NCT01975259: IECF

Investigating the Incretin Effect in Cystic Fibrosis

Completed Last updated 1 September 2015

What this trial tests

trial testing Oral Glucose Tolerance test (75g 2-hour) in Cystic Fibrosis in 50 participants. Completed in 1 July 2015.

Timeline

1 December 2013

Primary endpoint
1 July 2015

1 July 2015

Quick facts

Lead sponsor	Liverpool Heart and Chest Hospital NHS Foundation Trust
Status	Completed
Study type	OBSERVATIONAL
Enrollment	50
Start date	1 December 2013
Primary completion	1 July 2015
Estimated completion	1 July 2015
Sites	1 location across United Kingdom

Drugs / interventions tested

• Oral Glucose Tolerance test (75g 2-hour)
• Modified Oral Glucose Tolerance Test (50g 4-hours) — full drug profile →
• Matched isoglycemic clamp — full drug profile →
• Hyperglycemic clamp with concurrent GLP-1 infusion — full drug profile →
• Hyperglycemic Clamp with concurrent GIP infusion — full drug profile →
• Hyperglycemic clamp with placebo infusion — full drug profile →
• Liquid Meal Test (Carbohydrate-rich)
• Liquid Meal Test (Fat-rich)
• Liquid Meal Test (Mixed)
• Continuous Glucose Monitoring

Conditions studied

• Cystic Fibrosis — all drugs for Cystic Fibrosis →

Sponsor

Liverpool Heart and Chest Hospital NHS Foundation Trust

Who can join

Adults 17 to 50, any sex, with Cystic Fibrosis. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.