ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Diabetes

Condition category

Condition code

Metabolic and Endocrine

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]

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]

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]

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]

The secondary outcomes will be differences in plasma catecholamines between hypoglycaemia and euglycaemia study days

Timepoint [1]

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]

The additional secondary outcomes will be differences in plasma 3-OMG between hypoglycaemia and euglycaemia study days

Timepoint [2]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment postcode(s) [1]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

RAH Clinical Grants

Address [1]

Royal Adelaide Hospital, Port Rd, Adelaide SA 5005

Country [1]

Australia

Primary sponsor type

Hospital

Name

Royal Adelaide Hospital

Address

Royal Adelaide Hospital, Port Rd, Adelaide SA 5005

Country

Australia

Secondary sponsor category [1]

None

Name [1]

none

Address [1]

none

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

CALHN Human Research Ethics Committee

Ethics committee address [1]

level 3, Roma Mitchell House, 136 North Terrace, Adelaide, South Australia SA 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

15/01/2020

Ethics approval number [1]

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

Dr Chinmay Marathe

Address

Work Organisation: University of Adelaide
Level 5, AHMS Building, North Terrace, Adelaide SA 5000

Country

Australia

Phone

+61 431266075

Fax

chinmay.marathe@adelaide.edu.au

Contact person for public queries

Name

Chinmay Marathe

Address

Work Organisation: University of Adelaide
Level 5, AHMS Building, North Terrace, Adelaide SA 5000

Country

Australia

Phone

+61 431266075

Fax

chinmay.marathe@adelaide.edu.au

Contact person for scientific queries

Name

Chinmay Marathe

Address

Work Organisation: University of Adelaide
Level 5, AHMS Building, North Terrace, Adelaide SA 5000

Country

Australia

Phone

+61 431266075

Fax

chinmay.marathe@adelaide.edu.au

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?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
15181	Ethical approval					383617-(Uploaded-21-02-2022-13-28-42)-Study-related document.pdf
15183	Informed 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.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically