Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000305123
Ethics application status
Approved
Date submitted
25/02/2019
Date registered
27/02/2019
Date last updated
21/06/2022
Date data sharing statement initially provided
27/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Can loss of response to the gut hormone, glucose-dependent insulinotropic polypeptide (GIP), be reversed in type 2 diabetes?
Scientific title
Can loss of response to the gut hormone, glucose-dependent insulinotropic polypeptide (GIP), be reversed in type 2 diabetes?
Secondary ID [1] 297504 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes mellitus 311694 0
Condition category
Condition code
Metabolic and Endocrine 310320 310320 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following enrolment (within 1-2 weeks), each subject will commence 12 weeks treatment with capsules containing sitagliptin (100 mg daily) in an open label design, supplied via the Royal Adelaide Hospital Pharmacy. During each of weeks 1 and 12, they will attend the laboratory twice for intraduodenal infusion studies, 2-5 days apart. On the evening preceding the study day (~1900h), participants will be given a standardised evening meal (~591 kcal, 55% carbohydrate, 14% protein and 31% fat). Following this meal, participants will be asked to fast from solids and liquids (other than water) until the following morning, when they will attend the CRF of the AHMS building at 0800h.
On each study day, a silicone rubber catheter will be inserted through an anaesthetised nostril into the stomach, and be positioned with the infusion port located 12 cm below to the pylorus (in the duodenum). An intravenous cannula will be placed into a vein of each forearm for hyperglycaemic clamping and infusion of the GIP antagonist GIP(3-30)NH2 (or saline control) and blood sampling, respectively.
After correct positioning of the intraduodenal catheter, a hyperglycaemic clamp will be maintained at 15 mmol/L from t = 0 to 270 min. This is achieved by intravenous administration of an initial bolus of 25% dextrose, followed by a 25% dextrose infusion at a rate adjusted according to blood glucose concentrations measured every 5 min. Concurrently, a solution of 100 units of insulin, made up to 500 ml with Gelofusine to yield a final concentration of 0.2 IU/ml, will also be infused intravenously at rates according to a sliding scale used in previous similar studies. An IV infusion of the GIP antagonist GIP(3-30)NH2 at the rate of 800 pmol/kg/min, or saline control, will run from t = 30 to 270 min. Intraduodenal glucose will be infused at 2 kcal/min from t = 90 to 190 min.
During the 12 week intervention, subjects will keep a daily diary for study medication, receive a fortnightly telephone call to reinforce compliance and document any adverse effects, and visit our centre in weeks 4 and 8 to return any unused medication, receive the next 4 weeks’ supply and undergo repeated physical examinations and assessment of liver and renal function.
Intervention code [1] 313746 0
Treatment: Drugs
Comparator / control treatment
IV infusion of 0.9% saline
Control group
Placebo

Outcomes
Primary outcome [1] 319205 0
The difference in the insulinotropic response to intraduodenal glucose between intravenous GIP antagonist and saline control (evaluated as the increment in area under the curve (AUC) for C-peptide from t = 70-210 min at weeks 1 and 12).
Timepoint [1] 319205 0
at t = 90, 95, 100, 105, 110, 115, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260 and 270min where t= 0 is when intraluminal catheter is correctly positioned and a hyperglycaemic clamp starts and t = 90 is when intraduodenal glucose infusion starts.
Secondary outcome [1] 367274 0
The difference in plasma concentrations of insulin between intravenous GIP antagonist and saline control at weeks 1 and 12.
Timepoint [1] 367274 0
at t = 0, 30, 60, 90, 120, 150, 180, 210, 240 and 270min. where t= 0 is when intraluminal catheter is correctly positioned and a hyperglycaemic clamp starts and t = 90 is when intraduodenal glucose infusion starts.
Secondary outcome [2] 367275 0
Differences in glucagon between intravenous GIP antagonist and saline control at weeks 1 and 12.
Timepoint [2] 367275 0
at t = 0, 30, 60, 90, 120, 150, 180, 210, 240 and 270min. where t= 0 is when intraluminal catheter is correctly positioned and a hyperglycaemic clamp starts and t = 90 is when intraduodenal glucose infusion starts.
Secondary outcome [3] 367277 0
Differences in total GIP between intravenous GIP antagonist and saline control at weeks 1 and 12.
Timepoint [3] 367277 0
at t = 0, 30, 60, 90, 120, 150, 180, 210, 240 and 270min. where t= 0 is when intraluminal catheter is correctly positioned and a hyperglycaemic clamp starts and t = 90 is when intraduodenal glucose infusion starts.
Secondary outcome [4] 367297 0
Differences in total GLP-1 between intravenous GIP antagonist and saline control at weeks 1 and 12.
Timepoint [4] 367297 0
at t = 0, 30, 60, 90, 120, 150, 180, 210, 240 and 270min. where t= 0 is when intraluminal catheter is correctly positioned and a hyperglycaemic clamp starts and t = 90 is when intraduodenal glucose infusion starts.
Secondary outcome [5] 367298 0
Differences in IV glucose infused by measuring the quantity of used glucose between intravenous GIP antagonist and saline control.
Timepoint [5] 367298 0
at week 1 and 12.

Eligibility
Key inclusion criteria
• Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet and/or metformin (stable dose for equal to 3 months) only
• Body mass index (BMI) from 20 to 35 kg/m2
• Males and females, aged from 40 to 79 years
• Glycated haemoglobin (HbA1c) from 7.1 to 8.0%
• 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
40 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Use of any medication that may influence gastrointestinal motor function, body weight or appetite (opiates, anticholinergics, levodopa, clonidine, nitrates, tricyclic antidepressants, selective serotonin re-uptake inhibitors, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, prucalopride, or erythromycin)
• 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
• 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)
allocation involved contacting the holder of the allocation schedule who was "off-site" or at central administration site (Royal Adelaide 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 receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on previous data, 15 subjects will provide at least 80% power to detect a 20% difference in insulin secretion with the GIP antagonist. We will recruit 18 subjects to allow for a modest dropout rate.
Data will be analysed using standardised, non-parametric or parametric statistical methods where appropriate (e.g. repeated measures ANOVA).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/04/2019
Actual
5/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 13238 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 25796 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 302063 0
Government body
Name [1] 302063 0
NHMRC
Country [1] 302063 0
Australia
Primary sponsor type
University
Name
University
Address
Adelaide Medical School, Level 5 Adelaide Health and Medical Sciences (AHMS) Building,
North Terrace, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 301874 0
None
Name [1] 301874 0
Address [1] 301874 0
Country [1] 301874 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302744 0
CALHN Human Research Ethics Committee
Ethics committee address [1] 302744 0
Ethics committee country [1] 302744 0
Australia
Date submitted for ethics approval [1] 302744 0
03/11/2018
Approval date [1] 302744 0
20/02/2019
Ethics approval number [1] 302744 0
HREC/18/CALHN/737

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

Contacts
Principal investigator
Name 91246 0
Prof Chris Rayner
Address 91246 0
Adelaide Medical School, the University of Adelaide, Level 5 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace, Adelaide, SA 5000
Country 91246 0
Australia
Phone 91246 0
+61 8 8313 6693
Fax 91246 0
Email 91246 0
[email protected]
Contact person for public queries
Name 91247 0
Tongzhi Wu
Address 91247 0
Adelaide Medical School, the University of Adelaide, Level 5 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace, Adelaide, SA 5000
Country 91247 0
Australia
Phone 91247 0
+61 8 8313 6535
Fax 91247 0
Email 91247 0
[email protected]
Contact person for scientific queries
Name 91248 0
Tongzhi Wu
Address 91248 0
Adelaide Medical School, the University of Adelaide, Level 5 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace, Adelaide, SA 5000
Country 91248 0
Australia
Phone 91248 0
+61 8 8313 6535
Fax 91248 0
Email 91248 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.