Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000575538
Ethics application status
Approved
Date submitted
10/04/2024
Date registered
7/05/2024
Date last updated
7/05/2024
Date data sharing statement initially provided
7/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and efficacy of the Android Artificial System (AAPS) with advanced bolus-free features in Adults with Type 1 diabetes with extended use.(Close It Extended)
Scientific title
Safety and efficacy of the Android Artificial Pancreas System (AAPS) with advanced bolus-free features in adults with type 1 diabetes with extended use
Secondary ID [1] 311666 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record
This study is a follow up study to ACTRN12622001401741.
The participants who were involved in the study will be offered to continue using AAPS in this study for a period of 12 months. The 38 participants that took part in that study will be the only participants eligible to take part in this study.

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes Mellitus 333123 0
Condition category
Condition code
Metabolic and Endocrine 329817 329817 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The CLOSE IT randomised controlled trial demonstrated the benefits of using AAPS as a fully closed loop system compared to a hybrid closed loop system over 12 weeks. However, the short study duration limits generalizability to real-world long-term use.
There is a need for longer-term evaluation to determine if the benefits of fully closed-loop delivery with AAPS are sustained with prolonged everyday use over 12 months.
Understanding long-term patient experiences and perspectives will help guide education and optimisation of closed-loop systems.
To determine if the efficacy of AAPS used as a fully automated closed-loop system is sustained over 12 months of real-world use in adults with type 1 diabetes.
To assess the impact of prolonged fully closed loop use on glycaemic control, hypoglycaemia, hyperglycaemia, glucose variability, treatment satisfaction, quality of life, and adverse events.
Intervention: Android Artificial Pancreas System (AAPS)
AndroidAPS consists of three main components which all participants will have been using in the 12 weeks prior to this extension study
1. Dexcom G6® CGM: includes a glucose sensor and transmitter attached to the user with the ability to measure interstitial fluid glucose continuously. The CGM data are transferred via Bluetooth to the Dexcom G6® mobile App (an application on the study Android phone). The App can display real-time glucose data.
2. Upgraded YpsoPump®: An upgraded version of YpsoPump® with bidirectional communication capability will be developed for this study to enable communication with the AndroidAPS interface. The YpsoPump has been approved and is currently being used in Australia. (Participants are currently using these pumps in the original study)
3. Lotus: an application on the study Android phone that contains the controller algorithm. It receives real-time CGM data from the Dexcom G6® mobile App and controls the basal insulin delivery by sending commands to YpsoPump®. The basal insulin delivery rate is adjusted every 5 minutes based on varying glucose levels.
This 12-month observational extension of CLOSE IT will enroll all willing participants from the original RCT to continue using AAPS as FCL with remote optimisation and comprehensive outcome assessment. Participants will use the rapid-acting analogue insulin NovoRapid®, or ultra-fast acting insulin Fiasp® throughout the duration of this trial. The primary objective is to evaluate time in range over 12 months. Secondary aims include assessing glycaemic variability, hypoglycaemia, hyperglycaemia, HbA1c, treatment satisfaction, quality of life, system performance metrics, adverse events, and perspectives from questionnaires.

Overall, findings from this 12-month observational extension will determine if the feasibility and efficacy of AAPS as FCL is sustained with prolonged use and provide essential patient-centered insights to inform the development and implementation of fully automated closed-loop systems in real-world clinical care.
The intervention is that all participants will be in Fully Closed Loop (FCL) mode and able to use Novorapid or Fiasp in their Ypsomed pump. The previous study had one arm in Hybrid Closed Loop (announcing meal boluses) and another arm in FCL. (not announcing meal boluses).
Participants have to use AndrioidAPS, 24 hours per day, for a 12 month period
Participants will be using the modified Ypsomed pump given to them in the previous study ACTRn12622001401741 and the same Android study phone.
The amount of insulin administered daily, is determined by the Algorithm in the Lotus App. This takes into account Participants Basal rates over 24 hours, Insulin sensitivity, active insulin time and target BGL., Carbohydrate ratio which were originally worked out by the Diabetes Educator in previous study. They can be adjusted by physicians. The algorithm makes decisions every 5 minutes to deliver very small micro boluses to keep participants close to their target Blood Glucose Level (BGL). It will also stop delivering if the BGL is too low and resume again when BGL is in the normal range 3.9mmol/L-10mmol/L.
All participants have a Night Scout site which all data is uploaded to in real time from the participants use of this system. The study staff can look at these sites at any time and they can access reports from here. The sites are de identified with participants study numbers and unique passwords.
There will be 5 visits - one at the start of the study and one at the end of each 3-month period over the 12 months participants are involved.
At each visit participants will have 5 mls of blood drawn for HBA1C levels, weight measurement, questionnaires to complete, and review of night scout reports (from AAPS) with study physician.
To monitor or assess adherence to the intervention Study staff will send reminders via phone calls, text messages, or emails to prompt participants to adhere to the intervention protocol. visits.
Intervention code [1] 328129 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 337592 0
- Percentage of CGM time in target range (3.9-10.0 mmol/L) with AndroidAPS .
Timepoint [1] 337592 0
Calculated for each 24 hour period during the last two weeks before the 3, 6, 9 and 12 month visits.
Expressed as % of readings in target range out of total readings
Primary outcome [2] 338030 0
Safety outcomes including All adverse events (AEs), adverse device effects (ADE), serious adverse events (SAE), serious adverse device effects (SADE) and device deficiencies (DD) will be documented in a timely manner and reported to the principal investigator throughout the duration of the trial. SAE, SADE, and DD will be reported to the principal investigator within 24 hours. Initial reports will be followed by a detailed report outlining the nature of the event. Participant will notify the study team via phone or email or at Study visits and the study team will record the event on specific form (AE, SAE, SADE, DD form).
Start and stop date of the event;
• A description of the event including any associated symptoms;
• Assessment of seriousness;
• Assessment of intensity;
• Assessment of relationship to the investigational device;
• Intervention/ troubleshooting;
• Outcome.
Severe Hypoglycaemia: Is an event requiring assistance of another person due to altered consciousness to actively administer carbohydrate, glucagon, or other resuscitative actions.

