Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001086156
Ethics application status
Approved
Date submitted
29/07/2019
Date registered
6/08/2019
Date last updated
3/12/2020
Date data sharing statement initially provided
6/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of endogenous bile acids on postprandial glucose levels in health and type 2 diabetes
Scientific title
Effects of endogenous bile acids on postprandial glucose metabolism in health and type 2 diabetes, and the impact of small intestinal region exposed.
Secondary ID [1] 298871 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 313830 0
Obesity 313831 0
Condition category
Condition code
Metabolic and Endocrine 312232 312232 0 0
Diabetes
Diet and Nutrition 312233 312233 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following enrolment, each subject will be studied on 3 occasions, separated by at least 7 days, in a single-blind, randomized fashion.

On each study day, a silicone rubber catheter will be inserted by an experienced research officer through an anaesthetised nostril into the stomach, and allowed to pass into the small intestine by peristalsis. The catheter will be positioned with the two infusion ports (i.e. proximal and distal small intestinal infusion ports) located at 50 cm (i.e. the jejunum) and 190 cm (i.e. the ileum) beyond the pylorus, respectively, while subjects laid in a supine position. An inflatable self-contained balloon (5 cm in length, with a maximum volume of 100 mL) situated 30 cm below the pylorus, that can be inflated as a barrier between the duodenum and the jejunum, and an aspiration channel 25 cm distal to the pylorus (to aspirate endogenous bile). The correct positioning of the catheter will be monitored continuously by measurement of the transmucosal potential difference in the stomach (~ -40 mV) and the duodenum (~ 0 mV). For this purpose, an intravenous cannula will be placed subcutaneously in the left forearm by our experienced research office rand filled with sterile saline as a reference electrode. An intravenous cannula will be placed into a vein on the dorsum of the hand, which will be kept warm with a heat pad to allow sampling of “arterialised” blood.

Once the intraluminal catheter is correctly positioned, the balloon will be slowly inflated with air (~30-40 mL) until the subject reports a sensation of pressure without discomfort. An intra-balloon pressure of at least 20 mmHg (a known pressure to be sufficient to achieve full blockade) will be maintained by continuous monitoring with a pressure gauge throughout the study (t = 0 - 180 min). The aspiration channel will be connected to negative pressure drainage to allow constant aspiration of secretions from the duodenum.

At t = 0 min, subjects will receive intrajejunal glucose infusion at 3 kcal/min (67.5 g glucose dissolved in water to a total volume of 180 mL, infused over 90 minutes). Meanwhile, endogenous bile will be aspirated consciously and one of the following three interventions will be conducted by one of the investigators:
(i) stored separately for analysis
(ii) re-perfused into the proximal jejunum (every 5 minutes, for 180 minutes)
(iii) re-perfused into the ileum (every 5 minutes, for 180 minutes).
The volume of bile re-perfused is whatever was aspirated in the previous 5 minutes. Sites without reperfusion of endogenous bile will be perfused with 0.9% saline to control for the volume infused. At t = 180 min, the catheter will be removed.
Intervention code [1] 315135 0
Treatment: Other
Comparator / control treatment
1. Aspirate bile and stored separately for analysis,
2. Aspirate bile and re-perfuse into the proximal jejunum (control treatment) (this is very close to physiological condition in which bile released into the duodenum after meal),
3. Aspirate bile and re-perfuse into the ileum.
Control group
Active

Outcomes
Primary outcome [1] 320879 0
the difference in the iAUC for plasma glucose between the treatments
Timepoint [1] 320879 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t = 0 is when intrajejunal glucose infusion starts.
Secondary outcome [1] 373213 0
the differences in the iAUCs for plasma total GLP-1 between the treatments
Timepoint [1] 373213 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t = 0 is when intrajejunal glucose infusion starts.
Secondary outcome [2] 373214 0
the differences in the iAUCs for plasma insulin between the treatments
Timepoint [2] 373214 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t = 0 is when intrajejunal glucose infusion starts.
Secondary outcome [3] 373215 0
the differences in the iAUCs for plasma C-peptide between treatments
Timepoint [3] 373215 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t = 0 is when intrajejunal glucose infusion starts.
Secondary outcome [4] 373216 0
the differences in the iAUCs for plasma glucagon between treatments
Timepoint [4] 373216 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t = 0 is when intrajejunal glucose infusion starts.
Secondary outcome [5] 373217 0
the differences in the iAUCs for plasma FGF19 between treatments
Timepoint [5] 373217 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 min, where t = 0 is when intrajejunal glucose infusion starts.

Eligibility
Key inclusion criteria
(i) Patients with type 2 diabetes (World Health Organisation (WHO) criteria), HbA1c less than or equal to 8.5%, managed by diet or metformin alone, body mass index from 20 to 35 kg/m2, both males and females aged from 18 to 75 years
(ii) Healthy volunteers, matched as closely as possible to the diabetic subjects for age, sex, and BMI.
Additional inclusion criteria include: haemoglobin above the lower limit of the normal range (ie. more than 135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. more than 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?
Yes
Key exclusion criteria
Exclusion criteria
• Use of any medication that may influence gastrointestinal motor function, bile acid metabolism, body weight or appetite (e.g. bile acid sequestrants, 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 less than 90 mL/min or abnormal liver function tests (more than 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
• Inability to give informed consent
• Female participants who are pregnant or planning for pregnancy, or are lactating
• 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)
Ssealed 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 (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving 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 data derived from our previous studies, 16 subjects will provide at least 80% power to detect a 30% difference in the incremental area under the curve (iAUC) over 180 min for plasma glucose between treatments, in response to a standardized intrajejunal glucose infusion (3 kcal/min over 90 min). Significance is set at a = 0.016 to enable corrections of post hoc comparisons. We will require 20 subjects for both health and patients with type 2 diabetes group to allow for drop-outs.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
19/08/2019
Actual
8/10/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
6
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 14341 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 27344 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 303416 0
Self funded/Unfunded
Name [1] 303416 0
Not funded yet
Country [1] 303416 0
Primary sponsor type
University
Name
University of Adelaide
Address
Clinical Research Facility, Level 4 Adelaide Health and Medical Sciences (AHMS) Building,
North Terrace
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 303465 0
None
Name [1] 303465 0
None
Address [1] 303465 0
None
Country [1] 303465 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303946 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 303946 0
Ethics committee country [1] 303946 0
Australia
Date submitted for ethics approval [1] 303946 0
08/06/2019
Approval date [1] 303946 0
23/07/2019
Ethics approval number [1] 303946 0
HREC/19/CALHN/337

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

Contacts
Principal investigator
Name 95338 0
Dr Tongzhi Wu
Address 95338 0
Adelaide Medical School, the University of Adelaide
Level 5 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace,
Adelaide, SA 5000
Country 95338 0
Australia
Phone 95338 0
+61 8 8313 6535
Fax 95338 0
Email 95338 0
[email protected]
Contact person for public queries
Name 95339 0
Tongzhi Wu
Address 95339 0
Adelaide Medical School, the University of Adelaide
Level 5 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace,
Adelaide, SA 5000
Country 95339 0
Australia
Phone 95339 0
+61 8 8313 6535
Fax 95339 0
Email 95339 0
[email protected]
Contact person for scientific queries
Name 95340 0
Tongzhi Wu
Address 95340 0
Adelaide Medical School, the University of Adelaide
Level 5 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace,
Adelaide, SA 5000
Country 95340 0
Australia
Phone 95340 0
+61 8 8313 6535
Fax 95340 0
Email 95340 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The ethical statement and informed consent do not allow for free data 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
No additional documents have been identified.