The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000515190
Ethics application status
Approved
Date submitted
20/03/2019
Date registered
1/04/2019
Date last updated
2/02/2021
Date data sharing statement initially provided
1/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Older Adult Closed Loop (ORACL) Study for Type 1 Diabetes
Scientific title
Older Adult Closed Loop (ORACL) Study for Glucose Management in Type 1 Diabetes
Secondary ID [1] 297658 0
None
Universal Trial Number (UTN)
U1111-1229-7168
Trial acronym
ORACL
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
type 1 diabetes 311935 0
Condition category
Condition code
Metabolic and Endocrine 310518 310518 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This randomised crossover study compares closed-loop (CL) therapy versus open-loop (OL) therapy (with insulin pump and real-time continuous glucose monitoring (CGM)) for older adults with type 1 diabetes.

This study will consist of 12 visits over approximately 9-11 months. Duration of visits will be up to 6 hours to provide participant education and collect study outcome data. All procedures involving study participants will be undertaken by study doctors, research nurses, dietitians and psychologists. Participants will be provided with study devices and will receive face-to-face education regarding their use. Clinician researchers will determine when educational requirements have been completed. The study intervention is an insulin delivery system, that has CL capability to continuously deliver automated subcutaneous insulin doses via a cannula placed transcutaneously. The CL system comprises a CGM device (with transcutaneous glucose sensor filament connected to an external recorder), coupled with an insulin pump containing a computerised automated insulin delivery algorithm. Glucose sensor information is transmitted to the insulin pump, and the dose of insulin is calculated by the algorithm and automatically delivered every 5 minutes to account for basal insulin requirements. User-initiated bolus insulin doses are required for meals. Intervention adherence and function will be assessed via pump upload.

The study involves a run-in period for education and collection of pre-randomisation data (up to 10 weeks depending on individual participant educational requirements), pre-randomisation measures (2 weeks), randomisation, followed by two 4-month study stages undertaken in random order. The stages are (i) CL with automated basal insulin delivery, and (ii) OL with manual insulin delivery via pump and real-time CGM. There will no wash-out period between stages.
Intervention code [1] 313891 0
Treatment: Devices
Comparator / control treatment
OL stage - CGM plus manual determination of subcutaneous insulin doses continuously delivered via insulin pump as per the individual's usual clinical care.
Control group
Active

Outcomes
Primary outcome [1] 319375 0
Proportion of time spent with sensor glucose 3.9–10.0 mmol/L
Timepoint [1] 319375 0
Final 3 months of each study stage
Secondary outcome [1] 367930 0
Proportion of time spent with sensor glucose 3.9–10.0 mmol/L
Timepoint [1] 367930 0
Final 3 months of each study stage for:
1) day [06:00-23:59]
2) night [00:00-05:59]
Secondary outcome [2] 367931 0
Proportion of time spent with sensor glucose <3.0 mmol/L
Timepoint [2] 367931 0
Final 3 months of each study stage for:
1) 24 h/day
2) day [06:00-23:59]
3) night [00:00-05:59]
Secondary outcome [3] 367932 0
Proportion of time spent with sensor glucose <3.3 mmol/L
Timepoint [3] 367932 0
Final 3 months of each study stage for:
1) 24 h/day
2) day [06:00-23:59]
3) night [00:00-05:59]
Secondary outcome [4] 367933 0
Proportion of time spent with sensor glucose <3.9 mmol/L
Timepoint [4] 367933 0
Final 3 months of each study stage for:
1) 24 h/day
2) day [06:00-23:59]
3) night [00:00-05:59]
Secondary outcome [5] 367934 0
Proportion of time spent with sensor glucose 3.9–7.8 mmol/L
Timepoint [5] 367934 0
Final 3 months of each study stage for:
1) 24 h/day
2) day [06:00-23:59]
3) night [00:00-05:59]
Secondary outcome [6] 367935 0
Proportion of time spent with sensor glucose >10.0 mmol/L
Timepoint [6] 367935 0
Final 3 months of each study stage for:
1) 24 h/day
2) day [06:00-23:59]
3) night [00:00-05:59]
Secondary outcome [7] 367936 0
Proportion of time spent with sensor glucose >13.9 mmol/L
Timepoint [7] 367936 0
Final 3 months of each study stage for:
1) 24 h/day
2) day [06:00-23:59]
3) night [00:00-05:59]
Secondary outcome [8] 367937 0
Proportion of time spent with sensor glucose >16.7 mmol/L
Timepoint [8] 367937 0
Final 3 months of each study stage for:
1) 24 h/day
2) day [06:00-23:59]
3) night [00:00-05:59]
Secondary outcome [9] 367938 0
Mean CGM glucose
Timepoint [9] 367938 0
Final 3 months of each study stage for:
1) 24 h/day
2) day [06:00-23:59]
3) night [00:00-05:59]
Secondary outcome [10] 367939 0
CGM glucose variability (standard deviation, coefficient of variation)
Timepoint [10] 367939 0
Final 3 months of each study stage for:
1) 24 h/day
2) day [06:00-23:59]
3) night [00:00-05:59]
Secondary outcome [11] 367940 0
HbA1c (samples tested at a centralised DCCT-aligned laboratory).
Timepoint [11] 367940 0
1) End of Study Stage 1
2) End of Study Stage 2
Secondary outcome [12] 367941 0
Functional ability assessed by Katz ADLs and Lawton-Brody Instrumental ADLs questionnaires
Timepoint [12] 367941 0
1) End of Study Stage 1
2) End of Study Stage 2
Secondary outcome [13] 367942 0
Frailty assessed by physical testing and FRAIL, MNA and Sarcopenia SARC-F questionnaires
Timepoint [13] 367942 0
1) End of Study Stage 1
2) End of Study Stage 2
Secondary outcome [14] 367943 0
Diabetes-related ambulance attendances (by study-specific questionnaire)
Timepoint [14] 367943 0
From randomisation to end of Study Stage 2
Secondary outcome [15] 367944 0
Diabetes-related hospitalisations (by study-specific questionnaire then verified via hospital records)
Timepoint [15] 367944 0
From randomisation to end of Study Stage 2
Secondary outcome [16] 367945 0
Incident falls (by study-specific questionnaire)
Timepoint [16] 367945 0
From randomisation to end of Study Stage 2
Secondary outcome [17] 367946 0
Incident delirium (by study-specific questionnaire then verified via medical records)
Timepoint [17] 367946 0
From randomisation to end of Study Stage 2
Secondary outcome [18] 367947 0
Incident pressure sores (by study-specific questionnaire)
Timepoint [18] 367947 0
From randomisation to end of Study Stage 2
Secondary outcome [19] 367948 0
Incident infections (by study-specific questionnaire)
Timepoint [19] 367948 0
From randomisation to end of Study Stage 2
Secondary outcome [20] 367949 0
Episodes of severe hypoglycaemia (by study-specific questionnaire)
Timepoint [20] 367949 0
From randomisation to end of Study Stage 2
Secondary outcome [21] 367950 0
Episodes of diabetic ketoacidosis (by study-specific questionnaire then verified by medical records)
Timepoint [21] 367950 0
From randomisation to end of Study Stage 2
Secondary outcome [22] 367951 0
Total daily dose of insulin (from insulin pump data)
Timepoint [22] 367951 0
Final 3 months of each study stage
Secondary outcome [23] 367952 0
Cognitive functioning via MOCA, MMSE, NART, Trails Making Tasks B, SDMT and Grooved Pegboard
Timepoint [23] 367952 0
1) End of Study Stage 1
2) End of Study Stage 2
Secondary outcome [24] 367953 0
Psychosocial well-being via INSPIRE, HFS-II, Gold and Clarke scores, PAID-5, GDS, DIDP and semi-structured interviews
Timepoint [24] 367953 0
1) End of Study Stage 1
2) End of Study Stage 2
Secondary outcome [25] 367954 0
CGM glucose patterns while driving (using a vehicle driving logger device)
Timepoint [25] 367954 0
Final 3 months of each study stage
Secondary outcome [26] 367955 0
Sleep quality via PSQI and actigraphy data
Timepoint [26] 367955 0
1) End of Study Stage 1
2) End of Study Stage 2
Secondary outcome [27] 367956 0
Electrocardiograph (ECG) profile
Timepoint [27] 367956 0
1) End of Study Stage 1
2) End of Study Stage 2

Eligibility
Key inclusion criteria
1) Type 1 diabetes of >=10 years duration
2) Using insulin pump therapy (>=1 year pump experience) with established pump settings
3) HbA1c <=10.5%
4) Able to use study devices (with or without caregiver assistance)
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Non-type 1 diabetes
2) Use of closed-loop insulin delivery within past 3 months
3) Nephropathy with eGFR <30 mL/min/1.73m^2 or on dialysis
4) Use of any glucose-lowering agent other than insulin within past 3 months
5) Corticosteroid medication within past 3 months (or anticipated during the study period)
6) Inability to tolerate skin adhesives
7) History of myocardial infarction, severe uncontrolled heart failure, unstable angina, transient ischaemic attack, stroke, or thromboembolic disease in past 3 months
8) Clinical diagnosis of moderate or severe dementia

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)
Randomisation will be delivered via computer program. This information will not be available to research site personnel or participants until time of randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will occur using a central computer. The order of study stages will be randomly assigned, stratified according to study site, using block randomisation with random permuted blocks.
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/efficacy
Statistical methods / analysis
Analyses will be on an intention-to-treat basis. We will test for period and carry-over effects. Should no bias from period and carry-over effects be statistically significant, paired t-tests will be used to assess the significance of time-in-target range between CL versus OL. However, should there be period and/or carry-over effects, mixed effects modelling will be employed. No adjustment for multiplicity is planned. No interim analysis is planned.

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)
VIC
Recruitment hospital [1] 13330 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 13331 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 25931 0
3065 - Fitzroy
Recruitment postcode(s) [2] 25932 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 302189 0
Charities/Societies/Foundations
Name [1] 302189 0
JDRF
Country [1] 302189 0
United States of America
Funding source category [2] 302292 0
Charities/Societies/Foundations
Name [2] 302292 0
Diabetes Australia
Country [2] 302292 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Melbourne
Address
27 Victoria Pde
Fitzroy, VIC 3065
Country
Australia
Secondary sponsor category [1] 302033 0
None
Name [1] 302033 0
Address [1] 302033 0
Country [1] 302033 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302869 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 302869 0
Ethics committee country [1] 302869 0
Australia
Date submitted for ethics approval [1] 302869 0
17/12/2018
Approval date [1] 302869 0
04/03/2019
Ethics approval number [1] 302869 0
HREC 275/18

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

Contacts
Principal investigator
Name 91670 0
Dr Sybil McAuley
Address 91670 0
Department of Medicine
University of Melbourne, St Vincent's Hospital Melbourne
29 Regent St Fitzroy
Melbourne, Victoria 3065
Country 91670 0
Australia
Phone 91670 0
+61 3 9231 2211
Fax 91670 0
Email 91670 0
Contact person for public queries
Name 91671 0
Charlotte Grills
Address 91671 0
Department of Medicine
University of Melbourne, St Vincent's Hospital Melbourne
29 Regent St Fitzroy
Melbourne, Victoria 3065
Country 91671 0
Australia
Phone 91671 0
+61 3 9231 3648
Fax 91671 0
Email 91671 0
Contact person for scientific queries
Name 91672 0
Sybil McAuley
Address 91672 0
Department of Medicine
University of Melbourne, St Vincent's Hospital Melbourne
29 Regent St Fitzroy
Melbourne, Victoria 3065
Country 91672 0
Australia
Phone 91672 0
+61 3 9231 2211
Fax 91672 0
Email 91672 0

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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10412Statistical analysis plan    377153-(Uploaded-11-12-2020-08-26-10)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseClosed-Loop Insulin Delivery Effects on Glycemia during Sleep and Sleep Quality in Older Adults with Type 1 Diabetes: Results from the ORACL Trial.2022https://dx.doi.org/10.1089/dia.2022.0110
EmbaseClosed-Loop Insulin Delivery Versus Sensor-Augmented Pump Therapy in Older Adults With Type 1 Diabetes (ORACL): A Randomized, Crossover Trial.2022https://dx.doi.org/10.2337/dc21-1667
EmbaseGlucose profiles of older adults with type 1 diabetes using sensor-augmented pump therapy in Australia: pre-randomisation results from the ORACL study.2022https://dx.doi.org/10.1016/S2666-7568%2822%2900266-5
EmbaseLived experience of older adults with type 1 diabetes using closed-loop automated insulin delivery in a randomised trial.2023https://dx.doi.org/10.1111/dme.15020
N.B. These documents automatically identified may not have been verified by the study sponsor.