Severe Hyperglycaemia: Is defined as hyperglycaemia (blood glucose greater than (greater than) 16.7 mol/L) with blood glucose ketones greater than (greater than) 1.5 mmol/L, urine ketones moderate or large, or accompanied by symptoms of nausea, vomiting or abdominal pain.

Hyperglycemic events are classified as Diabetic Ketoacidosis (DKA) if the following are present:
• Symptoms such as polyuria, polydipsia, nausea, or vomiting;
• Serum ketones greater than 1.5 mmol/L or large/moderate urine ketones;
• Either arterial blood pH less than 7.30 or venous pH less than 7.24 or serum bicarbonate less than 15; and treatment provided in a Healthcare facility

A Serious Adverse Event (SAE) is an adverse event that:
• Results in death, or
• Is a life-threatening illness or injury, or
• Causes permanent impairment of a body structure or a body function, or
• Requires in-patient or prolonged hospitalisation, or
• Requires medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function.

An ADE is an adverse event related to the use of the investigational medical device. This definition includes adverse events resulting from insufficient or inadequate instructions for use, deployment, implantation, installation, or operation, or any malfunction of the investigational medical device. This also includes any event resulting from use error from intentional misuse of the investigational medical device.

A DD is any inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety, or performance and shall be documented throughout the clinical investigation. NOTE: DD include malfunctions, use errors, and inadequate labelling. However, in clinical management of T1D use errors will not be recorded unless they result in an ADE, because absolute perfect use of the device is not possible in day to day life.
Timepoint [2] 338030 0
All Safety outcomes over the 12 months study for each participant.
Secondary outcome [1] 433818 0
Mean Sensor Glucose value with Android APS
Timepoint [1] 433818 0
- Calculated from CGM data for each 24 hour period during the last two weeks before the 3, 6, 9 and 12 month visits.
Secondary outcome [2] 433819 0
- % CGM time in hypoglycaemia range (less than or equal to 3.9 mmol/L) with AndroidAPS
Timepoint [2] 433819 0
Calculated from CGM data for each 24 hour period during the last two weeks before the 3, 6, 9 and 12 month visits.
Secondary outcome [3] 433820 0
- % CGM time in clinically significant hypoglycaemia range (less than 3.0 mmol/L) with AndroidAPS
Timepoint [3] 433820 0
- Calculated from CGM data for each 24 hour period during the last two weeks before the 3, 6, 9 and 12 month visits.
Secondary outcome [4] 433821 0
- % CGM time in hyperglycaemia range (greater than 10.0 mmol/L) with AndroidAPS.
Timepoint [4] 433821 0
- Calculated from CGM data for each 24 hour period during the last two weeks before the 3, 6, 9 and 12 month visits.
Secondary outcome [5] 433822 0
- % CGM time in significant hyperglycaemic range (greater than 15 mmol/L) with AndroidAPS
Timepoint [5] 433822 0
- Calculated from CGM data for each 24 hour period during the last two weeks before the 3, 6, 9 and 12 month visits
Secondary outcome [6] 433823 0
- Number of symptomatic episodes of hypoglycaemia with AndroidAPS
Timepoint [6] 433823 0
At any time during the 12-month study period that symptomatic and severe episodes based on capillary glucose less than 3.0 mmol/L and /or need for 3rd party assistance occur.
Secondary outcome [7] 433824 0
- Time in fully closed loop
Timepoint [7] 433824 0

