Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000618853
Ethics application status
Approved
Date submitted
5/06/2012
Date registered
8/06/2012
Date last updated
10/04/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Do blood glucose levels after meals relate to gut hormones and stomach emptying in young people with cystic fibrosis?
Scientific title
Incretin release, gastric emptying, postprandial glycaemia in cystic fibrosis with and without enzyme supplementation.
Secondary ID [1] 280614 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 286626 0
Cystic fibrosis related diabetes 286658 0
Condition category
Condition code
Metabolic and Endocrine 286906 286906 0 0
Diabetes
Human Genetics and Inherited Disorders 286932 286932 0 0
Cystic fibrosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
CF subjects will have 2 study days on which they will consume a high fat/ carbohydrate pancake at approximately 8.30am after fasting from both solids and liquids from 10pm the previous evening. The study days will be separated by at least 24 hours so no residual 13C Na-octanoate is present at the time of the second study.

The pancake in the CF group will either be: (1) with pancreatic enzymes [1 generic capsule filled with 50,000U lipase] or (2) placebo without pancreatic enzyme replacement [1 generic capsule filled with microcellulose prepared by the pharmacy].

Pancreatic enzyme replacement
In the CF group the enzyme replacement will be double blinded and the order of the studies (one with and one without enzyme replacement) will be randomised. The capsules will be given by a medication cup so that any difference in weight and feel can’t be distinguished. Creon Forte/placebo capsules will be provided on the day of the study and will be taken at the start of the meal by the CF subjects.

Insulin administration
CF subjects who are normally on insulin will administer their ultrashort insulin analog (novorapid) before the ingestion of the meal at time -15minutes, via subcutaneous injection or an insulin pump.

Pancake
Each subject will consume the pancake within 5min. t = 0 is defined as the time of meal completion. The standard pancake (70g of Green’s (Trademark) Pancake and Pikelet Mix mixed with 100mL water and cooked with 10g butter; total of 13.5 g fat, 44.2g of carbohydrate, 252 Calories) will be modified to increase the fat content to 40g by replacing some of the H2O with polyunsaturated oil. This represents the high fat diet prescribed to CF subjects and will maximize the effect of pancreatic enzymes.

After consuming the pancake CF subjects will undergo a gastric emptying breath test and measurement of incretin hormones over 4 hours.
Intervention code [1] 285011 0
Treatment: Other
Comparator / control treatment
Subjects with cystic fibrosis act as own control (with placebo microcellulose capusules and pancreatic enzyme capsules) and are also matched to healthy controls who take no enzymes/placebo
Control group
Placebo

Outcomes
Primary outcome [1] 287263 0
Evaluate the relationship of postprandial glycaemia with gastric emptying and incretin response in young people with cystic fibrosis

Assessments:
Gastric Empyting:
13C labelled Na-octanoate (100mg) will be added to each pancake. Samples will be analysed for 13CO2 using an isotope ratio mass spectrometer. 13CO2 excretion rate will be used to calculate gastric emptying using a non-linear regression model as co -investigators have described.

Blood samples: Incretin hormones/insulin/glucagon/glucose
Blood glucose concentration will be measured immediately using a glucometer (Medisense Companion 2), and the remainder of the sample will be placed in EDTA tubes containing aprotinin on ice. Plasma will be separated and samples stored at -70 degrees C for subsequent analysis of plasma insulin, glucagon, GLP-1, and GIP using established assays at Royal Adelaide Hospital.
Timepoint [1] 287263 0
times = -15, -5, 15, 30, 45, 60, 90, 120, 150, 180, 240 min
Secondary outcome [1] 297782 0
Quantify the impact of pancreatic enzyme replacement on gastric emptying, incretin response and postprandial glycaemia in subjects with CF.

Tools:

Gastric Empyting:
13C labelled Na-octanoate (100mg) will be added to each pancake. Samples will be analysed for 13CO2 using an isotope ratio mass spectrometer. 13CO2 excretion rate will be used to calculate gastric emptying using a non-linear regression model as co -investigators have described.

