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Trial registered on ANZCTR


Registration number
ACTRN12622000889752
Ethics application status
Approved
Date submitted
6/05/2022
Date registered
22/06/2022
Date last updated
22/06/2022
Date data sharing statement initially provided
22/06/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Hybrid Closed Loop in Advanced Renal Disease
Scientific title
Efficacy and Safety of Glucose Control with a Next Generation Hybrid Closed Loop (HCL) System in Adults with Diabetes and Advanced Renal Disease
Secondary ID [1] 307068 0
Nil known
Universal Trial Number (UTN)
U1111-1278-0577
Trial acronym
Renal HCL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 326220 0
Type 1 Diabetes
 326221 0
End stage renal disease 326222 0
CKD IIIB-IV 326223 0
Condition category
Condition code
Metabolic and Endocrine 323524 323524 0 0
Diabetes
Renal and Urogenital 323525 323525 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be educated in carbohydrate counting by a dietitian and receive diabetes education from a diabetes educator via one-on-one consultations up to 2hours per session. Up to 3 sessions per participant for each of diabetes education and carbohydrate counting education will be provided as required.
This education will occur during the 4-6week run-in period prior to randomisation.
Participants will then be randomised to either trial the Medtronic MiniMed 780G hybrid closed loop insulin system or continue their usual care for Stage 1 of the study which will run for a period of 8weeks.

If randomised to the Medtronic MiniMed 780G hybrid closed loop system arm, participants will be given a 2-3hour education session on how to use it.

Whilst using the Medtronic MiniMed 780G system, participants will be wearing continuous glucose monitoring (CGM) which will communicate with the pump to regulate basal insulin delivery via the system's inbuilt algorithm. Participants will still need to input meal-time carbohydrate content into the pump in order to bolus insulin for each meal.

Participants randomised to the usual care arm will continue with their usual insulin delivery mode although doses can be titrated during review visits. Participants in the usual care arm will also wear CGM for the duration of this study stage.

All participants will then crossover to the alternate arm of the study for stage 2 regardless of which arm they were randomised to initially. Stage 2 will also run for 8weeks and the protocol is identical to stage 1. There will be no washout period between treatments.
Intervention code [1] 323522 0
Treatment: Devices
Comparator / control treatment
Participants' usual diabetes management (ie multiple daily injections of insulin or non hybrid closed loop insulin pump therapy), with the addition of real time CGM
Control group
Active

