Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001506785
Ethics application status
Approved
Date submitted
21/02/2022
Date registered
2/12/2022
Date last updated
2/12/2022
Date data sharing statement initially provided
2/12/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Do short acting glucagon-like receptor agonists (GLP-1 RAs) attenuate the acceleration of gastric emptying induced by hypoglycaemia in type 2 diabetes?
Scientific title
Do short acting glucagon-like receptor agonists (GLP-1 RAs) attenuate the 'gastric' counter-regulatory response to hypoglycaemia in type 2 diabetes?
Secondary ID [1] 306489 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 325353 0
Condition category
Condition code
Metabolic and Endocrine 322737 322737 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Short acting GLP-1 receptor agonist, exenatide twice daily OR placebo
a) exenatide dose 10microgram twice daily
b) duration of administration: 4 weeks - drug and 4 weeks - placebo
c) Mode of administration - subcutaneous injection
d) monitoring adherence - frequent phone calls during trial period to ensure compliance, checking the number of injections left when participant attends study day at the end of each 4 week period.
Intervention code [1] 322916 0
Treatment: Drugs
Comparator / control treatment
The placebo vial contains normal saline only. Placebo vial prepared by the Royal Adelaide Hospital Pharmacy specifically for this trial.
Control group
Placebo

Outcomes
Primary outcome [1] 330540 0
The primary outcome will be the change in the gastric emptying between hypoglycaemia and euglycaemia after 4 weeks treatment with exenatide BID vs Placebo treatment for 4 weeks.
Gastric emptying will be assessed by scintigraphy (gamma camera) - this is the gold standard technique.
Timepoint [1] 330540 0
Gastric emptying T100 (T100 is the gastric retention at 100 minutes)

Gastric emptying will be assessed 4 times i.e 4 separate days in total (twice after 4 weeks of exenatide treatment and twice after 4 weeks of placebo) during the trial
Secondary outcome [1] 406566 0
The secondary outcomes will be differences in plasma catecholamines between hypoglycaemia and euglycaemia study days
Timepoint [1] 406566 0
Plasma catecholamine will be measured at t = -15, 15, 30, 75, 90, 120, 150, and 180 min during the clamp studies.
The clamp studies will occur 4 times in total (twice after 4 weeks of exenatide treatment and twice after 4 weeks of placebo) during the trial
Secondary outcome [2] 416324 0
The additional secondary outcomes will be differences in plasma 3-OMG between hypoglycaemia and euglycaemia study days
Timepoint [2] 416324 0
Plasma 3-OMG will be measured at t = -15, 15, 30, 75, 90, 120, 150, and 180 min during the clamp studies.
The clamp studies will occur 4 times in total (twice after 4 weeks of exenatide treatment and twice after 4 weeks of placebo) during the trial

Eligibility
Key inclusion criteria
• Men and women with type 2 diabetes either diet controlled or metformin alone
• Aged 40 - 70 years
• Body Mass Index 20-40 kg/m²
• HbA1c less than or equal to 8.5 %
Minimum age
40 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of type 1 diabetes or on medications other than metformin
• HbA1c >8.5 %
• History of gastrointestinal disease, including known gastroparesis, peptic ulcer disease, significant upper or lower gastrointestinal symptoms, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy) or a history of migraine or panic attacks.
• Other significant illness, including epilepsy, cardiovascular or respiratory disease.
• Impaired renal function (as assessed by calculated creatinine clearance < 50 mL/min using the Cockcroft-Gault equation) or if iron stores or liver function tests are outside the following normal ranges:
- Alanine aminotransferase (ALT) < 110 U/L
- Alkaline phosphatase (ALP) 30 - 110 U/L
- Aspartate transaminase (AST) < 90 U/L
- Total bilirubin 2 - 24 µmol/L
- Haemoglobin 130 – 180 g/L (Males)
- Haemoglobin 115 – 155 g/L (Females)
- Ferritin > 30 µg/L (Males)
- Ferritin > 15 µg/L
(Females)
• Requirement for medication known to influence gastrointestinal function, (e.g. prokinetic drugs [metoclopramide, domperidone, erythromycin], antiemetics [ondansetron], antidiarrhoeals [loperamide], H2 receptor antagonists [ranitidine], drugs with substantial anticholinergic effects [amitriptyline, doxepin, dothiepin, mirtazapine, haloperidol, chlorpromazine, risperidone, oxybutynin], opioids [morphine, oxycodone, codeine], orlistat.
• Evidence of drug or alcohol abuse, or consumption of more than 20 g alcohol or 10 cigarettes on a daily basis.
• Vegetarian
• Donation of blood within the previous 3 months
• Participation in any other research studies within the previous 3 months
• Previous exposure to radiation for research purposes in the preceding 12 months
• Inability to give informed consent
• Positive pregnancy status or lactating (breast-feeding) female
• Contra-indication to use of exenatide
• A known history of intolerance or unwilling to self-inject exenatide