Calculated from CGM data for each 24 hour period during the last two weeks before the 3, 6, 9 and 12 month visits
Secondary outcome [8] 433825 0
- Number of hospitalisations for diabetic ketoacidosis with AndroidAPS
Timepoint [8] 433825 0
the number of Adverse events the participants may experience over 12 months of the study period.
Secondary outcome [9] 433826 0
- Parameters of Glycaemic variability based on the conventional deviation of the mean (SD) and coefficient of variation (CV) with AndroidAPS
Timepoint [9] 433826 0
Calculated from CGM data for each 24 hour period during the last two weeks before the 3, 6, 9 and 12 month visits
Secondary outcome [10] 433836 0
- Total daily dose of insulin with AndroidAPS
Timepoint [10] 433836 0
Calculated from CGM data for each 24 hour period during the last two weeks before the 3, 6, 9 and 12 month visits
Secondary outcome [11] 433837 0
Change in body weight
Timepoint [11] 433837 0
Measured at study start and after each 3 month period over 12 months
Secondary outcome [12] 433838 0
EuroQol EQ-5D-5L questionnaire- is a standardized instrument for measuring health-related quality of life (HRQoL).
Timepoint [12] 433838 0
EuroQoL EQ-5D-5L questionnaire at the beginning of study and at the 3, 6, 9 and 12 month visit over the 12 month study
Secondary outcome [13] 434175 0
INSPIRE questionnaires -are about using an automated insulin dosing system (abbreviated AID), sometimes called a closed loop system, artificial pancreas or bionic pancreas. This questionnaire is about living with diabetes and the aspects that may be better or worse by using AID
Timepoint [13] 434175 0
INSPIRE questionnaires (pre-post) Pre at first visit, post at 3, 6, 9, and end of 12 months study visits.
Secondary outcome [14] 434177 0
System Usability Scores (SUS) questionnaires are used to measure how user friendly the Android Artificial System is for the participant.
Timepoint [14] 434177 0
System Usability Score will be completed by participants at the 12-month study visit.

Eligibility
Key inclusion criteria
• Type 1 diabetes > 6 months duration
• Adults aged 18-70 years
• Completion of the CLOSE IT trial (ACTRN12622001401741) and willingness for ongoing use of a FCL system
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Pregnancy or planning a pregnancy in the next 12 months
• Chronic kidney disease (eGFR<45ml/min/1.73m2)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/05/2024
Actual
Date of last participant enrolment
Anticipated
31/01/2025
Actual
Date of last data collection
Anticipated
31/01/2026
Actual
Sample size
Target
38
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26387 0
Baker Heart and Diabetes Institute - Melbourne
Recruitment postcode(s) [1] 42362 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 315993 0
Other
Name [1] 315993 0
Baker Heart abd Diabetes Institute
Country [1] 315993 0
Australia
Primary sponsor type
Other
Name
Baker Heart and Diabetes Institute
Address
Country
Australia
Secondary sponsor category [1] 318464 0
None
Name [1] 318464 0
Address [1] 318464 0
Country [1] 318464 0
Other collaborator category [1] 283003 0
Commercial sector/Industry
Name [1] 283003 0
Ypsomed AG
Address [1] 283003 0
Country [1] 283003 0
Switzerland

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314818 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 314818 0
https://www.alfredhealth.org.au/research/ethics-research-governance
Ethics committee country [1] 314818 0
Australia
Date submitted for ethics approval [1] 314818 0
01/02/2024
Approval date [1] 314818 0
09/04/2024
Ethics approval number [1] 314818 0

Summary
Brief summary
This study aims to assess the safety and efficacy of an Advanced closed-loop Android Artificial Pancreas System over an extended period of 12 months. All participants will continue with the equipment provided for the original study i.e. AAPS using a Ypsomed pump, Dexcom G6 CGM and an Android phone with an installed AAPS algorithm on the Lotus app. The advanced features and enhancements of the algorithm will be activated for all participants at the beginning of this extension trial. Those assigned to Advanced AAPS with announced meals in CLOSE IT will commence using the fully closed loop with no meal announcements. During this study, participants will have the choice of using either NovoRapid® or Fiasp® insulins. Participants will receive support from your usual clinical team in addition to our clinical research team as required. Assessments of HBA1C, weight and questionnaires will be completed at the start and after each 3-month period of the study.This trial is an extension of the original Close It trial ( ACTRN12622001401741).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132822 0
A/Prof Neale Cohen
Address 132822 0
Baker Heart and Diabetes Institute Level 4, 99 Commercial Road Melbourne.3004. Victoria.
Country 132822 0
Australia
Phone 132822 0
+61385321816
Fax 132822 0
Email 132822 0
neale.cohen@baker.edu.au
Contact person for public queries
Name 132823 0
Neale Cohen
Address 132823 0
Baker Heart and Diabetes Institute Level 4, 99 Commercial Road Melbourne.3004. Victoria.
Country 132823 0
Australia
Phone 132823 0
+61385321800
Fax 132823 0
Email 132823 0
neale.cohen@baker.edu.au
Contact person for scientific queries
Name 132824 0
Neale Cohen
Address 132824 0
Baker Heart and Diabetes Institute Level 4, 99 Commercial Road Melbourne.3004. Victoria.
Country 132824 0
Australia
Phone 132824 0
+61385321800
Fax 132824 0
Email 132824 0
neale.cohen@baker.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy laws in Australia


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
22154Ethical approval    387441-(Uploaded-10-04-2024-13-33-48)-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
No additional documents have been identified.