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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] 262959 0
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 270683 0
Condition category
Condition code
Metabolic and Endocrine 270856 270856 0 0
Other metabolic disorders
Oral and Gastrointestinal 270857 270857 0 0
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] 269300 0
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] 279537 0
Gastric emptying.
Timepoint [1] 279537 0
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] 287862 0
Plasma Glucagon-Like Peptide-1 concentration.
Timepoint [1] 287862 0
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] 287863 0
Plasma Glucose-dependent Insulinotropic Peptide concentration.
Timepoint [2] 287863 0
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] 287864 0
Plasma glucagon concentration.
Timepoint [3] 287864 0
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] 287865 0
Glucose absorption.
Timepoint [4] 287865 0
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] 287866 0
Glucose.
Timepoint [5] 287866 0
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
Gender
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
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] 269764 0
Government body
Name [1] 269764 0
National Health and Medical Research Council
Address [1] 269764 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 269764 0
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] 268800 0
Individual
Name [1] 268800 0
Dr Adam Deane
Address [1] 268800 0
Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country [1] 268800 0
Australia
Secondary sponsor category [2] 268801 0
Individual
Name [2] 268801 0
Mr Thomas Crowhurst
Address [2] 268801 0
Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country [2] 268801 0
Australia
Secondary sponsor category [3] 268802 0
Individual
Name [3] 268802 0
Mr Matthew Summers
Address [3] 268802 0
Discipline of Acute Care Medicine
School of Medicine
Faculty of Health Sciences
University of Adelaide
North Terrace
Adelaide SA 5000
Country [3] 268802 0
Australia
Secondary sponsor category [4] 268803 0
Individual
Name [4] 268803 0
Professor Karen Jones
Address [4] 268803 0
Discipline of Medicine
School of Medicine
Faculty of Health Sciences
University of Adelaide
North Terrace
Adelaide SA 5000
Country [4] 268803 0
Australia
Secondary sponsor category [5] 268804 0
Individual
Name [5] 268804 0
Professor Juris Meier
Address [5] 268804 0
Head of Diabetes Research
Department of Medicine I
St. Josef Hospital
Ruhr University
44801 Bochum
Germany
Country [5] 268804 0
Germany
Secondary sponsor category [6] 268805 0
Individual
Name [6] 268805 0
Associate Professor Marianne Chapman
Address [6] 268805 0
Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country [6] 268805 0
Australia
Secondary sponsor category [7] 268806 0
Individual
Name [7] 268806 0
Associate Professor Christopher Rayner
Address [7] 268806 0
Discipline of Medicine
School of Medicine
Faculty of Health Sciences
University of Adelaide
North Terrace
Adelaide SA 5000
Country [7] 268806 0
Australia
Secondary sponsor category [8] 268807 0
Individual
Name [8] 268807 0
Professor Michael Horowitz
Address [8] 268807 0
Discipline of Medicine
School of Medicine
Faculty of Health Sciences
University of Adelaide
North Terrace
Adelaide SA 5000
Country [8] 268807 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271735 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 271735 0
Research Ethics Committee
Level 3 Hanson Institute
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Ethics committee country [1] 271735 0
Australia
Date submitted for ethics approval [1] 271735 0
Approval date [1] 271735 0
27/05/2011
Ethics approval number [1] 271735 0
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 33093 0
Address 33093 0
Country 33093 0
Phone 33093 0
Fax 33093 0
Email 33093 0
Contact person for public queries
Name 16340 0
Dr Mark Plummer
Address 16340 0
Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country 16340 0
Australia
Phone 16340 0
+61(0)402669167
Fax 16340 0
Email 16340 0
mark.philip.plummer@gmail.com
Contact person for scientific queries
Name 7268 0
Dr Mark Plummer
Address 7268 0
Intensive Care Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country 7268 0
Australia
Phone 7268 0
+61(0)402669167
Fax 7268 0
Email 7268 0
mark.philip.plummer@gmail.com

No information has been provided regarding IPD availability
Summary results
No Results