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
22/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 21793 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 36850 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 310835 0
Hospital
Name [1] 310835 0
RAH Clinical Grants
Country [1] 310835 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Royal Adelaide Hospital, Port Rd, Adelaide SA 5005
Country
Australia
Secondary sponsor category [1] 312089 0
None
Name [1] 312089 0
none
Address [1] 312089 0
none
Country [1] 312089 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310400 0
CALHN Human Research Ethics Committee
Ethics committee address [1] 310400 0
level 3, Roma Mitchell House, 136 North Terrace, Adelaide, South Australia SA 5000
Ethics committee country [1] 310400 0
Australia
Date submitted for ethics approval [1] 310400 0
Approval date [1] 310400 0
15/01/2020
Ethics approval number [1] 310400 0

Summary
Brief summary
Gastric emptying (GE), which exhibits a wide inter-individual variation, determines the rate of exposure of nutrients (including carbohydrates) to the small intestine, where they are absorbed into the circulation. Insulin-induced hypoglycaemia (~2.5 mmol/L) accelerates gastric emptying substantially in both health and diabetes. The major mechanism for lowering of postprandial glycaemia by GLP-1 receptor agonists is by slowing gastric emptying. Although GLP-1RAs themselves are associated with minimal risk of hypoglycaemia (since their insulinotropic effects are glucose-dependent), the risk of hypoglycaemia is increased substantially when GLP-1RAs, especially short-acting, are combined with exogenous insulin or insulin secretagogues. Our aim is to determine whether treatment with short-acting GLP-1RAs, attenuates the acceleration of gastric emptying during insulin-induced hypoglycaemia in patients with type 2 diabetes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117526 0
Dr Chinmay Marathe
Address 117526 0
Work Organisation: University of Adelaide
Level 5, AHMS Building, North Terrace, Adelaide SA 5000
Country 117526 0
Australia
Phone 117526 0
+61 431266075
Fax 117526 0
Email 117526 0
chinmay.marathe@adelaide.edu.au
Contact person for public queries
Name 117527 0
Dr Chinmay Marathe
Address 117527 0
Work Organisation: University of Adelaide
Level 5, AHMS Building, North Terrace, Adelaide SA 5000
Country 117527 0
Australia
Phone 117527 0
+61 431266075
Fax 117527 0
Email 117527 0
chinmay.marathe@adelaide.edu.au
Contact person for scientific queries
Name 117528 0
Dr Chinmay Marathe
Address 117528 0
Work Organisation: University of Adelaide
Level 5, AHMS Building, North Terrace, Adelaide SA 5000
Country 117528 0
Australia
Phone 117528 0
+61 431266075
Fax 117528 0
Email 117528 0
chinmay.marathe@adelaide.edu.au

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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15181Ethical approval    383617-(Uploaded-21-02-2022-13-28-42)-Study-related document.pdf
15183Informed consent form    383617-(Uploaded-21-02-2022-13-34-26)-Study-related document.pdf



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.