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Trial registered on ANZCTR


Registration number
ACTRN12613001384741
Ethics application status
Approved
Date submitted
16/07/2013
Date registered
17/12/2013
Date last updated
10/11/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of Glucagon-Like Peptide-1 (GLP-1) administration on gastric emptying during periods of hyperglycaemia in healthy volunteers.
Scientific title
Effects of exogenous Glucagon-Like Peptide-1 (GLP-1) administration on gastric emptying during hyperglycaemic clamp experiments in healthy volunteers.
Secondary ID [1] 282834 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glycaemic control and gastric emptying 289631 0
Condition category
Condition code
Metabolic and Endocrine 289955 289955 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each volunteer will be studied on 4 occasions separated by a minimum of 1 week. Each subject will receive intravenous infusions (over 4.5 hours) of (i) GLP-1 at 0.9 pmol/kg/min, or (ii) 0.9% isotonic saline. For both GLP-1 and control, blood glucose will be maintained at either (i) hyperglycaemia (15mmol/l) or (ii) euglycaemia (~6mmol/l) using a glucose infusion clamp.
Intervention code [1] 287524 0
Treatment: Drugs
Comparator / control treatment
The control will be a placebo of 0.9% isotonic saline
Control group
Placebo

Outcomes
Primary outcome [1] 290009 0
Gastric emptying will be assessed via Scinitgraphy
Timepoint [1] 290009 0
Gastric emptying will be measured for four hours from t=30 min to t=4.5 hours.
Secondary outcome [1] 303767 0
Glucose absorption will be measured using 3-OMG concentrations.
Timepoint [1] 303767 0
Blood samples for hormone concentrations will be taken every 15 minutes, from t=0 to t=4.5.
Secondary outcome [2] 303806 0
Plasma concentrations of GIP, GLP-1 and glucagon will be measured
Timepoint [2] 303806 0
Blood samples for hormone concentrations will be taken every 15 minutes, from t=0 to t=4.5.
Secondary outcome [3] 303807 0
The amount of IV glucose used to maintain glycaemia will also be recorded
Timepoint [3] 303807 0
This will be the total glucose infused during the glycaemic clamp (4.5 hours).
Secondary outcome [4] 305674 0
Blood glucose concentrations
Timepoint [4] 305674 0
Blood glucose will be monitored every 5 minutes from t=0 min to t=2 hours. Blood glucose will be monitored every 15 minutes from t=2 hours to t=4.5 hours

Eligibility
Key inclusion criteria
15 healthy volunteers, with no history of diabetes, minimal alcohol and nicotine consumption and BMI <32, aged 50-80 years
Minimum age
50 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria will comprise
- Inability to give informed consent
- Known diabetes mellitus or a glycated haemoglobin (HbA1c) >/=6.5%
- Abnormal ferritin levels, haemoglobin levels or liver function on screening
- Previous gastrointestinal surgery
- Taking medications known to affect gastrointestinal motility or blood sugar.
This includes: insulin, oral hypoglycaemic agents (metformin, sulphonylureas, acarbose), antibiotics, steroids, proton pump inhibitors, amtiemetics, prokinetic agents and H2 receptor antagonists.
- Body Mass Index >32kg/m2
- Smoking >10 cigarettes/day
- Alcohol consumption >20g/day
- Previous exposure to radiation for research purposes in the preceding 12 months
- Volunteers who have donated blood in the preceding 3 months
- Female volunteers of child bearing age who are pregnant or lactating, or who have inadequate contraception
- Suffer from any chronic medical condition such as (but not limited to) heart failure, ischaemic heart disease, chronic lung disease, autonomic dysfunction resulting from any cause, active or previously treatment malignancy, chronic infections (e.g. viral hepatitis and HIV)
- Taking any prescription or over the counter medications other than simple analgesics (e.g. paracetamol)
- Suffered from any acute medical illness (e.g. upper respiratory tract infection, pneumonia...etc) during the 4 week period before recruitment

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)
Participants will be given an enrollment number and this will be used by pharmacy to provide 4 blinded treatments
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation is performed by the clinical trials pharmacy department. They use 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
Crossover
Other design features
Patients will act as their own controls
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
Outcome variables will be analysed using an appropriate statistical methods. Data will be presented and analysed using parametric and/or non-parametric approaches as appropriate based on distribution of data. The results will be analysed and submitted for publication in an international peer-reviewed journal.

