Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001239550
Ethics application status
Approved
Date submitted
9/11/2015
Date registered
12/11/2015
Date last updated
25/11/2019
Date data sharing statement initially provided
25/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Bile acids and glycemic control in type 2 diabetes
Scientific title
Effects of intrajejunal taurocholic acid on glycaemia, gastrointestinal hormone secretion and small intestinal glucose absorption in response to intrajejunal glucose infusion in type 2 diabetes.
Secondary ID [1] 287828 0
None
Universal Trial Number (UTN)
None
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes mellitus 296716 0
Condition category
Condition code
Metabolic and Endocrine 296950 296950 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, in a double-blind, randomised fashion:
(1) intrajejunal infusion of saline (+ i.v. saline)
(2) intrajejunal infusion of taurocholic acid (TCA) (+ i.v. saline)
(3) intrajejunal infusion of saline (+ i.v. exendin (9-39))
(4) intrajejunal infusion of TCA (+ i.v. exendin (9-39))
An intravenous infusion of exendin (9-39) (Bachem, Clinalfa products, L?ufelfingen, Switzerland) at 600 pmol/kg/min (a rate known to be well tolerated and to block >95% of the actions of endogenous GLP-1 in humans), or 0.9% saline, will be commenced at T = -60 min, and maintained until T = 120 min. Intrajejunal infusion of either TCA (4g TCA dissolved in 240 mL 0.9% saline), or 0.9% saline, will be commenced at the rate of 240 mL/hour during T -30-0 min, and reduced to the rate of 60 mL/hour during T = 0-120 min. At T = 0 min, subjects will also receive a small intestinal infusion consisting of 60 g glucose with 5 g 3-O-methylglucose (3-OMG) dissolved in water to a total volume of 240 mL, infused over 120 minutes (2 mL/min, and 2 kcal/min).
Intervention code [1] 293217 0
Treatment: Drugs
Comparator / control treatment
Intravenous and intrajejunal infusions of 0.9% saline
Control group
Placebo

Outcomes
Primary outcome [1] 296559 0
the difference in iAUC for blood glucose between treatments
Timepoint [1] 296559 0
T = -60, -30, 0, 15, 30, 60, 75, 90, 105 and 120 min, where T = -60 min is at start of either iv. exendin(9-39) or 0.9% saline, T = -30 min at start of intrajejunal TCA or saline infusion, and T = 0 min at start of intrajejunal glucose infusion.
Secondary outcome [1] 318752 0
differences in serum 3-OMG
Timepoint [1] 318752 0
at T = -60, -30, 0, 15, 30, 60, 75, 90, 105, 120 for measurement of 3-OMG, where T = -60 min is at start of either iv. exendin(9-39) or 0.9% saline, T = -30 min at start of intrajejunal TCA or saline infusion, and T = 0 min at start of intrajejunal glucose infusion.
Secondary outcome [2] 318773 0
differences in plasma GLP-1
Timepoint [2] 318773 0
at T = -60, -30, 0, 15, 30, 60, 75, 90, 105, 120 for measurement of plasma GLP-1, where T = -60 min is at start of either iv. exendin(9-39) or 0.9% saline, T = -30 min at start of intrajejunal TCA or saline infusion, and T = 0 min at start of intrajejunal glucose infusion.
Secondary outcome [3] 318774 0
differences in plasma GIP
Timepoint [3] 318774 0
at T = -60, -30, 0, 15, 30, 60, 75, 90, 105, 120 for measurement of plasma GIP, where T = -60 min is at start of either iv. exendin(9-39) or 0.9% saline, T = -30 min at start of intrajejunal TCA or saline infusion, and T = 0 min at start of intrajejunal glucose infusion.
Secondary outcome [4] 318775 0
differences in plasma insulin
Timepoint [4] 318775 0
at T = -60, -30, 0, 15, 30, 60, 75, 90, 105, 120 for measurement of plasma insulin, where T = -60 min is at start of either iv. exendin(9-39) or 0.9% saline, T = -30 min at start of intrajejunal TCA or saline infusion, and T = 0 min at start of intrajejunal glucose infusion.
Secondary outcome [5] 318776 0
differences in plasma C-peptide
Timepoint [5] 318776 0
at T = -60, -30, 0, 15, 30, 60, 75, 90, 105, 120 for measurement of plasma C-peptide, where T = -60 min is at start of either iv. exendin(9-39) or 0.9% saline, T = -30 min at start of intrajejunal TCA or saline infusion, and T = 0 min at start of intrajejunal glucose infusion.
Secondary outcome [6] 318777 0
differences in plasma glucagon
Timepoint [6] 318777 0
at T = -60, -30, 0, 15, 30, 60, 75, 90, 105, 120 for measurement of plasma glucagon, where T = -60 min is at start of either iv. exendin(9-39) or 0.9% saline, T = -30 min at start of intrajejunal TCA or saline infusion, and T = 0 min at start of intrajejunal glucose infusion.
Secondary outcome [7] 318778 0
differences in plasma FGF-19
Timepoint [7] 318778 0
at T = -60, -30, 0, 15, 30, 60, 75, 90, 105, 120 for measurement of plasma FGF-19, where T = -60 min is at start of either iv. exendin(9-39) or 0.9% saline, T = -30 min at start of intrajejunal TCA or saline infusion, and T = 0 min at start of intrajejunal glucose infusion.
Secondary outcome [8] 318779 0
differences in BP, measured by an automated sphygmomanometer.
Timepoint [8] 318779 0
every 5min from T = -60 to 120 min, where T = -60 min is at start of either iv. exendin(9-39) or 0.9% saline, T = -30 min at start of intrajejunal TCA or saline infusion, and T = 0 min at start of intrajejunal glucose infusion.
Secondary outcome [9] 318780 0
differences in HR, measured simultaneously with BP by an automated sphygmomanometer.
Timepoint [9] 318780 0
every 5min from T = -60 to 120 min, where T = -60 min is at start of either iv. exendin(9-39) or 0.9% saline, T = -30 min at start of intrajejunal TCA or saline infusion, and T = 0 min at start of intrajejunal glucose infusion.

