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Trial registered on ANZCTR


Registration number
ACTRN12617000512325
Ethics application status
Approved
Date submitted
29/03/2017
Date registered
7/04/2017
Date last updated
18/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Continuous glucose monitoring system used to establish medication management protocol for the safe use of a 2-day intermittent energy restriction (5:2 diet) in type 2 diabetes mellitus.
Scientific title
The effects of fixed compared to adjusted medication protocol using continuous glucose monitoring system for the safe use of a 2-day intermittent energy restriction in type 2 diabetes mellitus.
Secondary ID [1] 291585 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 302700 0
Obesity 302736 0
Condition category
Condition code
Diet and Nutrition 302214 302214 0 0
Obesity
Metabolic and Endocrine 302215 302215 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A randomised controlled trial will be conducted to test two medication protocols; fixed and adjusted (see below). Based on the binomial data (number of hypo/hyperglycaemic events after 2 weeks of treatment in our pilot trial), a sample size of 40 participants who are already experiencing hypoglycaemic events will be required to demonstrate superiority. We aim to recruit 50 participants in case of dropouts.
Participants with a BMI>27 and medication controlled T2DM, both oral hypoglycaemic agents (OHA) likely to cause hypoglycaemia (sulphonylureas) and insulin, will attend the clinic at baseline to have their continuous glucose monitoring system (CGMS) sensor installed and baseline HbA1c measured. The sensor has a 5mm flexible filament that is inserted, subcutaneously, into the back of the upper arm, (there may be a small amount of discomfort). The sensor starts recording blood glucose levels 1 hour after insertion. HbA1c will be measured using a point of care machine which requires finger prick blood only. Participants will then be asked to follow their usual diet for 2 weeks, recording their intake (weighed diet record) and using the monitor to store continuous glucose data. (The electronic monitor records and stores BGLs from the sensor electrode. Participants will be required to scan their sensor every 6-8 hours to record continuous data). The data will allow us to establish the regularity of extreme levels and the number of events; hypoglycaemic events <4mmol/L and/or hyperglycaemia events >10mmol/L. Participants will then attend the clinic for a second visit (after 2 weeks) to have their original sensor removed and the data analysed. If the participant experiences 1 or more hypoglycaemic events they will be eligible to continue into the intervention phase.

Eligible participants will attend for a third visit to have a new sensor installed and to start the intervention, 2 weeks of 2-day IER treatment (500-600kcals/day) (non-consecutive) with their specific medication protocol; randomised 1:1 to either fixed or adjusted medication treatment groups. A Dietitian with 5+ years clinical experience and an Endocrinologist with 10+ years clinical experience will be conducting the research (providing dietary advice, including a written IER treatment booklet designed for this study with diet details and delivering the medication protocol). During the intervention period, participants will continue to record dietary intake and use the monitor to store continuous glucose data. Participants will be asked to keep their diet on habitual eating days similar to the previous fortnights intake. Participants will then attend the clinic for their final visit at the end of their 2-week period to have their sensor removed. We will then analyse the intervention CGMS data to see if glucose control improved (reduced number of events) due to the adjusted medication protocol. Participants will be asked to keep their exercise levels stable during the 4-5 week trial, pedometers will be provided.

Adjusted protocol is based on the number of glycaemic events during the participants 2 week usual/normal diet.
One or more hypoglycaemic events over 2 weeks then follow the fixed protocol 1 level greater restriction than appropriate. E.G: If HbA1c is >=7% then the participant should follow the <7% fixed protocol (see details in fixed protocol below).
Four or more events over 2 weeks then follow protocol 1 level less restriction than appropriate. E.G: If HbA1c is <7% then the participant should follow the >=7-<8% fixed protocol (see details in fixed protocol below).
Hypoglycaemia takes priority.
Note: if participants experience no hypo or hyper glycaemic events over 2 weeks they will follow the fixed protocol for their HbA1c level.

Fixed protocol.
Our fixed protocol requires discontinuation of sulphonylureas as well as insulin if baseline HbA1c is <7%.
If >=7 but <8% then sulphonylureas are discontinued on intermittent energy days only and long acting insulin the night before the intermittent energy day.
If HbA1c is >=8% but <10% then all medications are discontinued on intermittent energy days only.
If HbA1c is >= 10% but <12% then sulphonylureas remain unchanged, short active insulin is discontinued and long acting insulin is reduced by 10% on intermittent energy days only.
If >=12% then short acting insulin is discontinued on intermittent energy days only.
Intervention code [1] 297653 0
Treatment: Other
Intervention code [2] 297687 0
Treatment: Devices
Comparator / control treatment
Fixed: Medication protocol previously established in our published research.
Intermittent energy restriction in type 2 diabetes: A short
discussion of medication management. DOI: 10.4239/wjd.v7.i20.627

Our fixed protocol requires discontinuation of sulphonylureas as well as insulin if baseline HbA1c is <7%. If >=7 but <8% then sulphonylureas are discontinued on intermittent energy days only and long acting insulin the night before the intermittent energy day. If HbA1c is >=8% but <10% then all medications are discontinued on intermittent energy days only. If HbA1c is >= 10% but <12% then sulphonylureas remain unchanged, short active insulin is discontinued and long acting insulin is reduced by 10% on intermittent energy days only. If >=12% then short acting insulin is discontinued on intermittent energy days only.
Control group
Active

Outcomes
Primary outcome [1] 301628 0
Number of hypoglycaemic events (<4mmol/L). The outcome is assessed via data from the continuous glucose monitoring system.
Timepoint [1] 301628 0
Continuous blood glucose monitoring results after 2 weeks on normal diet, then 2 weeks on IER diet with allocated protocol.
Primary outcome [2] 301661 0
Number of hyperglycaemic events (>10mmol/L). The outcome is assessed via data from the continuous glucose monitoring system.
Timepoint [2] 301661 0
Continuous blood glucose monitoring results after 2 weeks on normal diet, then 2 weeks on IER diet with allocated protocol.
Secondary outcome [1] 333331 0
N/A
Timepoint [1] 333331 0
N/A

Eligibility
Key inclusion criteria
Aged >18yrs
Medication controlled Type 2 Diabetes (sulphonylureas or insulin)
Experiencing hypoglycaemic events during the usual diet
BMI >27kg/m2
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Women who are pregnant or breast feeding or wish to become pregnant.
Weight loss surgery, ongoing weight loss studies or weight loss of 4.5kg or more in past 3mths, IER diet in the last 3mths.
Blood pressure >160/100 mm Hg
Drinking >2 standard drinks per day and unable/unwilling to stop
Eating out more than once a week and not able/willing to decrease for the duration of the study

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)
Following initial contact with the university potential subjects will be screened and randomly allocated one of the arms of the study. Participants will be stratified according to medication type and HbA1c before randomisation. A random number block randomization will be used.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random balanced number sequence generator (randomization.com)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Repeated measures analysis of variance will be use.

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)
SA

Funding & Sponsors
Funding source category [1] 296072 0
University
Name [1] 296072 0
University of South Australia
Address [1] 296072 0
School of Pharmacy and Medical Sciences
GPO Box 2471 Adelaide SA 5000
Country [1] 296072 0
Australia
Primary sponsor type
University
Name
University of South Australia
Address
School of Pharmacy and Medical Sciences
GPO Box 2471 Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 294965 0
None
Name [1] 294965 0
Address [1] 294965 0
Country [1] 294965 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297330 0
University of South Australia's Human Ethics Committee.
Ethics committee address [1] 297330 0
Ethics committee country [1] 297330 0
Date submitted for ethics approval [1] 297330 0
29/03/2017
Approval date [1] 297330 0
10/05/2017
Ethics approval number [1] 297330 0
Ethics committee name [2] 297331 0
University of South Australia
Ethics committee address [2] 297331 0
School of Pharmacy and Medical Sciences
GPO Box 2471 Adelaide SA 5000
Ethics committee country [2] 297331 0
Australia
Date submitted for ethics approval [2] 297331 0
18/01/2017
Approval date [2] 297331 0
Ethics approval number [2] 297331 0

Summary
Brief summary
The purpose of this study is to further our knowledge on how to manage medication changes and to establish a safe and effective medication management plan for people with type 2 diabetes following the 5:2 diet and using medications like sulphonylureas (i.e. Diamicron) and/or insulin.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73726 0
Ms Sharayah Carter
Address 73726 0
Playford Building Office P1-23 City East Campus, Frome Road School of
Pharmacy and Medical Sciences University of South Australia Adelaide SA
5000 Postal address: GPO Box 2471 Adelaide SA 5000
Country 73726 0
Australia
Phone 73726 0
+61 421985405
Fax 73726 0
Email 73726 0
sharayah.carter@mymail.unisa.edu.au
Contact person for public queries
Name 73727 0
Ms Sharayah Carter
Address 73727 0
Playford Building Office P1-23 City East Campus, Frome Road School of
Pharmacy and Medical Sciences University of South Australia Adelaide SA
5000 Postal address: GPO Box 2471 Adelaide SA 5000
Country 73727 0
Australia
Phone 73727 0
+61 421985405
Fax 73727 0
Email 73727 0
sharayah.carter@mymail.unisa.edu.au
Contact person for scientific queries
Name 73728 0
Ms Sharayah Carter
Address 73728 0
Playford Building Office P1-23 City East Campus, Frome Road School of
Pharmacy and Medical Sciences University of South Australia Adelaide SA
5000 Postal address: GPO Box 2471 Adelaide SA 5000
Country 73728 0
Australia
Phone 73728 0
+61 421985405
Fax 73728 0
Email 73728 0
sharayah.carter@mymail.unisa.edu.au

No data has been provided for results reporting
Summary results
Not applicable