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Trial registered on ANZCTR


Registration number
ACTRN12615001240538
Ethics application status
Approved
Date submitted
9/11/2015
Date registered
12/11/2015
Date last updated
18/10/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Regional glucose infusion on gut function
Scientific title
Comparative effects of intraduodenal (ID) vs. intraileal (II) glucose on incretin hormone secretion, incretin effect, and glycaemic excursions in healthy subjects and patients with type 2 diabetes.
Secondary ID [1] 287830 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glucose metabolism 296719 0
Condition category
Condition code
Metabolic and Endocrine 296952 296952 0 0
Normal metabolism and endocrine development and function
Metabolic and Endocrine 296973 296973 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following an overnight fast, each subject will receive the following four treatments, separated by at least 7 days:
(1) intraduodenal (ID) glucose infusion at a rate of 2 kcal/min
(2) IV glucose infusion at a variable rate designed to match the blood glucose profile of the ID study day (ie. an isoglycaemic infusion)
(3) intraileal (II) glucose infusion at a rate of 2 kcal/min
(4) IV isoglycaemic infusion to match the blood glucose profile of the II study day
The order of ID and II infusion is randomised, while each IV isoglycaemic infusion is administered following ID or ID infusion.
ID or II infusion days:
For ID infusion, the catheter will be positioned with the infusion port located 10 cm distal to the pylorus. For II infusion, the infusion port will be positioned 200 cm distal to the pylorus. Once the intraluminal catheter is correctly positioned, 30 g glucose (together with 3 g 3-O-methylglucose (3-OMG) for assessment of glucose absorption), dissolved in water to a total volume of 120 mL, will be infused into the duodenum or mid-ileum for 60 min (t = 0 – 60 min, ie. 2 kcal/min). At the end of infusion (t = 60 min), the catheter will be removed. “Arterialised” blood samples (10 mL) will be sampled at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min. At t = 180 min, each subject will be given a meal and monitored to ensure stable blood glucose concentrations over the next 60 min, after which they will be allowed to leave the laboratory.
IV “isoglycaemic” infusion days:
An IV cannula will be placed in a forearm vein for IV administration of 25% glucose to mimic the glycaemic excursions on the preceding ID or II glucose infusion study visit. The infusion will be guided by recording blood glucose every 5 minutes and adjusting infusion rate accordingly (Medisense Precision QID, Abbott Laboratories, Bedford, MA, USA). “Arterialised” blood samples (10 mL) will be also be sampled at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min for subsequent measurement of plasma concentrations of GLP-1, GIP, insulin, C-peptide and glucagon. At t = 180 min, each subject will be given a meal and monitored to ensure stable blood glucose concentrations over the next 60 min, after which they will be allowed to leave the laboratory.

Intervention code [1] 293218 0
Treatment: Other
Comparator / control treatment
intraduodenal glucose infusion and the matching IV glucose infusion (i.e. arms 1 and 2)
Control group
Active

Outcomes
Primary outcome [1] 296560 0
differences in the iAUC for blood glucose after ID vs. II glucose infusion at 2 kcal/min
Timepoint [1] 296560 0
at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t=0 min is start of glucose administration.
Primary outcome [2] 296575 0
differences in the iAUC for plasma GLP-1 after ID vs. II glucose infusion at 2 kcal/min
Timepoint [2] 296575 0
at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t=0 min is start of glucose administration.
Primary outcome [3] 296576 0
differences in the iAUC for plasma GIP after ID vs. II glucose infusion at 2 kcal/min
Timepoint [3] 296576 0
at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t=0 min is start of glucose administration.
Secondary outcome [1] 318785 0
differences in the iAUC for plasma insulin after ID vs. II glucose infusion at 2 kcal/min
Timepoint [1] 318785 0
at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t=0 min is start of glucose administration.
Secondary outcome [2] 318786 0
differences in the iAUC for plasma C-peptide after ID vs. II glucose infusion at 2 kcal/min
Timepoint [2] 318786 0
at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t=0 min is start of glucose administration.
Secondary outcome [3] 318787 0
differences in the iAUC for plasma glucagon after ID vs. II glucose infusion at 2 kcal/min
Timepoint [3] 318787 0
at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t=0 min is start of glucose administration.
Secondary outcome [4] 318788 0
difference in BP during ID vs II glucose infusion. BP is assessed using an automated sphygmomanometer.
Timepoint [4] 318788 0
every 5 min from t = 0 to 180 min, where t=0 is start of glucose administration.
Secondary outcome [5] 318789 0
difference in HR during ID vs II glucose infusion. HR is assessed simultaneously with BP using an automated sphygmomanometer.
Timepoint [5] 318789 0
every 5 min from t = 0 to 180 min, where t=0 is start of glucose administration.
Secondary outcome [6] 318790 0
difference in SMA during ID vs II glucose infusion. SMA is assessed by ultrasound.
Timepoint [6] 318790 0
at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t=0 min is start of glucose administration.