Eligibility
Key inclusion criteria
* Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet or metformin only
* Body mass index (BMI) 20 - 40 kg/m2
* Age 18 - 75 years
* Males and post-menopausal females
* Glycated haemoglobin (HbA1c) less than or equal to 8.5%
* Haemoglobin above the lower limit of the normal range (ie. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. >30ng/mL for men and >20mg/mL for women)
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Use of any medication that may influence gastrointestinal motor function within 48 hours or 5 half lives of the study, specifically: opiates, anticholinergics, levodopa, beta blockers, clonidine, nitrates, tricyclic antidepressants, selective serotonin re-uptake inhibitors, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, tegaserod, or erythromycin
* Evidence of drug abuse, or 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
* Participants who do not eat beef
* Vegetarian diet

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)
Independently randomised and blinded by hospital pharmacy
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
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
14 subjects will provide 80% power (at a = 0.008 in order to allow for corrections for multiple subgroup comparisons) to detect a difference of 93 mmol/L × min in the incremental under the curve (iAUC) for blood glucose with a SD of 94 mmol/L × min between the treatments.
Data will be analysed using standardised, non-parametric or parametric statistical methods where appropriate (e.g. repeated measures ANOVA).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/11/2015
Actual
3/03/2016
Date of last participant enrolment
Anticipated
9/12/2016
Actual
7/06/2017
Date of last data collection
Anticipated
Actual
24/07/2017
Sample size
Target
14
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 4589 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 12194 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 292350 0
Government body
Name [1] 292350 0
NHMRC
Country [1] 292350 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace, Adelaide
SA 5000
Country
Australia
Secondary sponsor category [1] 291029 0
None
Name [1] 291029 0
Address [1] 291029 0
Country [1] 291029 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293814 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 293814 0
Ethics committee country [1] 293814 0
Australia
Date submitted for ethics approval [1] 293814 0
28/07/2015
Approval date [1] 293814 0
05/08/2015
Ethics approval number [1] 293814 0
150715

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

Contacts
Principal investigator
Name 61422 0
Prof Chris Rayner
Address 61422 0
Discipline of Medicine,
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace
Adelaide, SA 5000
Country 61422 0
Australia
Phone 61422 0
+61 8 8222 2916
Fax 61422 0
+61 8 8223 3870
Email 61422 0
[email protected]
Contact person for public queries
Name 61423 0
Tongzhi Wu
Address 61423 0
Discipline of Medicine,
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace
Adelaide, SA 5000
Country 61423 0
Australia
Phone 61423 0
+61 8 8222 5038
Fax 61423 0
+61 8 8223 3870
Email 61423 0
[email protected]
Contact person for scientific queries
Name 61424 0
Tongzhi Wu
Address 61424 0
Discipline of Medicine,
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace
Adelaide, SA 5000
Country 61424 0
Australia
Phone 61424 0
+61 8 8222 5038
Fax 61424 0
+61 8 8223 3870
Email 61424 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.