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Trial registered on ANZCTR


Registration number
ACTRN12614000986673
Ethics application status
Approved
Date submitted
20/08/2014
Date registered
12/09/2014
Date last updated
28/06/2021
Date data sharing statement initially provided
28/06/2021
Date results provided
28/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of recurrent hypoglycaemia on gastric emptying, glucose absorption, autonomic nerve function, cardiac function, glucagon, pancreatic polypeptide and catecholamine secretion.
Scientific title
The effects of recurrent hypoglycaemia in healthy males aged between 18 and 35 years on gastric emptying, glucose absorption, autonomic nerve function, cardiac function, glucagon, pancreatic polypeptide and catecholamine secretion.
Secondary ID [1] 285006 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 292516 0
Recurrent Hypoglycemia 292839 0
Gastric Emptying 292840 0
Autonomic Nerve Function 292841 0
Glucose Absorption 292842 0
Condition category
Condition code
Metabolic and Endocrine 292821 292821 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Antecedent hypoglycaemic episodes will be induced using a glucose-insulin clamp. An insulin infusion will be commenced based on body surface area at 125 mU/m^2/min then titrated over 10 minutes to a maintenance rate of 40mU/m^2/min and will remain constant for 60 mins. The rate of a concurrently run infusion of glucose (25%) will be varied to maintain blood glucose at the desired level. During this time blood glucose level will be monitored every 5 mins and every 15 mins following the hypoglycaemic episode. This will be repeated 4 times on the antecedent hypoglycaemic visit. Whereas during the euglycaemic visit there will only be one induced hypoglycaemic episode. Each visit will last approximately 27 hours and will take place at least 6 weeks apart.
Intervention code [1] 289841 0
Treatment: Drugs
Comparator / control treatment
Single hypoglycaemic episode during a 27 hour period
Control group
Active

Outcomes
Primary outcome [1] 292683 0
To measure whether antecedent episodes of insulin-induced hypoglycaemia attenuate the ‘normal’ acceleration of gastric emptying induced by hypoglycaemia, a mixed standardised meal (consisting of 100g minced beef (25g protein, 21g fat, ~270Kcal) will be labelled with 20 MBq 99mTechnitium-sulphur colloid. Scintigraphy (radioisotopic) data will be acquired in 1-min frames for 180-minutes.
Timepoint [1] 292683 0
Radioisotopic data will be acquired in 1-min frames for 180-minutes on two occasions on each study visit. This data will be collected at 0 and 24 hours when the test meal is given.
Secondary outcome [1] 309497 0
To determine whether antecedent episodes of insulin-induced hypoglycaemia attenuate the 'normal' increased rate of glucose absorption induced by hypoglycaemia. Blood will be sampled intravenously and glucose absorption will be assessed using plasma 3-O-methyl-D-gluco-pyranose (3-OMG). Blood (total 100ml) will be collected following the test meal (beef patty). Intravenous blood will be collected and centrifuged and the plasma will be stored at -80 degrees Celsius until analysed.
Timepoint [1] 309497 0
3-OMG samples will be taken every 15 minutes for the first hour and every half hour for the subsequent two hours during the scintigraphy.
Secondary outcome [2] 310029 0
To determine whether antecedent episodes of insulin-induced hypoglycaemia attenuate the 'normal' catecholamine, glucagon and pancreatic polypeptide secretion induced by hypoglycaemia. Intravenous blood will be collected, centrifuged and the plasma will be stored at -80 degrees Celsius until analysed for catecholamines, glucagon and pancreatic polypeptide.
Timepoint [2] 310029 0
Intravenous blood will be taken for catecholamines, glucagon and pancreatic polypeptide at 30 mins intervals for an hour (T=-15, 15, 30) during each clamp (hypoglycaemic/euglycaemic episode).
Secondary outcome [3] 310369 0
To determine whether antecedent episodes of hypoglycaemia effects autnonomic nerve function. Autonomic nerve function will be examined using blood pressure and electrocardiogram data (using R-R interval change in response to deep breathing).
Timepoint [3] 310369 0
Autonomic Nerve function will be assessed twice on each study visit during the first and fourth clamp.
Secondary outcome [4] 310371 0
To determine whether antecedent episodes of hypoglycaemia effects cardiac function. Cardiac function will be assessed using a 12 lead ECG will be performed twice on each study visit and 4-chamber view echocardiography, which will be performed every 30 mins during each clamp.
Timepoint [4] 310371 0
Cardiac function will be assessed twice on each study visit during the first and fourth clamp.

Eligibility
Key inclusion criteria
Healthy lean (BMI 18-30) young men aged 18-35
Minimum age
18 Years
Maximum age
35 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria will comprise:
*Radiation exposure for research purposes in the past 12 months;
*History of diabetes;
*HbA1c >6.0%;
*Impaired renal function;
*Creatinine clearance <100 ml/min;
*Hb <130 g/L
*Taking medication that are known to effect gastrointestinal motility;
*Taking medication effecting blood glucose;
*Previous surgery on the stomach or small intestine;
*History of autonomic neuropathy;
*Smoking >10 cigarettes per day;
*Alcohol >20g per day;
*History of cardiac disease ;
*History of cardiac arrhythmias;
*ECG abnormalities;
*Because of concerns of cumulative life time exposure to radiation, we will directly screen all volunteers as to their previous radiation exposure, and will exclude any volunteer who has received 3 or more examinations using a computerized tomogram and/or 10 or more examinations using standard x-rays.
*Previous surgery on the autonomic nervous system (eg sympathectomy)
*Previous surgery on the adrenal glands
*History of seizures or seizure disorders
*History of migranes

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 enrolled using an enrollment number and data will be sent to the Royal Adelaide Hospital clinical trials pharmacy department to be randomised for drug treatments.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be completed by the clinical trials pharmacy
department using a randomisation table created by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
The participant number for this study was determined based on statistical power from previous studies. Clinical and statistical assumptions for this study is based on Plummer et al. 2014 (Glucagon-like peptide 1 attenuates the acceleration of gastric emptying induced by hypoglycemia in healthy subjects; Diabetes Care) which assessed similar outcomes (P<0.001). The sample size of 15 healthy volunteers was selected based on a power calculation using this data. We believe that 15 volunteers will have the statistical power required to detect a significant difference between the groups (P<0.05). Outcome variables will be analysed using an appropriate statistical methods.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
22/09/2014
Actual
8/12/2014
Date of last participant enrolment
Anticipated
20/01/2016
Actual
5/01/2015
Date of last data collection
Anticipated
Actual
16/02/2016
Sample size
Target
15
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 2735 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 8449 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 289621 0
Government body
Name [1] 289621 0
National Health and Medical Research Council Grant
Country [1] 289621 0
Australia
Primary sponsor type
Individual
Name
Associate Professor Adam Deane
Address
Intensive Care Unit, Royal Adelaide Hospital
North Terrace
Adelaide 5000
South Australia
Country
Australia
Secondary sponsor category [1] 288309 0
None
Name [1] 288309 0
Address [1] 288309 0
Country [1] 288309 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291541 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 291541 0
Ethics committee country [1] 291541 0
Australia
Date submitted for ethics approval [1] 291541 0
Approval date [1] 291541 0
08/08/2014
Ethics approval number [1] 291541 0
140605

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49846 0
Dr Palash Kar
Address 49846 0
Royal Adelaide Hospital
North Terrace
Adelaide 5000
South Australia
Country 49846 0
Australia
Phone 49846 0
+6188222 4624
Fax 49846 0
Email 49846 0
p_kar@hotmail.com
Contact person for public queries
Name 49847 0
Palash Kar
Address 49847 0
Royal Adelaide Hospital
North Terrace
Adelaide 5000
South Australia
Country 49847 0
Australia
Phone 49847 0
+6188222 4624
Fax 49847 0
Email 49847 0
p_kar@hotmail.com
Contact person for scientific queries
Name 49848 0
Palash Kar
Address 49848 0
Royal Adelaide Hospital
North Terrace
Adelaide 5000
South Australia
Country 49848 0
Australia
Phone 49848 0
+6188222 4624
Fax 49848 0
Email 49848 0
p_kar@hotmail.com

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?

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
SourceTitleYear of PublicationDOI
EmbaseAntecedent hypoglycemia does not attenuate the acceleration of gastric emptying by hypoglycemia.2017https://dx.doi.org/10.1210/jc.2017-00051
N.B. These documents automatically identified may not have been verified by the study sponsor.