Eligibility
Key inclusion criteria
Type 2 diabetic subjects
*Managed by diet alone (i.e. no oral hypoglycaemic drugs or insulin)
*Body mass index (BMI) 20 - 35 kg/m2
*Age 18 - 75 years
*Males and post-menopausal females (to control for the effect of the menstrual cycle on gut hormone secretion)
*Glycated haemoglobin (HbA1c) greater than or equal to 6.0% and less than or equal to 7.9%
*Haemoglobin above the lower limit of the normal range (i.e. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (i.e. >10mcg/L)

Healthy subjects
*Male and postmenopausal females aged 18 – 75 years
*Body mass index (BMI) 20 - 35 kg/m2
*Age- and BMI-matched to the diabetic subjects
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
*Use of any medication that may influence BP, gastrointestinal motor function, body weight or appetite (e.g. antihypertensive drugs, domperidone and cisapride, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St. John's Wort etc.)
*Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes on a daily basis
*History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy)
*Other significant illness, including epilepsy, cardiovascular or respiratory disease
*Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests (> 2 times upper limit of normal range))
*Donation of blood within the previous 3 months
*Participation in any other research studies within the previous 3 months
*Females who are pre-menopausal
*Inability to give informed consent
*Vegetarians

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on our unpublished comparative data from ID and IJ glucose infusion studies at a rate of 2 kcal/min in healthy subjects, we anticipate that 16 subjects in each group will provide 80% power (at a = 0.05) to detect a difference of 70 mmol/L × min in the area under the curve (AUC) for blood glucose, with a standard deviation (SD) of 90 mmol/L × min between ID and II glucose infusion at 2 kcal/min. This sample size will also give 97% power (at a = 0.05) to detect a difference of 1074 pmol/L × min in the AUC for plasma GLP-1, with an SD of 1043 pmol/L × min, and 87% power (at a = 0.05) to detect a difference of 1724 mU/L × min in the AUC for plasma insulin, with an SD of 2100 mU/L × min.
Data will be analysed using standardised, non-parametric or parametric statistical methods where appropriate (e.g. repeated measures ANOVA). The data will be prepared for publication in a peer-reviewed journal.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
12/01/2015
Date of last participant enrolment
Anticipated
29/02/2016
Actual
14/01/2016
Date of last data collection
Anticipated
Actual
14/01/2016
Sample size
Target
32
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 4590 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 12195 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 292352 0
Government body
Name [1] 292352 0
NHMRC
Country [1] 292352 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 291031 0
None
Name [1] 291031 0
Address [1] 291031 0
Country [1] 291031 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293816 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 293816 0
Ethics committee country [1] 293816 0
Australia
Date submitted for ethics approval [1] 293816 0
01/08/2014
Approval date [1] 293816 0
02/09/2014
Ethics approval number [1] 293816 0
140816

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61430 0
Prof Chris Rayner
Address 61430 0
Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA, 5000.
Country 61430 0
Australia
Phone 61430 0
+61 8 8222 2916
Fax 61430 0
Email 61430 0
chris.rayner@adelaide.edu.au
Contact person for public queries
Name 61431 0
Tongzhi Wu
Address 61431 0
Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA, 5000.
Country 61431 0
Australia
Phone 61431 0
+61 8 8222 5038
Fax 61431 0
Email 61431 0
tongzhi.wu@adelaide.edu.au
Contact person for scientific queries
Name 61432 0
Tongzhi Wu
Address 61432 0
Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA, 5000.
Country 61432 0
Australia
Phone 61432 0
+61 8 8222 5038
Fax 61432 0
Email 61432 0
tongzhi.wu@adelaide.edu.au

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffects of proximal and distal enteral glucose infusion on cardiovascular response in health and type 2 diabetes.2021https://dx.doi.org/10.1210/CLINEM/DGAA341
N.B. These documents automatically identified may not have been verified by the study sponsor.