Previous studies by our group have shown that the gastrokinetic effects of drugs are substantially altered by changes in glycaemia. In this study we wish to determine the pairwise difference between the four study days as the primary endpoint. However, it would be of substantial interest to estimate the interaction between glycaemia and GLP-1. In particular to compare (i) placebo-hyperglycaemia vs. GLP-1 hyperglycaemia (ii) GLP-normoglycaemia vs. GLP-1-hyperglycaemia. Given the complexity of the power calculation we have discussed the sample size with a biostatistician. With a sample sizes of 10 the minimum detectable differences is 9 minutes. This is using a significance level of 0.01 to account for an adjustment for multiple post-hoc testing across the other comparisons that we are interested in.

Recruitment
Recruitment status
Completed
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)
SA
Recruitment hospital [1] 1279 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 7164 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 287614 0
Government body
Name [1] 287614 0
National Health and Medical Research Council Funding grant
Address [1] 287614 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 287614 0
Australia
Primary sponsor type
Individual
Name
Dr Mark Plummer
Address
Royal Adelaide Hospital
North Terrace
Adelaide
SA 5000
Country
Australia
Secondary sponsor category [1] 286358 0
Individual
Name [1] 286358 0
Dr Adam Deane
Address [1] 286358 0
Royal Adelaide Hospital
North Terrace
Adelaide
SA 5000
Country [1] 286358 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289584 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 289584 0
Royal Adelaide Hospital
North Terrace
Adelaide
SA 5000
Ethics committee country [1] 289584 0
Australia
Date submitted for ethics approval [1] 289584 0
Approval date [1] 289584 0
04/07/2013
Ethics approval number [1] 289584 0
130416

Summary
Brief summary
The major mechanism of action of GLP-1 agonists in lowering post-prandial glycaemia is their ability to slow gastric emptying. Acute hyperglycaemia itself is known to slow gastric emptying substantially and it is likely that many patients will be hyperglycaemic at the time of GLP-1 administration. If GLP-1 does not further slow gastric emptying during marked hyperglycaemia then it is likely the agonists will have only a minimal effect to attenuate postprandial glycaemia. The latter observation would support a rationale to reserve GLP-1 agonists until fasting glycaemia is reduced, eg. by initial insulin therapy, whereas if the hypothesis is rejected then GLP-1 agonists would be a rational choice as single agents even in patients with marked fasting hyperglycaemia. Accordingly, it is important to determine whether hyperglycaemia per se affects the capacity for GLP-1 to slow gastric emptying.
Trial website
Trial related presentations / publications
Plummer MP, Jones KL, Cousins CE, Trahair LG, Meier JJ, Chapman MJ, Horowitz M, Deane AM.Hyperglycemia potentiates the slowing of gastric emptying induced by exogenous GLP-1. Diabetes Care. 2015 Jun;38(6):1123-9.
.
Public notes

Contacts
Principal investigator
Name 41450 0
Dr Mark Plummer
Address 41450 0
ICU Research
Royal Adelaide Hospital
North Terrace
Adelaide
SA 5000
Country 41450 0
Australia
Phone 41450 0
61882224624
Fax 41450 0
Email 41450 0
mark.philip.plummer@gmail.com
Contact person for public queries
Name 41451 0
Dr Mark Plummer
Address 41451 0
ICU Research
Royal Adelaide Hospital
North Terrace
Adelaide
SA 5000
Country 41451 0
Australia
Phone 41451 0
61882224624
Fax 41451 0
Email 41451 0
mark.philip.plummer@gmail.com
Contact person for scientific queries
Name 41452 0
Dr Mark Plummer
Address 41452 0
ICU Research
Royal Adelaide Hospital
North Terrace
Adelaide
SA 5000
Country 41452 0
Australia
Phone 41452 0
61882224624
Fax 41452 0
Email 41452 0
mark.philip.plummer@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary