None listed
Conditions
Brief summary
Long-term health complications and increased mortality due to suboptimal glycaemic control are great concerns for patients with type 1 diabetes (T1D). Unfortunately, less than a third of patients meet glycaemic control targets recommended to prevent long-term complications. Evidence suggests that automation of insulin delivery through advanced hybrid closed loop (AHCL) systems may lead to improved health outcomes. This 3-month randomised controlled trial, followed by a 9-month period where control subjects cross over to the intervention arm, will explore the ability of the AHCL system to improve glucose levels and reduce disease burden in children and youth struggling with the maintenance of healthy diabetes control. This study will enrol 80 participants aged 7–25 years at 5 study sites in Aotearoa New Zealand. Baseline data will be collected from eligible subjects. After baseline assessments, subjects will be randomised and either commence use of the AHCL system (intervention arm), or continue their usual diabetes care (control arm) for 3 months. Subsequently, those in the control arm commence use of the AHCL system, and all participants use the system during the 9-month extension phase. The study will conclude after approximately 13 months.
Interventions
This is a 3-month randomized controlled trial (RCT) followed by a 9-month extension phase investigating advanced hybrid closed loop (AHCL) in children and youth with type 1 diabetes (T1D) and high-risk glycaemic control that have previously not been using closed loop therapy. Following baseline assessments of blinded continuous glucose monitoring (CGM) for 21 days (using Guardian 3 sensor and transmitter CGM system), participants will be randomized to AHCL use (intervention group) or their usual
This is a 3-month randomized controlled trial (RCT) followed by a 9-month extension phase investigating advanced hybrid closed loop (AHCL) in children and youth with type 1 diabetes (T1D) and high-risk glycaemic control that have previously not been using closed loop therapy. Following baseline assessments of blinded continuous glucose monitoring (CGM) for 21 days (using Guardian 3 sensor and transmitter CGM system), participants will be randomized to AHCL use (intervention group) or their usual diabetes management care (control group). The intervention group will undergo a run-in period of 72 hours running as sensor augmented pump (SAP) with predictive low glucose monitoring (PLGM) to allow subjects to familiarize with the system and for control to be optimized, and will then enter into a 3-month study period of using the insulin pump in its trial settings in Auto mode. All participants will use the AHCL system in Auto mode for a further 9 months during the extension phase. While participants have the option to enable/disable Auto mode during the RCT and extension phase, the AHCL system provides optimal results in Auto mode and therefore participants are encouraged to keep the system in Auto mode during the study. Expected duration of subject participation is 13 months (21 days baseline assessments, 3 days run-in, 3 months RCT, 9 months extension). The study intervention is the Medtronic MiniMed™ 780G AHCL insulin pump running in AHCL mode. In use with the continuous glucose monitoring (CGM) components (Guardian 4 Sensor and Guardian 4 transmitter, and Medtronic's newest Synergy CGM system), the MiniMed™ 780G AHCL pump is capable of continuous insulin delivery at set and variable rates, and the 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 this data so that it can be retrospectively analysed. The MiniMed™ AHCL insulin pump also includes the closed loop algorithm as part of the SmartGuard™ collection of features. SmartGuard™ is comprised of Manual Mode Low Management, which includes the Suspend On Low feature (suspends insulin delivery when a pre-set low sensor glucose [SG] threshold is reached), the Suspend Before Low feature (enables insulin to suspend 30 minutes before a pre-set low SG threshold is reached) and Auto Mode (hybrid closed loop) feature. The pump can also be used as a simple pump without CGM or as a SAP without use of the SmartGuard™ features. When Auto Mode is enabled, the sensor glucose values (SGVs) 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 patient, at five-minute intervals, to achieve glycaemic control. With the AHCL system, subjects must still deliver bolus insulin for meals. In addition, the setting for active insulin must be programmed. Basal rates are set for periods of open loop therapy. When Auto Mode is not enabled, the user may use the Smart Guard™ Low Management features. Here, basal rate delivery will be suspended either when the SG has reached a programmed low threshold (Suspend on Low) or before the SGV has reached the programmed low threshold (Suspend before Low). At the start of the RCT, participants randomized to intervention group will receive face-to-face education at the study site by trained study staff (research nurses with diabetes knowledge who are insulin pump education specialists) based on the manufacturer's user guides. The initial educational session will take approximately 5-6 hours, including the device set-up of the pump. Participants’ pump data will be automatically uploaded to CareLinkTM through the MiniMed™ Clinical mobile phone app, which will be installed on participants’ phones and is connected with the pump via Bluetooth. The app uploads data every 24 hours into the cloud, 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. Remote reviews will happen daily for 7 days after initiation of AHCL, then weekly for 6 weeks, then monthly until the end of the RCT phase. During the extension phase, remote reviews will be performed every 2 months. Personalised pump setting changes/refinements can be insulin basal rates and insulin-to-carbohydrate-ratios, if required, and will be verified by the investigative staff by way of electronic review of the pump upload with the new settings.
Sponsors
University of Otago
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
7 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female aged 7 – 25 years inclusive. 2. Type I diabetes as per the American Diabetes Association Classification, diagnosed at least 1 year prior to Study Day 1. 3. Current HbA1c level of greater than or equal to 8.5% (69mmol/mol). 4. Minimum daily insulin requirement of greater than or equal to 8 units of insulin/day. 5. Willing and able to adhere to the study protocol. 6. Access to the internet and a computer system that meets requirements for uploading the study pump.
Exclusion criteria
1. Previous use of closed loop technology prior to Baseline visit. 2. 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. 3. Use of a medication indicative of moderate/severe diabetes complications (ACE inhibitors and statins are permitted). 4. Use of systemic glucocorticoids within 2 weeks prior to the Baseline visit. 5. Current use of Metformin, SGLT-2 or GLP-1 medications. 6. History or current evidence of severe psychiatric disorder, uncontrolled seizure disorder, renal impairment or cardiovascular disease (including uncontrolled hypertension), that in the opinion of the Investigator would limit study involvement or be a safety issue. 7. For diabetic retinopathy (DR) or other visual impairment, the following criteria apply: A. Nil or Minimal retinopathy (less than or equal to R1/M1) – no restriction on study entry. To follow established ISPAD screening guidelines as below. B. If Grade 1 / Mild retinopathy (R2/M2) and HbA1c less than 10% (86mmol/mol) – no restriction to study entry. C. If Grade 1 / Mild retinopathy (R2/M2) and HbA1c equal to or greater than 10% (86mmol/mol) – DR screening to be performed during the study pre-screening phase (not greater than 4 weeks prior to initiation of blinded CGM). If subject remains at Grade 1 / Mild retinopathy (R2/M2) and frequency of screening is equal to or more than 1 year (indicating less clinical concern), subject meets inclusion. If subject has progressed to Moderate (Grade 2) or Severe (Grade 3) DR, to be excluded as per below exclusion criteria. D. Absolute exclusion: Any DR classed as Moderate (Grade 2) or Severe (Grade 3) non-proliferative retinopathy (known as equal to or more than R3/M3) is exclusive. NB: ISPAD guidelines (2022) for who needs retinopathy screening to be followed while in study care. These are: Screening from age 11 years with 2-5years diabetes duration. Subsequent monitoring frequency 2-3 yearly (or as locally recommended/available). E. History of severe visual impairment (which in the opinion of the Investigator would limit their successful involvement), is exclusive. 8. If female, is pregnant or plans to become pregnant while participating in the study. A positive urine pregnancy test at Screening is exclusionary. 9. Any clinically significant concomitant disease or 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.
Outcome results
None listed