquid Meal Test (Mixed) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under Curve (AUC) of Insulin & C-peptide secretion during a matched isoglycemic clamp
Differences in Insulin \& C-peptide secretion will be measured over a 4-hour period following an oral glucose tolerance test and then separately over the same period during a matched isoglycemic glucose infusion (which will recreate the glucose values obtained during the oral glucose tolerance test). The difference in these values can be wholly attributed to the effect of incretin hormones.
Measured: 4 hours
Volume of intravenous glucose required to maintain a hyperglycemic clamp at 180-216mg/dL
A hyperglycemic clamp uses an intravenous glucose infusion to fix blood sugar at a certain level. We will use such a technique to fix blood sugar levels at 180-216mg/dL (10-12 mmol/l) for one hour then infuse either an incretin hormone (GLP-1/GIP) or placebo (sodium chloride) for a further two hours. The excess volume of intravenous glucose required during the last two hours of the test (compared to the first) will allow us to calculate what if any effect the incretin hormones have on the pancreas in patients with Cystic Fibrosis
Measured: 3 hours
Secondary outcomes (2)
Serum DPP-4 levels
We will measure serum DPP-4 levels on 2 separate occasions in both CF and control groups to establish if there are any differences in how rapidly the incretin hormones are deactivated between the groups
Measured: 0 mins
AUC incretin hormone levels (GLP-1/GIP)
Incretin hormone levels (GLP-1/GIP) will be measured in response to an oral glucose tolerance test, an intravenous isoglycemic glucose infusion as well as in response to standardised meals of different composition (fat-rich, carbohydrate rich \& mixed).
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2013 (estimated)
- Study startDec 2013
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liverpool Heart and Chest Hospital NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gareth H Jones, MBChB, Principal investigator, Liverpool Heart and Chest Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01975259
- Sponsor's protocol ID
- 1004
- Other IDs
- 2013-003758-26
- Acronym
- IECF
- Status last verified
- Sep 2015
- First submitted
- 11 Sep 2013
- Last updated
- 2 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986 Jan;29(1):46-52. doi: 10.1007/BF02427280.
PubMed 3514343Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993 Jan;91(1):301-7. doi: 10.1172/JCI116186.
PubMed 8423228Mohan K, Miller H, Dyce P, Grainger R, Hughes R, Vora J, Ledson M, Walshaw M. Mechanisms of glucose intolerance in cystic fibrosis. Diabet Med. 2009 Jun;26(6):582-8. doi: 10.1111/j.1464-5491.2009.02738.x.
PubMed 19538232Milla CE, Warwick WJ, Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):891-5. doi: 10.1164/ajrccm.162.3.9904075.
PubMed 10988101Hameed S, Morton JR, Jaffe A, Field PI, Belessis Y, Yoong T, Katz T, Verge CF. Early glucose abnormalities in cystic fibrosis are preceded by poor weight gain. Diabetes Care. 2010 Feb;33(2):221-6. doi: 10.2337/dc09-1492. Epub 2009 Nov 12.
PubMed 19910502Dobson L, Sheldon CD, Hattersley AT. Validation of interstitial fluid continuous glucose monitoring in cystic fibrosis. Diabetes Care. 2003 Jun;26(6):1940-1. doi: 10.2337/diacare.26.6.1940-a. No abstract available.
PubMed 12766139Costa M, Potvin S, Hammana I, Malet A, Berthiaume Y, Jeanneret A, Lavoie A, Levesque R, Perrier J, Poisson D, Karelis AD, Chiasson JL, Rabasa-Lhoret R. Increased glucose excursion in cystic fibrosis and its association with a worse clinical status. J Cyst Fibros. 2007 Nov 30;6(6):376-83. doi: 10.1016/j.jcf.2007.02.005. Epub 2007 Apr 3.
PubMed 17409029Hillman M, Eriksson L, Mared L, Helgesson K, Landin-Olsson M. Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus. J Cyst Fibros. 2012 Mar;11(2):144-9. doi: 10.1016/j.jcf.2011.11.001. Epub 2011 Dec 3.
PubMed 22138561Anzeneder L, Kircher F, Feghelm N, Fischer R, Seissler J. Kinetics of insulin secretion and glucose intolerance in adult patients with cystic fibrosis. Horm Metab Res. 2011 May;43(5):355-60. doi: 10.1055/s-0031-1275270. Epub 2011 Mar 29.
PubMed 21448848Lanng S, Thorsteinsson B, Roder ME, Orskov C, Holst JJ, Nerup J, Koch C. Pancreas and gut hormone responses to oral glucose and intravenous glucagon in cystic fibrosis patients with normal, impaired, and diabetic glucose tolerance. Acta Endocrinol (Copenh). 1993 Mar;128(3):207-14. doi: 10.1530/acta.0.1280207.
PubMed 8480468
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Incretin Effect in Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT01975259
- Acronym / sponsor ID
- IECF / 1004
- Conditions
- Cystic Fibrosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Liverpool Heart and Chest Hospital NHS Foundation TrustUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 4 Nov 2013 (estimated)
- 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.
Most Cystic fibrosis (CF) patients now commonly live well into adulthood, this means they are progressively accumulating damage to the insulin-secreting cells inside their pancreas. This explains why most adult patients have some degree of abnormal sugar regulation \& rates of diabetes rise significantly with age. CF related diabetes is categorically different from other types of diabetes \& its development is serious as it heralds a faster decline in lung function \& a reduced life expectancy.
The hallmark of abnormal sugar handling in CF is high glucose levels after meals as the damaged pancreas responds abnormally slowly. Over 70% of the initial response of a healthy pancreas is induced, not by glucose alone, but by hormones released from the bowel known as incretins. We want to establish whether incretins are important in blood sugar handling in CF as specific drugs that enhance their effect are now available.
The study hypothesis is that the incretin system will function normally in patients with Cystic Fibrosis. To show this we will measure how much insulin secretion is dependant on incretin hormones in CF patients by comparing levels after a sugary drink test and then an intravenous glucose drip test (run at a rate that mimics the blood sugar levels obtained during the first test to make it a fair comparison ) - as incretins will only be produced in the first test when the sugar passes through the bowel any extra insulin produced will be due to these hormones. To detect resistance to the incretin hormones we will separately measure responses to direct infusions of the hormones themselves. We will explore which components of meals cause incretin hormone release from the bowel wall by measuring blood levels after different types of meals are consumed. Finally we will measure levels of the enzyme that breaks down the incretin hormones (DPP-4) to know if they are deactivated more quickly in people with CF. By describing the incretin system in CF we will considerably improve our understanding of this important condition as well as potentially highlighting new ways to treat it.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cystic Fibrosis | – | Drug: Oral Glucose Tolerance test (75g 2-hour), Drug: Modified Oral Glucose Tolerance Test (50g 4-hours), Drug: Matched isoglycemic clamp, Drug: Hyperglycemic clamp with concurrent GLP-1 infusion, Drug: Hyperglycemic Clamp with concurrent GIP infusion, Drug: Hyperglycemic clamp with placebo infusion, Other: Liquid Meal Test (Carbohydrate-rich), Other: Liquid Meal Test (Fat-rich), Other: Liquid Meal Test (Mixed), Device: Continuous Glucose MonitoringAdult patients with confirmed cystic fibrosis who are clinically stable. Interventions: Oral Glucose Tolerance test (75g 2-hour) Modified Oral Glucose Tolerance Test (50g 4-hours) Matched isoglycemic clamp Hyperglycemic clamp with concurrent GLP-1 infusion Hyperglycemic Clamp with concurrent GIP infusion Hyperglycemic clamp with placebo infusion Liquid Meal Test (Carbohydrate-rich) Continuous Glucose Monitoring |
| Controls | – | Drug: Oral Glucose Tolerance test (75g 2-hour), Drug: Modified Oral Glucose Tolerance Test (50g 4-hours), Drug: Matched isoglycemic clamp, Drug: Hyperglycemic clamp with concurrent GLP-1 infusion, Drug: Hyperglycemic Clamp with concurrent GIP infusion, Drug: Hyperglycemic clamp with placebo infusion, Other: Liquid Meal Test (Carbohydrate-rich), Other: Liquid Meal Test (Fat-rich), Other: Liquid Meal Test (Mixed)Adult Non-CF subjects matched for age and body mass index with normal glucose tolerance. Oral Glucose Tolerance test (75g 2-hour) Modified Oral Glucose Tolerance Test (50g 4-hours) Matched isoglycemic clamp Hyperglycemic clamp with concurrent GLP-1 infusion Hyperglycemic Clamp with concurrent GIP infusion Hyperglycemic clamp with placebo infusion Liquid Meal Test (Carbohydrate-rich) |
Who may qualify
- Ages
- 17 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- The CF Cohort will be recruited from the population of Patients attending Adult CF Service at Liverpool Heart \& Chest Hospital, Liverpool, United Kingdom The control group will be invited to participate from the general public. We will advertise our study through the Liverpool Heart \& Chest Hospital and also via GP surgeries (Primary care clinics) in both electronic \& paper forms.
Key inclusion criteria (2 listed)
- Cystic fibrosis as diagnosed by EITHER Cystic fibrosis transmembrane conductance regulator (CFTR) mutation on genotyping OR Positive sweat test (Chloride ≥60mmol/L after pilocarpine iontophoresis) AND Clinical features in keeping with a diagnosis of Cystic Fibrosis
- Clinically stable for at least 4 weeks without inpatient or outpatient treatment for an infective exacerbation - including antibiotics (other than long-term prophylactic therapy) or steroids
Key exclusion criteria (11 listed)
- Active Pregnancy or <12 months Post-partum
- Clinically unstable patients
- Patients on long-term steroids
- Patients with known gastroparesis or previous surgery to the gastrointestinal tract (including vagotomy)
- History of organ transplant or planned organ transplant awaited
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 |
|---|---|---|
| Oral Glucose Tolerance test (75g 2-hour)Also: OGTTA standard 2-hour oral glucose tolerance test where fasted patients (10hours overnight) consume a 75g glucose solution \& have glucose levels recorded up to every 30 mins for 2hours | Drug | Controls, Cystic Fibrosis |
| Modified Oral Glucose Tolerance Test (50g 4-hours)Also: Modified OGTT, 50g OGTTA 4-hour version of the oral glucose tolerance test where fasted patients (10hours overnight) consume a 50g of glucose solution \& have glucose levels recorded up to every 5mins as well pancreatic and incretin responses at 10 fixed time points. | Drug | Controls, Cystic Fibrosis |
| Matched isoglycemic clampAlso: isoglycemic clampA glucose drip will be infused at a variable rate that recreates the individual subjects blood glucose values obtained during their 4-hour modified oral glucose tolerance test. This test will therefore last 4-hours and again subjects will be fasted (10hours overnight) at the time of the test. The same blood tests will be performed at the same time points as the modified glucose tolerance test | Drug | Controls, Cystic Fibrosis |
| Hyperglycemic clamp with concurrent GLP-1 infusionAlso: Glucagon-like peptide-1An intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp). After 60mins an infusion of GLP-1 will be commenced at a rate of 0.25pmol/kg/min for 60mins and then continued at a rate of 1.2pmol/kg/min for a further 60mins. Subjects will be blinded to what infusion they are receiving. | Drug | Controls, Cystic Fibrosis |
| Hyperglycemic Clamp with concurrent GIP infusionAlso: gastric inhibitory polypeptide, glucose-dependent insulinotropic peptideAn intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp). After 60mins an infusion of GIP will be commenced at a rate of 1pmol/kg/min for 60mins and then continued at a rate of 4pmol/kg/min for a further 60mins. Subjects will be blinded to what infusion they are receiving. | Drug | Controls, Cystic Fibrosis |
| Hyperglycemic clamp with placebo infusionAlso: Hyperglycemic clamp with normal saline (0.9%) infusionAn intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp). After 60mins an infusion of normal saline will be commenced as a placebo infusion. It will be infused at a rate so that the total volume of fluid is similar to that infused during the other two hyperglycemic clamp interventions. Subjects will be blinded to what infusion they are receiving. | Drug | Controls, Cystic Fibrosis |
| Liquid Meal Test (Carbohydrate-rich)A standardised liquid meal (carbohydrate-rich) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal. | Other | Controls, Cystic Fibrosis |
| Liquid Meal Test (Fat-rich)A standardised liquid meal (fat-rich) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal. | Other | Controls, Cystic Fibrosis |
| Liquid Meal Test (Mixed)A standardised liquid meal (mixed) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal. | Other | Controls, Cystic Fibrosis |
| Continuous Glucose MonitoringAlso: CGM, CGMSContinuous glucose monitoring entails wearing a small portable device, usually on the upper arm, for a period of three days. The device uses a small plastic tube to record the glucose level from interstitial fluid \& every minute wirelessly transmits this information to a base unit to enable a very accurate estimate of average blood sugar control to be defined. | Device | Cystic Fibrosis |
Primary outcome
Area Under Curve (AUC) of Insulin & C-peptide secretion during a matched isoglycemic clamp
Time frame: 4 hours
Differences in Insulin \& C-peptide secretion will be measured over a 4-hour period following an oral glucose tolerance test and then separately over the same period during a matched isoglycemic glucose infusion (which will recreate the glucose values obtained during the oral glucose tolerance test). The difference in these values can be wholly attributed to the effect of incretin hormones.
Volume of intravenous glucose required to maintain a hyperglycemic clamp at 180-216mg/dL
Time frame: 3 hours
A hyperglycemic clamp uses an intravenous glucose infusion to fix blood sugar at a certain level. We will use such a technique to fix blood sugar levels at 180-216mg/dL (10-12 mmol/l) for one hour then infuse either an incretin hormone (GLP-1/GIP) or placebo (sodium chloride) for a further two hours. The excess volume of intravenous glucose required during the last two hours of the test (compared to the first) will allow us to calculate what if any effect the incretin hormones have on the pancreas in patients with Cystic Fibrosis
2 secondary outcomes
Serum DPP-4 levels
Time frame: 0 mins
AUC incretin hormone levels (GLP-1/GIP)
Time frame: 4 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2015.
- Background: PubMed 3514343Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986 Jan;29(1):46-52. doi: 10.1007/BF02427280.
- Background: PubMed 8423228Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993 Jan;91(1):301-7. doi: 10.1172/JCI116186.
- Background: PubMed 19538232Mohan K, Miller H, Dyce P, Grainger R, Hughes R, Vora J, Ledson M, Walshaw M. Mechanisms of glucose intolerance in cystic fibrosis. Diabet Med. 2009 Jun;26(6):582-8. doi: 10.1111/j.1464-5491.2009.02738.x.
- Background: PubMed 10988101Milla CE, Warwick WJ, Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):891-5. doi: 10.1164/ajrccm.162.3.9904075.
- Background: PubMed 19910502Hameed S, Morton JR, Jaffe A, Field PI, Belessis Y, Yoong T, Katz T, Verge CF. Early glucose abnormalities in cystic fibrosis are preceded by poor weight gain. Diabetes Care. 2010 Feb;33(2):221-6. doi: 10.2337/dc09-1492. Epub 2009 Nov 12.
- Background: PubMed 12766139Dobson L, Sheldon CD, Hattersley AT. Validation of interstitial fluid continuous glucose monitoring in cystic fibrosis. Diabetes Care. 2003 Jun;26(6):1940-1. doi: 10.2337/diacare.26.6.1940-a. No abstract available.
- Background: PubMed 17409029Costa M, Potvin S, Hammana I, Malet A, Berthiaume Y, Jeanneret A, Lavoie A, Levesque R, Perrier J, Poisson D, Karelis AD, Chiasson JL, Rabasa-Lhoret R. Increased glucose excursion in cystic fibrosis and its association with a worse clinical status. J Cyst Fibros. 2007 Nov 30;6(6):376-83. doi: 10.1016/j.jcf.2007.02.005. Epub 2007 Apr 3.
- Background: PubMed 22138561Hillman M, Eriksson L, Mared L, Helgesson K, Landin-Olsson M. Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus. J Cyst Fibros. 2012 Mar;11(2):144-9. doi: 10.1016/j.jcf.2011.11.001. Epub 2011 Dec 3.
- Background: PubMed 21448848Anzeneder L, Kircher F, Feghelm N, Fischer R, Seissler J. Kinetics of insulin secretion and glucose intolerance in adult patients with cystic fibrosis. Horm Metab Res. 2011 May;43(5):355-60. doi: 10.1055/s-0031-1275270. Epub 2011 Mar 29.
- Background: PubMed 8480468Lanng S, Thorsteinsson B, Roder ME, Orskov C, Holst JJ, Nerup J, Koch C. Pancreas and gut hormone responses to oral glucose and intravenous glucagon in cystic fibrosis patients with normal, impaired, and diabetic glucose tolerance. Acta Endocrinol (Copenh). 1993 Mar;128(3):207-14. doi: 10.1530/acta.0.1280207.
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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.
Gareth H Jones, MBChB principal investigator
Liverpool Heart and Chest Hospital
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, run by Liverpool Heart and Chest Hospital NHS Foundation Trust 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 2 inclusion and 11 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: finished, as of the sponsor's last update on 2 Sep 2015. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Area Under Curve (AUC) of Insulin & C-peptide secretion during a matched isoglycemic clamp (time frame: 4 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01975259, which also lists 10 linked publications.
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 2 Sep 2015.