Automated Closed-loop in Children and Adolescents With Type 1 Diabetes (APCam09)

February 28, 2017 updated by: Dr Roman Hovorka, University of Cambridge

An Open-label, Single-centre, Randomised, 2-period Cross-over Study to Assess the Efficacy and Safety of a Novel Automated Overnight Closed-loop Glucose Control System on Day 1 of Continuous Glucose Monitoring Sensor Insertion in Comparison to Day 3 to 4 After Sensor Insertion in Children and Adolescents With Type 1 Diabetes

People with type 1 diabetes need regular insulin injections or continuous delivery of insulin using a pump. Keeping blood sugars in the normal range is known to reduce long term complications. However, achieving treatment goals can be very difficult due to the risk of low glucose levels (hypoglycaemia). One solution is to use a system where the amount of insulin injected closely matches the blood sugar levels on a continuous basis. This can be achieved by what is known as a "closed loop system" where a small glucose sensor placed under the skin communicates with a computer containing an algorithm that drives a subcutaneous insulin pump. Previous studies conducted under carefully controlled clinical research facility environment, in Cambridge, United Kingdom, as well as several other centres have shown that closed-loop glucose control is superior to usual insulin pump therapy. The next logical step in the development pathway is to test closed loop systems in the home environment. An essential requirement for conducting closed-loop studies outside clinical research facility is an automated system where wireless data transmission takes place between the glucose sensor and insulin pump.

The purpose of the present study is to evaluate the efficacy and safety of automated overnight closed-loop, in children and adolescents with type 1 diabetes, using a novel system which has greatest potential for use in the home setting. The study will take place at a clinical research facility on two occasions, using a standardised protocol. The performance of the closed-loop system will be evaluated on day 1 of continuous glucose monitoring (CGM) sensor life as compared to on days 3 to 4 of sensor life. Data and experience gained from this study will be used for further refinements and development of the system for future home use.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The main objective of the current study is to evaluate the efficacy, safety and utility/reliability of a novel automated overnight closed-loop glucose control system in children and adolescents with type 1 diabetes. This will inform the future development of closed-loop systems in children and adolescents aged 6 to 18 years with type 1 diabetes.

This is an open-label, randomised, 2-period cross-over study, using the Medtronic Android closed loop platform or similar, comparing the safety and efficacy of overnight closed loop glucose control on day 1 compared with day 3 to 4 of CGM sensor life. Participants will be randomised to undergo two overnight studies in a clinical research facility, during which glucose levels will be controlled by the computer-based closed-loop algorithm on day 1 of CGM sensor insertion or day 3 to 4 after sensor insertion.

A total of 16 children and adolescents with T1D between 6 and 18 years of age will be recruited through the Outpatient Diabetes Clinic in the Department of Paediatrics, Addenbrooke's Hospital and Paediatric Diabetes Centres in London, Norwich, and Ipswich, to allow for 12 available for assessment. All participants will be on insulin pump treatment with a good knowledge of insulin dose adjustments. The study will take place at the Wellcome Trust Clinical Research Facility (WTCRF), Cambridge. Participants will be admitted at the clinical research facility in the evening and stay until the following morning. During the two closed-loop visits, automated closed-loop glucose control with wireless data transmission will be performed. A Model-Predictive-Control algorithm will determine the insulin infusion rate based on interstitial glucose measured by a continuous subcutaneous glucose monitoring (CGM) system. Intravenous sampling for glucose and insulin levels will also be carried out on both study visits for post hoc validation of glucose sensor data and for future modelling purposes.

The primary efficacy endpoint is the time spent in the target plasma glucose range from 3.9 to 8 mmol/L. Safety evaluation is focused on the frequency and duration of episodes of hypoglycaemia.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • University of Cambridge

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The subject is between 6 and 18 years of age.
  • The subject has had type 1 diabetes, as defined by WHO criteria for at least 1 year or is confirmed C-peptide negative.
  • The subject will have been an insulin pump user for at least 3 months, with a good knowledge of insulin dose adjustment.
  • HbA1c between below 11 % based on analysis from central laboratory.
  • The subject is literate in English.
  • The subject is willing to undertake all study related activities.

Exclusion Criteria:

  • Non-type 1 diabetes mellitus including those secondary to chronic disease.
  • Any other physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results.
  • Current treatment with drugs known to interfere with glucose metabolism such as systemic corticosteroids, non-selective beta-blockers and MAO inhibitors.
  • Known or suspected allergy against insulin.
  • Subjects with clinically significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator
  • Patient is pregnant, or breast feeding during the period of the study.
  • Total daily insulin dose ≥ 2 Units/kg/day
  • Total daily insulin dose < 10 Units/day
  • Severe visual impairment
  • Severe hearing impairment
  • Subjects using implanted internal pacemaker

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Closed-loop on day 1 of CGM sensor life
Glucose level is controlled by the automated closed-loop glucose control system on day 1 after CGM sensor insertion.
Device: Closed-loop (Android Closed-Loop platform)

The closed-loop system is purpose-built and comprises a hand-held computer containing a model predictive control (MPC) based glucose control algorithm and communicating with the CGM device and the insulin pump.

The Android Closed-Loop platform employs the Medtronic MiniMed Paradigm® Veo™ insulin pump system with CGM capability (use of MiniLink™Transmitter and sensor). A Radiofrequency (RF) translator module translates the RF protocol to Bluetooth® technology. An Android device containing an algorithm will use sensor glucose data to calculate pump strokes.
Active Comparator: Closed-loop on day 3 of CGM sensor life
Glucose level is controlled by the automated closed-loop glucose control system on day 3 or 4 after CGM sensor insertion.
Device: Closed-loop (Android Closed-Loop platform)

The closed-loop system is purpose-built and comprises a hand-held computer containing a model predictive control (MPC) based glucose control algorithm and communicating with the CGM device and the insulin pump.

The Android Closed-Loop platform employs the Medtronic MiniMed Paradigm® Veo™ insulin pump system with CGM capability (use of MiniLink™Transmitter and sensor). A Radiofrequency (RF) translator module translates the RF protocol to Bluetooth® technology. An Android device containing an algorithm will use sensor glucose data to calculate pump strokes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time spent with plasma glucose concentration in the target glucose range from 3.9 to 8.0 mmol/l.
Time Frame: 10 hours
The primary outcome measure is time spent with plasma glucose concentration in the target range (3.9-8.0mmol/L) between 21:30 on Day 1 and 07:30 on Day 2 (10 hours), as obtained with closed-loop insulin delivery on day 1 of CGM sensor insertion as compared with closed-loop insulin delivery on day 3 to 4 of CGM sensor insertion.
10 hours

Secondary Outcome Measures

Outcome Measure
Time Frame
Time spent with plasma glucose concentration below the target range (<3.9mmol/L) between 21:30 on Day 1 and 07:30 on Day 2 (10 hours).
Time Frame: 10 hours
10 hours
Time spent with plasma glucose concentration above the target range (>8mmol/L) between 21:30 on Day 1 and 07:30 on Day 2 (10 hours).
Time Frame: 10 hours
10 hours
Mean and standard deviation of plasma glucose levels between 21:30 on Day 1 and 07:30 on Day 2 (10 hours).
Time Frame: 10 hours
10 hours
Total insulin delivery between 21:30 on Day 1 and 07:30 on Day 2 (10 hours).
Time Frame: 10 hours
10 hours
Total basal insulin delivery between 21:30 on Day 1 and 07:30 on Day 2 (10 hours).
Time Frame: 10 hours
10 hours
Plasma insulin concentrations between 21:30 on Day 1 and 07:30 on Day 2 (10 hours).
Time Frame: 10 hours
10 hours
Absolute relative difference between matched pairs of subcutaneous glucose sensor and reference plasma glucose.
Time Frame: 10 hours
10 hours

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of time the system is functioning as intended in active closed-loop mode.
Time Frame: 14 hours
Reliability / utility evaluation
14 hours
CGM failure (defined as no CGM glucose available for whatever reason; failure rate )
Time Frame: 14 hours
Reliability / utility evaluation
14 hours
Problems with user interface / Android platform (failure rate)
Time Frame: 14 hours
Reliability / utility evaluation
14 hours
Loss of communication between different system components (failure rate)
Time Frame: 14 hours
Reliability / utility evaluation
14 hours
number of episodes of hypoglycaemia (plasma glucose ≤ 3.5mmol/l)
Time Frame: 14 hours
Safety Evaluation
14 hours
number of episodes of hypoglycaemia (plasma glucose ≤ 2.8mmol/l)
Time Frame: 14 hours
Safety evaluation
14 hours
number of subjects experiencing hypoglycaemia
Time Frame: 14 hours
Safety evaluation
14 hours
nature and severity of any other adverse events
Time Frame: 14 hours
Safety evaluation
14 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cambridge

Collaborators

Cambridge University Hospitals NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

April 23, 2014

First Submitted That Met QC Criteria

May 1, 2014

First Posted (Estimate)

May 2, 2014

Study Record Updates

Last Update Posted (Actual)

March 3, 2017

Last Update Submitted That Met QC Criteria

February 28, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APCam09

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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