Blood samples: Incretin hormones/insulin/glucagon/glucose.
Blood glucose concentration will be measured immediately using a glucometer (Medisense Companion 2), and the remainder of the sample will be placed in EDTA tubes containing aprotinin on ice. Plasma will be separated and samples stored at -70 degrees C for subsequent analysis of plasma insulin, glucagon, GLP-1, and GIP using established assays at Royal Adelaide Hospital.
Timepoint [1] 297782 0
times = -15, -5, 15, 30, 45, 60, 90, 120, 150, 180, 240 min

Eligibility
Key inclusion criteria
16 subjects with cystic fibrosis (CF) with exocrine pancreatic insufficiency and taking pancreatic enzymes. CF related diabetes will be defined as those with diabetes detected on an oral glucose tolerance test (WHO definition); CF without diabetes will be defined as those with a normal glucose tolerance test in the previous 12 months.

16 healthy control subjects without clinically significant systemic disease, and BMI <95th centile will be recruited and will be matched for age to the CF subjects.
Minimum age
10 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria CF subjects: severe pulmonary disease (FEV1<30% predicted), significant liver disease (Child-Pugh score >6), previous gastrointestinal surgery (apart from uncomplicated appendicectomy), requirement for medications that could affect gastrointestinal motility (eg erythromycin, SSRIs), pregnancy or lactation

Exclusion criteria controls: previous gastrointestinal surgery (apart from uncomplicated appendicectomy), requirement for medications that could affect gastrointestinal motility (eg erythromycin, SSRIs), pregnancy or lactation.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment.
Once enrolled subject's with cystic fibrosis and the study investigator will be blinded as to which day they take the pancreatic enzymes and which day is the placebo.
Enzymes have been put into generic capules to look the same as the placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of enzyme vs placebo day has been done by the Royal Adelaide Hospital Pharmacy using computer generated randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Study A: crossover with controls
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/06/2012
Actual
6/08/2012
Date of last participant enrolment
Anticipated
Actual
12/12/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 285373 0
Charities/Societies/Foundations
Name [1] 285373 0
McLeod Foundation
Country [1] 285373 0
Australia
Primary sponsor type
University
Name
Adelaide University
Address
Adelaide Graduation Centre
The University of Adelaide
Level 6
115 Grenfell Street
South Australia
Adelaide 5000
Country
Australia
Secondary sponsor category [1] 284232 0
Hospital
Name [1] 284232 0
Womens and Childrens Hospital
Address [1] 284232 0
72 King William Road
North Adelaide 5006
SA
Country [1] 284232 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287390 0
Womens and Children's Hospital Research Ethics Committee
Ethics committee address [1] 287390 0
72 King William Road
North Adelaide 5006
South Australia
Ethics committee country [1] 287390 0
Australia
Date submitted for ethics approval [1] 287390 0
Approval date [1] 287390 0
17/06/2012
Ethics approval number [1] 287390 0
2450

Summary
Brief summary
Gut emptying is of central importance to blood glucose levels after meals and is a major determinant of overall blood glucose control in diabetes. Blood glucose levels and insulin release after meals are also influenced by secretion of hormones from the gut in response to a meal. The gut hormones stimulate insulin secretion in response to raised blood glucose levels. However fat, rather than carbohydrate may be the most potent stimulus for gut hormone release.

We aim to measure the effect of gut emptying and gut hormone release on high blood glucose levels in youth with cystic fibrosis (CF). We will determine whether the adequate replacement of pancreatic enzymes improves blood glucose levels after meals in youth with CF. Our findings for gut hormone release will inform investigation of potential therapies, eg. free fatty acid therapy, to prime gut hormone release to reduce the impact of high blood glucose levels on the complications associated with CF.

Hypothesis : In young people with CF
i) Gut emptying of a high fat/carbohydrate meal will be abnormally rapid.
ii) Abnormal emptying will be associated with high blood glucose levels after a meal and reduced gut hormone secretion and insulin responses.
iii) These abnormal responses will be normalised by pancreatic enzyme supplementation.
Trial website
None
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34263 0
Dr Shiree Perano
Address 34263 0
72 King William Road
North Adelaide 5006
SA
Country 34263 0
Australia
Phone 34263 0
+61 8 81617000
Fax 34263 0
Email 34263 0
[email protected]
Contact person for public queries
Name 17510 0
Dr Dr Shiree Perano
Address 17510 0
72 King William Road
North Adelaide 5006
SA
Country 17510 0
Australia
Phone 17510 0
+61 8 8161 7000
Fax 17510 0
Email 17510 0
[email protected]
Contact person for scientific queries
Name 8438 0
Dr Dr Shiree Perano
Address 8438 0
72 King William Road
North Adelaide 5006
SA
Country 8438 0
Australia
Phone 8438 0
+61 8 8161 7000
Fax 8438 0
Email 8438 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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