Closed Loop From Onset in Type 1 Diabetes

Summary

The purpose of the study is to use a novel treatment approach, the artificial pancreas, after diagnosis of type 1 diabetes (T1D) to improve glucose control with the anticipated improvements of residual C-peptide secretion.

This is an open-label, multicentre, single-period, randomised, parallel group design study. It is expected that a total of up to 190 subjects (aiming for 96 randomised subjects) will be recruited within ten working days of diagnosis of type 1 diabetes through paediatric diabetes centres in the UK. Half of the participants aged 10 to 16.9 years will be treated by conventional insulin injections and the other half by the artificial pancreas (closed loop insulin delivery system). Each treatment will last 24 months. All participants completing the 24 month study period will be invited to continue in an optional extension phase with the treatment allocated at randomisation for a further 24 months.

Subjects in the intervention group will receive additional training on components of the artificial pancreas, i.e. insulin pump and continuous glucose monitoring (CGM), prior to starting closed loop insulin delivery. Subjects in the control intervention group will continue with standard therapy, i.e. multiple daily injection therapy. The study includes up to 14 visits and 1 telephone/email contact for subjects completing the study. After run-in and randomisation, visits will be conducted every 3 months in both arms. Beta-cell function will be assessed by serial measurement of C-peptide in response to a standardised mixed meal tolerance test (MMTT). MMTTs will be conducted at baseline, 6-,12- and 24 months post diagnosis.

The primary outcome is the between group difference in the area under the stimulated C-peptide curve (AUC) of the MMTT at 12 month post diagnosis. Secondary outcomes include between group differences in stimulated C-peptide AUC over 24 months, differences in glycaemic control as assessed by HbA1c, time spent in glucose target range, glucose variability, hypo- and hyperglycaemia as recorded by periodically applied CGM, as well as insulin requirements and change in bodyweight. Additionally, cognitive, emotional and behavioural characteristics of participating subjects and parents will be assessed, and a cost utility analysis on the benefits of closed loop insulin delivery will be performed. Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes, diabetic ketoacidosis (DKA) and number, nature and severity of other adverse events.

Conditions

• Diabetes Mellitus
• Type 1 Diabetes

Interventions

DEVICE

Closed-loop system (Florence M or CamAPS FX)

The automated closed-loop system (FlorenceM) will consist of: * Sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Enlite/Guardian 3 real time CGM and glucose suspend feature. * An Android smartphone containing the Cambridge model predictive algorithm and communicating wirelessly with the insulin pump using a proprietary translator device. The automated closed-loop system (CamAPS FX) will consist of: * Dana R or RS insulin pump * Dexcom G6 real-time CGM * CamAPS FX App on an unlocked android smartphone. Rapid acting insulin analogue will be used (insulin aspart, insulin lispro, insulin glulisine or similar or ultra-rapid insulin analogue).

OTHER

Multiple Daily Injections

Rapid acting insulin analogue and long acting insulin analogue will be subcutaneously administered using CE-marked insulin pen devices in accordance with the manufacturer's instructions for their intended purposes. Participants will be given long acting analogue (insulin glargine, insulin detemir or similar) once or twice daily according to their needs and boluses of rapid acting analogue (insulin aspart, insulin lispro, insulin glulisine or similar or ultra-rapid insulin analogue) when carbohydrates are consumed.

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust

  collaborator OTHER

• Alder Hey Children's NHS Foundation Trust

  collaborator OTHER

• Nottingham University Hospitals NHS Trust

  collaborator OTHER

• Oxford University Hospitals NHS Trust

  collaborator OTHER

• University Hospital Southampton NHS Foundation Trust

  collaborator OTHER

• Jaeb Center for Health Research

  collaborator OTHER

• The Leeds Teaching Hospitals NHS Trust

  collaborator OTHER

• University of Edinburgh

  collaborator OTHER

• University of Cambridge

  lead OTHER

Principal Investigators

• Roman Hovorka, PhD · Department of Paediatrics, University of Cambridge, UK

• Ajay Thankamony, MD · Department of Paediatrics, University of Cambridge, UK

• Atrayee Ghatak, MD · Alder Hey Children's NHS Foundation Trust, Liverpool

• Tabitha Randell, MD · Nottingham Children's Hospital, Nottingham, UK

• Rachel Besser, MD · Oxford Children's Hospital, Oxford, UK

• Nicola Trevelyan, MD · Southampton Children's Hospital, Southampton, UK

• Daniela Elleri, MD · Royal Hospital for Sick Children, Edinburgh, UK

• Fiona Campbell, MD · Leeds Children's Hospital

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

10 Years

Max Age

16 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-01-31

Primary Completion

2023-07-31

Completion

2024-07-31

Countries

• United Kingdom

Study Locations