ANZCTR - Registration

Registration number

ACTRN12624000907549

Ethics application status

Approved

Date submitted

11/07/2024

Date registered

25/07/2024

Date last updated

11/05/2025

Date data sharing statement initially provided

25/07/2024

Type of registration

Prospectively registered

Titles & IDs

Public title

Next Generation Automated Insulin Delivery in Children and Adults with Type 1 Diabetes

Scientific title

Effectiveness and safety of a Novel Medtronic Experimental Automated Insulin Delivery (NMX-AID) system in children and adults with type 1 diabetes

Secondary ID [1]

0005-AHCL

Universal Trial Number (UTN)

U1111-1302-6776

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Type 1 diabetes

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This is an up to 82-week multiphase single site and single arm clinical trial with an expected duration of an individual’s study participation of up to 75 weeks. The trial consists of 3 study periods (described below). The co-primary objectives of this exploratory study are to investigate the safety and effectiveness of a Novel Medtronic Experimental Automated Insulin Delivery (NMX-AID) system in children (2 – 17 years, inclusive) and adults (18 years and older) with type 1 diabetes. All study outcomes are exploratory.
Period 1:
For baseline data collection, participants will be trained in the use of MiniMed™ 780G AHCL system with Guardian 4 sensors and Guardian Link 4 transmitters (Medtronic) and wear this system for 3 weeks (NB: All participants in this study will have prior experience using the MiniMed 770G/780G system).
Following the 3-week baseline data collection, participants will undergo NMX-AID system training (approx. 5 hours) and use the system for up to 9 weeks (duration dependent on participant age as described below). Enrollment will be staggered by age groups, with adults (aged 18 years and older) starting first, followed by children aged 7 to 17 and lastly children 2-6 years of age.
- Adults (aged 18 years and older): Following training on the NMX-AID system, adult participants will use the system for 9 weeks at home.
- Children 7 to 17 years of age (inclusive) will commence the study following study completion of adult participants and no detection of safety concerns (severe hypoglycaemia or diabetic ketoacidosis attributable to NMX-AID system wear).
Immediately following training on the NMX-AID system, children aged 7-17 years (together with a parent/guardian) will enter a supervised hotel phase for 5 days/4 nights. Constant on-site supervision will be provided by health care professionals (HCP; medical and nursing staff), including overnight monitoring using CareLink™ Clinical App, which allows for remote data monitoring from a HCP's study smartphone. Following the supervised hotel phase, participants will use the NMX-AID system for 7 weeks at home, with support from their parent/guardian.
- Children 2-6 years of age (inclusive) will commence the study following study completion of children aged 7-17 years when the system is considered ready for progression to this age group. This will be done in Period 3 (below).
Period 2:
After completion of Period 1, participants will enter an up to 35-week Observation Period, where they will transition back to the 780G AHCL system, including the Guardian 4 CGM system, provided through the study. The study team will be available for any questions or concerns by participants and adverse event collection will continue during the Observation Period. During this time, algorithm optimization based on Period 1 outcomes will be performed. Subsequently, use of the updated NMX-AID system will resume (detailed below).
Period 3:
Expected duration of an individual’s study participation during this period is up to 28 weeks. Following an up to 4-week baseline data collection, participants will undergo NMX-AID training (up to 4 hours) and use the system for up to 24 weeks at home. The study design for Period 3 will be similar to the staggered design described above for Period 1: First, adults (18 years and older) will commence. Once all adult participants have completed a minimum of 1 week (no upper limit) of the study and no safety concerns identified, then children aged 7-17 years will commence. Once these participants have completed a minimum of 2 weeks (no upper limit) of the study and no safety concerns identified, then children aged 2-6 years will commence.

The NMX-AID insulin pump is capable of continuous insulin delivery, at set and variable rates, for the management of diabetes mellitus in persons requiring insulin. When used with the continuous glucose monitoring (CGM) components (Simplera Sync), the pump system is capable of continuous or periodic monitoring of glucose levels via a sensor that is inserted in the interstitial fluid under the skin, including the detection of possible low or high blood glucose episodes. The pump also displays glucose values, storing the data so that it can be retrospectively analysed to track patterns and improve diabetes management. The NMX-AID system has the capability to operate in Manual Mode (also referred to as open loop) or in Auto Mode (also referred to as closed loop). While users have the option to manually announce meals to the system, the closed loop algorithm of the NMX-AID system enables the auto-delivery of meal insulin boluses without user input or acknowledgement. When Auto Mode is enabled, the sensor glucose (SG) value received by the pump from the CGM system will be used to automatically calculate the required insulin dose. It will then deliver insulin to the user, at five-minute intervals, to achieve glycaemic control. Basal rates are set for periods of Manual Mode (open loop) therapy. When Auto Mode is not enabled, the user may use the Low Management features. Here, basal rate delivery will be suspended either when the SG has reached a programmed low glucose threshold (Suspend on Low) or before the SG has reached the programmed low glucose threshold (Suspend before Low).
Participants will receive face-to-face education at the study site by trained study staff (research nurses or diabetes educators with diabetes knowledge who are insulin pump trainers) based on the manufacturer's user guides. The initial educational session will take approximately 4-5 hours, including the device set-up of the pump. All participants will be monitored remotely by study staff during at-home NMX-AID system use. Monitoring will occur in form of review of system data uploads via CareLink™ software and phone calls with participants or parents/guardians (as applicable) Participants’ pump data will be automatically uploaded to CareLink™ through the MiniMed™ Mobile phone app, which will be installed on participants’ phones and is connected with the pump via Bluetooth, every 24 hours, where study staff can review the data and give feedback to refine pump settings if necessary. These refinements are personalised based on the participant’s uploaded data and will happen after each review of the uploaded pump data.

Intervention code [1]

Treatment: Devices

Comparator / control treatment

This is a single-arm study.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Glycaemic control as measured by percentage of time in range 3.9 – 10mmol/L.

Timepoint [1]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Primary outcome [2]

Glycaemic control as measured by percentage of time below 3.9 mmol/L.

Timepoint [2]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [1]

Glycaemic control as measured by percentage of time below 3.0 mmol/L.

Timepoint [1]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [2]

Glycaemic control as measured by percentage of time above 10.0 mmol/L.

Timepoint [2]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [3]

Glycaemic control as measured by percentage of time above 13.9 mmol/L.

Timepoint [3]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [4]

Glycaemic control as measured by percentage of time in range 3.9 to 7.8 mmol/L.

Timepoint [4]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [5]

Glycaemic control as measured by glycated hemoglobin (HbA1c) from blood samples.

Timepoint [5]

At baseline; during Period 1 at 9 weeks post-intervention commencement for adult participants (18 years and older) and at 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [6]

The change in fear of hypoglycaemia

Timepoint [6]

At baseline; during Period 1 at 9 weeks post-intervention commencement for adult participants (18 years and older) and at 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [7]

The change in diabetes impact and device satisfaction.

Timepoint [7]

At baseline; during Period 1 at 9 weeks post-intervention commencement for adult participants (18 years and older) and at 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [8]

Glucose levels during the day (0600-2359 hours).

Timepoint [8]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [9]

Glucose levels during the night (0000 to 0559 hours).

Timepoint [9]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [10]

Safety of NXG-AID system

Timepoint [10]

Continuously from start of baseline to end of study at 9 weeks post-intervention commencement in Period 3.

Secondary outcome [11]

Safety of NXG-AID system

Timepoint [11]

Continuously from start of baseline to end of study at 9 weeks post-intervention commencement in Period 3.

Secondary outcome [12]

Platform performance as measured by percentage of time of sensor wear

Timepoint [12]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [13]

Platform performance as measured by percentage of insulin delivery distribution.

Timepoint [13]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [14]

Platform performance as measured by percentage of time spent in automode,

Timepoint [14]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [15]

Platform performance as measured by alarm frequency.

Timepoint [15]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [16]

Platform performance as measured by amount of carbohydrates entered.

Timepoint [16]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [17]

Glycaemic control as measured by coefficient of variation.

Timepoint [17]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [18]

Glycaemic control as measured by sensor glucose concentration.

Timepoint [18]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [19]

Glycaemic control as measured by proportion of participants meeting the glycaemic target of spending equal to or greater than 70% of time in range 3.9 – 10mmol/L.

Timepoint [19]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [20]

Glycaemic control as measured by proportion of participants meeting the glycaemic target of having a glycated hemoglobin (HbA1c) result of less than 53mmol/mol.

Timepoint [20]

At baseline; during Period 1 at 9 weeks post-intervention commencement for adult participants (18 years and older) and at 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 9 weeks post-intervention commencement for all participants (2 years and older).

Secondary outcome [21]

Glycaemic control as measured by proportion of participants meeting the glycaemic target of spending less than 4% of time below 3.9mmol/L.

Timepoint [21]

At baseline; during Period 1 at 3, 6, and 9 weeks post-intervention commencement for adult participants (18 years and older) and at 3, 5, and 7 weeks post-intervention commencement in child participants (7-17 years); and during Period 3 at 3, 6, and 9 weeks post-intervention commencement for all participants (2 years and older).

Eligibility

Key inclusion criteria

1. Male or female aged 2 years or older on day of consent.
2. Type 1 diabetes as per the American Diabetes Association Classification.
3. Duration of diabetes at least 12 months prior to Study Day 1 (or 6 months for those <7 years).
4. HbA1c of equal to or greater than 6.5% (48 mmol/mol) on day of consent.
5. Previous experience with 770G/780G systems for at least 3 months prior to study start.
6. Minimum daily insulin requirement (Total Daily Dose) of greater than or equal to 6 units/day.
7. Willing and able to adhere to the study protocol.
8. Adults aged 18 years or older with access to the internet and a computer system that meets requirements for uploading the study pump (willingness to attend clinic for upload is possible if no other option).
9. Children aged 2-17 years (inclusive) with at least one parent/legal guardian willing and able to upload system data as per preceding criterion, and proficient in basic diabetes management.

Minimum age

2 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

1. Previous significant adverse event at investigator discretion that precludes the participant safely using advanced diabetes technology/sensors e.g., unable to wear glucose sensors due to prior cutaneous adverse events.
2. Use of systemic glucocorticoids within 2 weeks prior to the Baseline visit.
3. Current use of Metformin, SGLT-2 or GLP-1 medications.
4. History or current evidence of severe psychiatric disorder, uncontrolled seizure disorder, renal impairment or cardiovascular disease (including uncontrolled hypertension), or severe visual impairment that in the opinion of the Investigator would limit study involvement or be a safety issue.
5. Moderate to severe diabetic retinopathy.
6. If participant is of child-bearing potential, is pregnant or becomes pregnant while participating in the study. A positive urine pregnancy test at Screening is exclusionary.
7. Any clinically significant pre-existing medical condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
8. Planned travel either outside New Zealand, or in remote areas within New Zealand that would hinder study system data uploads.

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

26/08/2024

Actual

21/08/2024

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

30

Accrual to date

25

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Medtronic Inc.

Country [1]

United States of America

Primary sponsor type

Government body

Name

Health New Zealand - Southern

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern B Health and Disability Ethics Committee

Ethics committee address [1]

https://ethics.health.govt.nz/about/northern-b-health-and-disability-ethics-committee/

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

12/01/2024

Approval date [1]

23/02/2024

Ethics approval number [1]

2024 FULL 19434

Summary

Brief summary

Despite modern treatment, complications of type 1 diabetes (T1D) and high disease burden continue to be a reality for patients. While automated insulin delivery (AID) systems have been demonstrated to improve health outcomes, high burden of care still remains for some using these systems. This study investigates the ability of a new next-generation AID (NMX-AID) system to improve glucose levels and reduce disease burden in children and adults with T1D. The NMX-AID system under investigation has the ability to auto-deliver meal insulin boluses without user input or acknowledgement. The study will enrol 30 participants aged 2 years and older. Following 3 weeks of baseline assessments, participants will use of the NMX-AID system for up to 9 weeks (duration dependent on participant age) at home. This will be followed by an up to 35-week observation period, where participants will switch back to the 780G system and during which algorithm optimization will occur. Subsequently, participants will use the updated NMX-AID system for up to a further 24 weeks at home.

Trial website

Public notes

Contacts

Principal investigator

Name

Prof Benjamin J Wheeler

Address

Department of Women's and Children's Health Otago Medical School - Dunedin Campus PO Box 56 Dunedin 9054 New Zealand

Country

New Zealand

Phone

+64 274701980

Email

[email protected]

Contact person for public queries

Name

Benjamin J Wheeler

Address

Department of Women's and Children's Health Otago Medical School - Dunedin Campus PO Box 56 Dunedin 9054 New Zealand

Country

New Zealand

Phone

+64 274701980

Email

[email protected]

Contact person for scientific queries

Name

Benjamin J Wheeler

Address

Department of Women's and Children's Health Otago Medical School - Dunedin Campus PO Box 56 Dunedin 9054 New Zealand

Country

New Zealand

Phone

+64 274701980

Email

[email protected]

Trial Review

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Documents added automatically