Outcomes
Primary outcome [1] 331278 0
Primary Efficacy Endpoint: Percent time in sensor glucose target range (3.9–10.0 mmol/L) with HCL versus Usual Care + Real Time (RT) CGM as measured by CGM
Timepoint [1] 331278 0
The final 3 weeks of each study stage
Primary outcome [2] 331279 0
Primary Safety Endpoint: Percent time in sensor glucose target range (<3.0 mmol/L) with HCL versus Usual Care + RT CGM, measured by CGM.
Timepoint [2] 331279 0
Final 3 weeks of each study stage
Secondary outcome [1] 409407 0
Glucose control as assessed by standardised CGM metrics:
i. Proportion of time spent 3.9–10.0 mmol/L (excluding the primary outcome)
ii. Proportion of time spent <2.8 mmol/L
iii. Proportion of time spent <3.3 mmol/L
iv. Proportion of time spent <3.9 mmol/L
v. Proportion of time spent 3.9–7.8 mmol/L
vi. Proportion of time spent >10.0 mmol/L
vii. Proportion of time spent >13.9 mmol/L
viii. Proportion of time spent >16.7 mmol/L
ix. Glucose variability: SD and coefficient of variation
x. Mean glucose
Timepoint [1] 409407 0
Final 3 weeks of each study stage
Secondary outcome [2] 409408 0
HbA1c with blood samples
Timepoint [2] 409408 0
At the end of each study stage
Secondary outcome [3] 409409 0
Symptomatic hypoglycaemia as recorded by an event diary
Timepoint [3] 409409 0
Duration of study
Secondary outcome [4] 409410 0
Safety Outcomes:
(a) Episodes of CGM time in <3.0mmol/L range lasting >15minutes.
(b) Hospital presentations for diabetic ketoacidosis or hyperosmolar non-ketotic hyperglycaemia (n)
(c) Hospitalisation and non-hospitalised severe hypoglycaemia (n)
Participants will keep an event diary on a smartphone app for hypoglycaemic events and will also be asked at each review visit about occurrences of severe hypoglycaemia or hospitalisations.
Timepoint [4] 409410 0
Duration of study
Secondary outcome [5] 409411 0
eGFR (Subgroup A only) - on blood sample
Timepoint [5] 409411 0
End of each study stage
Secondary outcome [6] 409412 0
Participant experiences with HCL, assessed via semi-structured interviews
Timepoint [6] 409412 0
End of each study stage
Secondary outcome [7] 409413 0
HCL System Utility
(a) Time spent changing sensor and insulin set as assessed by timer on smartphone app that participant will activate when doing this activity
Timepoint [7] 409413 0
Duration of HCL study arm
Secondary outcome [8] 409414 0
HCL system performance:
(a) Proportion of time Automode is active as assessed by insulin pump uploads
(b) Sensor MARD as assessed by CGM upload and capillary glucose meter uploads.
(c) Sensor failures as assessed by event diary on smartphone app
(d) Insulin set failures as assessed by event diary on smartphone app
Timepoint [8] 409414 0
Duration of HCL study arm
Secondary outcome [9] 409415 0
Exploratory Endpoint:
Changes in novel measures of glycaemia as assessed by blood samples
Timepoint [9] 409415 0
End of each study stage
Secondary outcome [10] 410021 0
K+ pre-dialysis (Subgroup C) - on blood sample
Timepoint [10] 410021 0
At end of each study stage
Secondary outcome [11] 410022 0
Urine albumin/ Cr ratio (Subgroup A only) - on urine sample
Timepoint [11] 410022 0
End of each study stage
Secondary outcome [12] 410023 0
Satisfaction with diabetes treatment: The Diabetes Treatment Satisfaction Questionnaire
Timepoint [12] 410023 0
End of each study stage
Secondary outcome [13] 410024 0
Fear of hypoglycaemia: Hypoglycaemia Fear Survey [HFS-II]
Timepoint [13] 410024 0
End of each study stage
Secondary outcome [14] 410025 0
Hypoglycaemia awareness: Gold Score and Clarke Score
Timepoint [14] 410025 0
End of each study stage
Secondary outcome [15] 410026 0
Diabetes distress: Problem Areas in Diabetes [PAID]
Timepoint [15] 410026 0
End of each study stage
Secondary outcome [16] 410027 0
Diabetes distress: Pittsburgh Sleep Quality Index [PSQI]
Timepoint [16] 410027 0
End of each study stage
Secondary outcome [17] 410028 0
Actigraph Metrics for sleep architecture
Timepoint [17] 410028 0
End of each study stage
Secondary outcome [18] 410029 0
Sleep diary
Timepoint [18] 410029 0
End of each study stage
Secondary outcome [19] 410030 0
Cognitive function: Montreal Cognitive Assessment 
Timepoint [19] 410030 0
End of each study stage

Eligibility
Key inclusion criteria
•Age 18-70 years
•Type 1 Diabetes of at least 1-year duration or insulin requiring Type 2 Diabetes
•Managed with multiple daily insulin injections or insulin pump therapy
•HbA1c <10.5%
•Renal function falls into one of the following 3 groups:
·Group A: Stage 3B and Stage 4 renal failure (eGFR <45 and >15mL/min/1.73m2)
·Group B: ESRD requiring peritoneal dialysis
·Group C: ESRD requiring haemodialysis
•Total daily dose of insulin <200 units
•Participant (and carer where applicable) is fluent in English reading and writing
•Willing to learn how to carbohydrate count and to apply this knowledge
•Have a computer with internet access
•Have access to Smart device with data plan
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
•Already using a hybrid closed loop system
•On sulphonylureas or SGLT2 inhibitors
•For Group A patients – on metformin or GLP1 analogues outside of regulatory guidelines
•For Group B and C patients – on any non-insulin glucose lowering therapies
•History of diabetic ketoacidosis  
•Systemic steroid therapy within past four weeks
•Moderate to severe cognitive impairment precluding the use of insulin pump therapy
•Major allergy to tape or adhesives
•Women who are pregnant or planning pregnancy during the study period
•Major life-threatening illness limiting the participant’s life expectancy to <6 months
•Major psychiatric history
•On peritoneal dialysis using icodextrin

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)
Allocation concealed via sequentially-numbered sealed opaque envelopes until participant enrolment in the study has been completed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a computerised sequence generation,
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Assuming a baseline time in range 55% and a SD of 13.2% to detect an increment of 8% with 90% power , a total of 31 participants are required.  


Data will be analysed for all participants combined on intention to treat basis. Mixed effect linear regression (period adjusted) or period adjusted sign test will be used for analysis of primary and secondary outcomes.

Count outcomes (hypoglycaemia events) will be analysed using mixed effects negative binomial regression with offset being days in the study. Pre-specified subgroup analysis will involve separate analysis for each of the subgroups (A, B and C). 

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/07/2022
Actual
Date of last participant enrolment
Anticipated
1/07/2023
Actual
Date of last data collection
Anticipated
1/11/2023
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,SA,VIC
Recruitment hospital [1] 22322 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 22323 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 22324 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 22326 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 22327 0
The Canberra Hospital - Garran
Recruitment postcode(s) [1] 37488 0
2605 - Garran
Recruitment postcode(s) [2] 37485 0
3050 - Parkville
Recruitment postcode(s) [3] 37483 0
3065 - Fitzroy
Recruitment postcode(s) [4] 37484 0
3084 - Heidelberg
Recruitment postcode(s) [5] 37487 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 311374 0
Other Collaborative groups
Name [1] 311374 0
Australian Centre for Accelerating Diabetes Innovations
Country [1] 311374 0
Australia
Funding source category [2] 311376 0
Charities/Societies/Foundations
Name [2] 311376 0
Diabetes Australia
Country [2] 311376 0
Australia
Funding source category [3] 311377 0
Hospital
Name [3] 311377 0
St Vincent's Hospital Melbourne
Country [3] 311377 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Mebourne
Address
41 Victoria Parade
Fitzroy, 3065
Victoria, Australia
Country
Australia
Secondary sponsor category [1] 312766 0
None
Name [1] 312766 0
Address [1] 312766 0
Country [1] 312766 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310863 0
St Vincent's Hospital Melbourne HREC
Ethics committee address [1] 310863 0
41 Victoria Parade Fitzroy, 3065 Victoria, Australia
Ethics committee country [1] 310863 0
Australia
Date submitted for ethics approval [1] 310863 0
15/02/2022
Approval date [1] 310863 0
30/03/2022
Ethics approval number [1] 310863 0
HREC 031/22

Summary
Brief summary
This proposal consists of a two-stage randomized crossover study comparing automated subcutaneous insulin delivery also known as Hybrid Closed Loop (HCL) therapy with usual care and CGM in people with type 1 and type
2 diabetes complicated by advanced renal disease and managed with insulin. Participants will be recruited from three groups: (A) advanced renal disease not on dialysis; (B) those managed with peritoneal dialysis;
(C) those managed with haemodialysis in ratios of 2:1:1 respectively. All consented participants will enter a 6-week run-in period where baseline demographic data will be collected, diabetes education and carbohydrate count education provided. During the final three weeks of run-in continuous glucose monitoring (CGM) data will be collected following which HbA1c, and questionnaires assessing psychosocial function will be administered. Participants completing run-in-will receive in random order the Medtronic 780G CL system or usual care with CGM. Each of the two stages will last 8 weeks. For the last 3 weeks of each stage CGM data will be collected. Following each stage blood will be collected for electrolytes and an HbA1c, Questionnaires will be administered. Data will be collected post-randomisation in real-time on HCL technical performance and time spent by the participants on changing insulin-sets and glucose sensors.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 119138 0
Prof David O'Neal
Address 119138 0
St Vincent's Hospital Melbourne 41 Victoria Parade Fitzroy 3065 Victoria, Australia
Country 119138 0
Australia
Phone 119138 0
+61 425731665
Fax 119138 0
Email 119138 0
dno@unimelb.edu.au
Contact person for public queries
Name 119139 0
Ms Catriona Sims
Address 119139 0
The University of Melbourne, Department of Medicine 41 Victoria Parade Fitzroy 3065 Victoria, Australia
Country 119139 0
Australia
Phone 119139 0
+61 417482010
Fax 119139 0
Email 119139 0
catriona.sims@unimelb.edu.au
Contact person for scientific queries
Name 119140 0
Prof David O'Neal
Address 119140 0
St Vincent's Hospital Melbourne 41 Victoria Parade Fitzroy 3065 Victoria, Australia
Country 119140 0
Australia
Phone 119140 0
+61 425731665
Fax 119140 0
Email 119140 0
dno@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
individual participant data underlying published results only.
When will data be available (start and end dates)?
immediately following publications, no end date.
Available to whom?
case by case basis at the discretion of the primary sponsor.
Available for what types of analyses?
any purpose
How or where can data be obtained?
access subject to approvals by principal investigator.

email: dno@unimelb.edu.au


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
No additional documents have been identified.