Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000243314
Ethics application status
Approved
Date submitted
16/02/2017
Date registered
17/02/2017
Date last updated
4/06/2019
Date data sharing statement initially provided
21/01/2019
Date results provided
4/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Gastrointestinal mechanisms underlying glucose lowering by metformin in type 2 diabetes
Scientific title
The glycaemic and hormonal effects of metformin when administered to the distal vs proximal small intestine in type 2 diabetes
Secondary ID [1] 291173 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes mellitus 302051 0
Condition category
Condition code
Metabolic and Endocrine 301684 301684 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following a screening visit, each subject will be studied on 3 occasions, separated by at least 7 days, in a double-blinded randomised order. On each study day, a customised multilumen silicone catheter will be inserted nasally into the gastrointestinal (GI) tract. Passage to the desired small intestinal depth will be confirmed by continuous measurement of the transmucosal potential difference between proximal and distal channels along with the use of a reference electrode inserted subcutaneously into the left forearm. Once correctly positioned, one of three treatments will be administered: 0.9% saline (control), ‘proximal metformin’ 1000 mg (10cm beyond pylorus), or ‘distal metformin’ 1000 mg (190cm beyond pylorus) over 5 min, followed 60 min later by an oral glucose drink (containing 50 g glucose). The catheter will be removed 10 minutes prior to an oral glucose load.
Intervention code [1] 297173 0
Treatment: Drugs
Comparator / control treatment
50mL 0.9% saline infusions into the proximal and distal small intestine during one of the 3 study visits.
Control group
Placebo

Outcomes
Primary outcome [1] 301090 0
differences in the incremental area under the curve (iAUC) for plasma glucose between the 3 treatments.
Timepoint [1] 301090 0
at t = -60, -45, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150 and 180 min where t = -60 is when the intraluminal catheter is correctly positioned and t = 0 is when oral glucose given.
Primary outcome [2] 301091 0
differences in the incremental area under the curve (iAUC) for plasma GLP-1 between the 3 treatments.
Timepoint [2] 301091 0
at t = -60, -30, 0, 15, 30, 45, 60, 90, 120, 150 and 180 min where t = -60 is when the intraluminal catheter is correctly positioned and t = 0 is when oral glucose given.
Primary outcome [3] 301092 0
differences in the gastric half-emptying time (T50) derived from 13CO2 concentrations in the breath samples between the 3 treatments.
Timepoint [3] 301092 0
breath samples collected immediately before (t=0) and every 5 min after oral glucose in the first hour and every 15 min for a further 2 hours. t = 0 is when oral glucose is given.
Secondary outcome [1] 331702 0
differences in the incremental area under the curve (iAUC) for plasma insulin
Timepoint [1] 331702 0
at t = -60, -30, 0, 15, 30, 45, 60, 90, 120, 150 and 180 min where t = -60 is when the intraluminal catheter is correctly positioned and t = 0 is when oral glucose given.
Secondary outcome [2] 331703 0
differences in the incremental area under the curve (iAUC) for plasma glucagon between the 3 treatments
Timepoint [2] 331703 0
at t = -60, -30, 0, 15, 30, 45, 60, 90, 120, 150 and 180 min where t = -60 is when the intraluminal catheter is correctly positioned and t = 0 is when oral glucose given.
Secondary outcome [3] 331704 0
differences in the incremental area under the curve (iAUC) for plasma 3OMG between the 3 treatments.
Timepoint [3] 331704 0
at t = -60, -30, 0, 15, 30, 45, 60, 90, 120, 150 and 180 min where t = -60 is when the intraluminal catheter is correctly positioned and t = 0 is when oral glucose given.
Secondary outcome [4] 331705 0
differences in the incremental area under the curve (iAUC) for plasma lactate between the 3 treatments.
Timepoint [4] 331705 0
at t = -60, -30, 0, 15, 30, 45, 60, 90, 120, 150 and 180 min where t = -60 is when the intraluminal catheter is correctly positioned and t = 0 is when oral glucose given.
Secondary outcome [5] 331706 0
differences in the incremental area under the curve (iAUC) for plasma metformin between the 3 treatments.
Timepoint [5] 331706 0
at t = -60, -30, 0, 15, 30, 45, 60, 90, 120, 150 and 180 min where t = -60 is when the intraluminal catheter is correctly positioned and t = 0 is when oral glucose given.
Secondary outcome [6] 331707 0
differences in the incremental area under the curve (iAUC) for blood pressure between the 3 treatments
Timepoint [6] 331707 0
every 5 minutes during the study period from t = -60 to 180 min where t = -60 is when the intraluminal catheter is correctly positioned and t = 0 is when oral glucose given.
Secondary outcome [7] 331708 0
differences in the incremental area under the curve (iAUC) for heart rate between the 3 treatments.
Timepoint [7] 331708 0
every 5 minutes during the study period from t = -60 to 180 min where t = -60 is when the intraluminal catheter is correctly positioned and t = 0 is when oral glucose given.

Eligibility
Key inclusion criteria
Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet only
Body mass index (BMI) 20 - 40 kg/m2
Males and post-menopausal females
Glycated haemoglobin (HbA1c) less than 8.5%
Haemoglobin above the lower limit of the normal range (ie. greater than 135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. greater than 30ng/mL for men and greater than 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, clonidine, nitrates, 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 less than 90 mL/min or abnormal liver function tests (greater 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
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)
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 receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/02/2017
Actual
3/04/2017
Date of last participant enrolment
Anticipated
1/06/2017
Actual
14/08/2018
Date of last data collection
Anticipated
30/06/2017
Actual
10/10/2018
Sample size
Target
12
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 7491 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 15316 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 295615 0
Government body
Name [1] 295615 0
Diabetes Australia
Country [1] 295615 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
Level 6, Eleanor Harrald Building
Frome Road
Royal Adelaide Hospital
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 294451 0
None
Name [1] 294451 0
Address [1] 294451 0
Country [1] 294451 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296933 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 296933 0
Ethics committee country [1] 296933 0
Australia
Date submitted for ethics approval [1] 296933 0
24/11/2016
Approval date [1] 296933 0
23/12/2016
Ethics approval number [1] 296933 0
R20161132

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

Contacts
Principal investigator
Name 72478 0
Dr Dr Tongzhi Wu
Address 72478 0
Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA 5000
Country 72478 0
Australia
Phone 72478 0
+61 8 8222 5038
Fax 72478 0
Email 72478 0
[email protected]
Contact person for public queries
Name 72479 0
Tongzhi Wu
Address 72479 0
Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA 5000
Country 72479 0
Australia
Phone 72479 0
+61 8 8222 5038
Fax 72479 0
Email 72479 0
[email protected]
Contact person for scientific queries
Name 72480 0
Tongzhi Wu
Address 72480 0
Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA 5000
Country 72480 0
Australia
Phone 72480 0
+61 8 8222 5038
Fax 72480 0
Email 72480 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


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
EmbaseMetformin attenuates the postprandial fall in blood pressure in type 2 diabetes.2019https://dx.doi.org/10.1111/dom.13632
N.B. These documents automatically identified may not have been verified by the study sponsor.