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Trial registered on ANZCTR

Registration number

ACTRN12611000973910

Ethics application status

Approved

Date submitted

31/08/2011

Date registered

12/09/2011

Date last updated

5/06/2018

Type of registration

Retrospectively registered

Titles & IDs

Public title

The effects of Glucagon-Like Peptide 1 on gastric emptying in healthy volunteers with normal or low blood glucose levels

Scientific title

A study of healthy volunteers receiving exogenous Glucagon-Like Peptide-1 or placebo during euglycaemia or hypoglycaemia and effects on gastric emptying

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Gastric emptying in the context of supraphysiologic Glucagon-Like Peptide-1 and hypoglycaemia

Condition category

Condition code

Metabolic and Endocrine

Other metabolic disorders

Oral and Gastrointestinal

Normal oral and gastrointestinal development and function

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

There are two interventions in the trial.

The first intervention is intravenous Glucagon-Like Peptide-1 (1.2 pmol/kg/min) or placebo (normal saline infused at 1 ml/min). The pharmacy at the Royal Adelaide Hospital randomises the volunteers to product or placebo on each occasion and also conducts the blinding.

The second intervention is the glycaemia of the volunteers, being either euglycaemia (target blood glucose concentration of 6.0 mmol/l) or hypoglycaemia (target blood glucose concentration of 2.6 mmol/l). This is achieved through administering an intravenous insulin infusion at previously validated rate plus a simultaneous intravenous 25% glucose infusion titratedf to the target glycaemia. There is no blinding to the glycaemia of the patient.

Each patient undergoes 4 different experiments in the trial, being as follows:

1. Euglycaemia and GLP-1;
2. Euglycaemia and placebo;
3. Hypoglycaemia and GLP-1; and
4. Hypoglycaemia and placebo.

This ensures that each of the four possible combinations of interventions is covered by each participant. As noted earlier, the order of combinations 1 and 2 is randomised, as is the order of combinations 3 and 4. Each study day is separated by a minimum of 4 days.

The protocol for the study begins at t = -60, when the GLP-1 / placebo infusion is initiated. The glucose-insulin clamp is started at t = -30 and achieved by t = -15. The test meal and drink are consumed at t = 0. If the study is a hypoglycaemic study, the clamp is continued until t = 45, when the target blood glucose concentration is increased back to euglycaemia (6.0 mmol/l). Measurements are taken until the study concludes at t = 180.

The standardised test meal is 100 grams of minced beef containing 20 MBq of 99m Technetium-sulphur-colloid. This is utilised to enable a gamma camera to measure gastric emptying. The standardised test drink is 150 ml of water containing 3 grams of 3-O-methyl-D-gluco-pyranose. This is a glucose analogue that is absorbed across the intestinal wall in the same way as glucose but which is not hepatically metabolised and is renally cleared. Blood concentrations of 3-O-methyl-D-gluco-pyranose are used to assess glucose absorption. These are both consumed in all studies at t = 0.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

As described above, the 'control' studies are:

2. Euglycaemia and placebo; and
4. Hypoglycaemia and placebo.

The protocol for these experiments is described above. Each patient thereby acts as their own control, by participating in all four of the possible combinations of the two interventions (and their associated 'control' / placebo arms).

Control group

Placebo

Outcomes

Primary outcome [1]

Gastric emptying.

Timepoint [1]

Measured by radioisotopic gamma camera. This camera takes frames every 1 minute for the first 60 minutes and then every 3 minutes for the remaining 120 minutes. The recording begins at t = 0 (the time at which the meal and drink are consumed) and continues until t = 180.

Secondary outcome [1]

Plasma Glucagon-Like Peptide-1 concentration.

Timepoint [1]

Measured by enzyme-linked immunosorbent assay (Epitope diagnostics, United Kingdom). Blood is collected to measure the concentration of this hormone at t = -60 and t = -30 minutes. Collections are then taken every 15 minutes from t = 0 to t = 60 minutes and subsequently every 30 minutes for the remaining 120 minutes.

Secondary outcome [2]

Plasma Glucose-dependent Insulinotropic Peptide concentration.

Timepoint [2]

Measured by Gut Hormone Milliplex Kit (Millipore, Billerica, Massachusetts). Blood is collected to measure the concentration of this hormone at t = -60 and t = -30 minutes. Collections are then taken every 15 minutes from t = 0 to t = 60 minutes and subsequently every 30 minutes for the remaining 120 minutes.

Secondary outcome [3]

Plasma glucagon concentration.

Timepoint [3]

Measured by radioimmunoassay. Blood is collected to measure the concentration of this hormone at t = -60 and t = -30 minutes. Collections are then taken every 15 minutes from t = 0 to t = 60 minutes and subsequently every 30 minutes for the remaining 120 minutes.

Secondary outcome [4]

Glucose absorption.

Timepoint [4]

Measured by determination of absorption of 3-O-methyl-D-gluco-pyranose concentration through High Performance Liquid Chromatography. Blood is collected to measure the concentration of this agent every 15 minutes from t = 15 minutes to t = 60 minutes. Subsequently collections are made every 30 minutes for the remaining 120 minutes.

Secondary outcome [5]

Glucose.

Timepoint [5]

Blood glucose concentration is measured using a portable glucometer at the beginning of the study. It is measured every 5 minutes from t = -30 minutes to t = 90 minutes. It is then measured every 15 minutes for the remaining 90 minutes. These recordings are validated against measurements via venous blood gas analysis, which are taken every 15 minutes from t = -30 to t = 90. They are then taken every 30 minutes until t = 180.

Eligibility

Key inclusion criteria

Healthy volunteer between 50 and 80 years of age.

Minimum age

50 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

- Unable to give informed consent;
- Vegetarian (as the study involves the consumption of a beef meal);
- Diabetes mellitus;
- Glycated haemoglobin (HbA1c) > 6.5%;
- Migraine or seizure disorder;
- Anormal ferritin or haemoglobin levels;
- Abnormal liver function test results;
- Previous gastrointestinal surgery;
- Receiving medication(s) that affect gastrointestinal motility or blood sugar;
- Body Mass Index >32 kg/m2;
- Smoking >10 cigarettes/day;
- Alcohol consumption >20 g/day;
- Previous exposure to radiation for research purposes in the preceding 12 months;
- Donation of blood in the preceding 3 months;
- Female volunteers of child bearing age who are pregnant, lactating or who have inadequate contraception.

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)

This is a double-blind randomised cross-over study in which the volunteers act as their own controls. Each volunteer undergoes four studies where they receive either intravenous product (Glucagon-Like Peptide-1 at 1.2 pmol/kg/min) or placebo (0.9% normal saline at 1 ml/min) during either hypoglycaemia (2.6 mmol/l) or euglycaemia (6.0 mmol/l). The blinding of the product / placebo is conducted by the pharmacy at our institution. The bags for intravenous solution are blinded using a black coating.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

The pharmacy uses a computerised randomisation system to allocate patients to product or placebo on each treatment day.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Crossover

Other design features

Phase

Phase 2

Type of endpoint/s

Pharmacodynamics

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

9/08/2011

Actual

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)

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Individual

Name

Dr Mark Plummer

Address

Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Dr Adam Deane

Address [1]

Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000

Country [1]

Australia

Secondary sponsor category [2]

Individual

Name [2]

Mr Thomas Crowhurst

Address [2]

Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000

Country [2]

Australia

Secondary sponsor category [3]

Individual

Name [3]

Mr Matthew Summers

Address [3]

Discipline of Acute Care Medicine
School of Medicine
Faculty of Health Sciences
University of Adelaide
North Terrace
Adelaide SA 5000

Country [3]

Australia

Secondary sponsor category [4]

Individual

Name [4]

Professor Karen Jones

Address [4]

Discipline of Medicine
School of Medicine
Faculty of Health Sciences
University of Adelaide
North Terrace
Adelaide SA 5000

Country [4]

Australia

Secondary sponsor category [5]

Individual

Name [5]

Professor Juris Meier

Address [5]

Head of Diabetes Research
Department of Medicine I
St. Josef Hospital
Ruhr University
44801 Bochum
Germany

Country [5]

Germany

Secondary sponsor category [6]

Individual

Name [6]

Associate Professor Marianne Chapman

Address [6]

Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000

Country [6]

Australia

Secondary sponsor category [7]

Individual

Name [7]

Associate Professor Christopher Rayner

Address [7]

Discipline of Medicine
School of Medicine
Faculty of Health Sciences
University of Adelaide
North Terrace
Adelaide SA 5000

Country [7]

Australia

Secondary sponsor category [8]

Individual

Name [8]

Professor Michael Horowitz

Address [8]

Discipline of Medicine
School of Medicine
Faculty of Health Sciences
University of Adelaide
North Terrace
Adelaide SA 5000

Country [8]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Adelaide Hospital Research Ethics Committee

Ethics committee address [1]

Research Ethics Committee
Level 3 Hanson Institute
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

27/05/2011

Ethics approval number [1]

110516

Summary

Brief summary

This study aims to determine the effects of Glucagon-Like Peptide-1 (a hormone) on gastric (stomach) emptying in heathly volunteers with normal and low blood sugar levels. 

In particular, the study aims to answer the question: does the slowing of stomach emptying caused by Glucagon-Like Peptide-1 persist even when a person has low blood sugar levels? 

The 'null hypothesis' is that the effects of Glucagon-Like Peptide-1 on gastric emptying will be unaffected by blood sugar levels.

This study is important because important safety implications arise from the relationship between slowed gastric emptying caused by Glucagon-Like Peptide-1 and blood sugar levels. If a patient is receiving Glucagon-Like Peptide-1 as a therapy for Type II Diabetes Mellitus and also develops low blood sugar levels, then the rate his / her stomach empties is important for the correction of the low blood sugar levels.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Dr Mark Plummer

Address

Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000

Country

Australia

Phone

+61(0)402669167

Fax

[email protected]

Contact person for scientific queries

Name

Dr Mark Plummer

Address

Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000

Country

Australia

Phone

+61(0)402669167

Fax

[email protected]

No information has been provided regarding IPD 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

Source	Title	Year of Publication	DOI
Dimensions AI	Dysglycaemia in the critically ill and the interaction of chronic and acute glycaemia with mortality	2014	https://doi.org/10.1007/s00134-014-3287-7
Embase	Hyperglycemia potentiates the slowing of gastric emptying induced by exogenous GLP-1.	2015	https://dx.doi.org/10.2337/dc14-3091

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically