Closed Loop From Onset in Type 1 Diabetes

NCT02871089 | Active Not Recruiting DMC

• 1 other identifier: CLOuD
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 7

Brief 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

Keywords

Type 1 Diabetes; Closed-loop glucose control; Artificial Pancreas; Continuous subcutaneous insulin infusion; Multiple daily injection therapy; New onset type 1 diabetes; Residual C-Peptide secretion; Beta-cell function preservation; Continuous glucose monitoring

Outcome Measures

Primary Outcomes (1)

• Area under the meal stimulated C-peptide curve (AUC) during a mixed meal tolerance test (MMTT)

  12 months post diagnosis

Secondary Outcomes (16)

• Mean stimulated C-peptide AUC during a mixed meal tolerance test

  Baseline, 6 months and 24 months post diagnosis

• HbA1c Levels

  Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis

• Percentage of patients in each group with HbA1c <7.5% (58mmol/mol)

  Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis

• Percentage of time spent with sensor glucose readings in the target range (3.9 to 10mmol/l)

  Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis

• Mean sensor glucose level

  Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis

Other Outcomes (10)

• Severe hypoglycaemic episodes

  24 month intervention period

• Diabetes ketoacidosis

  24 month intervention period

• Adverse Events

  24 month intervention period + 3 weeks

Study Arms (2)

24/7 Closed loop delivery

EXPERIMENTAL

Unsupervised home use of day and night automated closed-loop insulin delivery system FlorenceM (Medtronic 640G insulin pump, guardian 3 CGM and Android smartphone) of CamAPS FX (Dana insulin pump, Dexcom G6 CGM and App on Android smartphone) until 24 months after diagnosis

Device: Closed-loop system (Florence M or CamAPS FX)

Multiple Daily Injections

ACTIVE COMPARATOR

Participants will apply standard insulin therapy using multiple daily injections via insulin pens during the 24 months control period

Other: Multiple Daily Injections

Interventions

Closed-loop system (Florence M or CamAPS FX) DEVICE

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).

24/7 Closed loop delivery

Multiple Daily Injections OTHER

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.

Multiple Daily Injections

Eligibility Criteria

• Age: 10 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of type 1 diabetes within previous 21 days. Day 1 will be defined as the day insulin was first administered. Type 1 diabetes will be defined according to WHO criteria using standard diagnostic practice.
• \[WHO definition: 'The aetiological type named type 1 encompasses the majority of cases with are primarily due to beta-cell destruction, and are prone to ketoacidosis. Type 1 includes those cases attributable to an autoimmune process, as well as those with beta-cell destruction for which neither an aetiology nor a pathogenesis is known (idiopathic). It does not include those forms of beta-cell destruction or failure to which specific causes can be assigned (e.g. cystic fibrosis, mitochondrial defects, etc.).'\]
• The subject is at least 10 years and not older than 16.9 years
• The subject/carer is willing to perform regular capillary blood glucose monitoring, with at least 4 blood glucose measurements taken every day
• The subject is literate in English
• The subject is willing to wear glucose sensor
• The subject is willing to wear closed loop system at home
• The subject is willing to follow study specific instructions
• The subject is willing to upload pump and CGM data at regular intervals

You may not qualify if:

• Physical or psychological condition likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
• Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc.
• Known or suspected allergy to insulin
• Regular use of acetaminophen
• Lack of reliable telephone facility for contact
• Pregnancy, planned pregnancy, or breast feeding
• Living alone
• Severe visual impairment
• Severe hearing impairment
• Medically documented allergy towards the adhesive (glue) of plasters or unable to tolerate tape adhesive in the area of sensor placement
• Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located at places of the body, which potentially are possible to be used for localisation of the glucose sensor
• Illicit drugs abuse
• Prescription drugs abuse
• Alcohol abuse
• Sickle cell disease, haemoglobinopathy, receiving red blood cell transfusion or erythropoietin within 3 months prior to time of screening

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: collaborator
• University of Cambridge: lead
• Alder Hey Children's NHS Foundation Trust: collaborator
• Nottingham University Hospitals NHS Trust: collaborator
• Oxford University Hospitals NHS Trust: collaborator
• University Hospital Southampton NHS Foundation Trust: collaborator
• Jaeb Center for Health Research: collaborator
• The Leeds Teaching Hospitals NHS Trust: collaborator
• University of Edinburgh: collaborator

Study Sites (7)

Southampton Children's Hospital

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Nottingham Children's Hospital

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, West Derby, L12 2AP, United Kingdom

Location

St James's University Hospital

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Royal Hospital for Sick Children

Edinburgh, EH9 1LF, United Kingdom

Location

Related Publications (7)

• Hovorka R. Artificial Pancreas Project at Cambridge 2013. Diabet Med. 2015 Aug;32(8):987-92. doi: 10.1111/dme.12766. Epub 2015 Apr 15.

  PMID: 25819473 BACKGROUND

• Thabit H, Tauschmann M, Allen JM, Leelarathna L, Hartnell S, Wilinska ME, Acerini CL, Dellweg S, Benesch C, Heinemann L, Mader JK, Holzer M, Kojzar H, Exall J, Yong J, Pichierri J, Barnard KD, Kollman C, Cheng P, Hindmarsh PC, Campbell FM, Arnolds S, Pieber TR, Evans ML, Dunger DB, Hovorka R. Home Use of an Artificial Beta Cell in Type 1 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2129-2140. doi: 10.1056/NEJMoa1509351. Epub 2015 Sep 17.

  PMID: 26379095 BACKGROUND

• Tauschmann M, Allen JM, Wilinska ME, Thabit H, Stewart Z, Cheng P, Kollman C, Acerini CL, Dunger DB, Hovorka R. Day-and-Night Hybrid Closed-Loop Insulin Delivery in Adolescents With Type 1 Diabetes: A Free-Living, Randomized Clinical Trial. Diabetes Care. 2016 Jul;39(7):1168-74. doi: 10.2337/dc15-2078. Epub 2016 Jan 6.

  PMID: 26740634 BACKGROUND

• Boughton CK, Allen JM, Ware J, Wilinska ME, Hartnell S, Thankamony A, Randell T, Ghatak A, Besser REJ, Elleri D, Trevelyan N, Campbell FM, Sibayan J, Calhoun P, Bailey R, Dunseath G, Hovorka R; CLOuD Consortium. Closed-Loop Therapy and Preservation of C-Peptide Secretion in Type 1 Diabetes. N Engl J Med. 2022 Sep 8;387(10):882-893. doi: 10.1056/NEJMoa2203496.

  PMID: 36069870 DERIVED

• Rankin D, Kimbell B, Allen JM, Besser REJ, Boughton CK, Campbell F, Elleri D, Fuchs J, Ghatak A, Randell T, Thankamony A, Trevelyan N, Wilinska ME, Hovorka R, Lawton J. Adolescents' Experiences of Using a Smartphone Application Hosting a Closed-loop Algorithm to Manage Type 1 Diabetes in Everyday Life: Qualitative Study. J Diabetes Sci Technol. 2021 Sep;15(5):1042-1051. doi: 10.1177/1932296821994201. Epub 2021 Jul 14.

  PMID: 34261348 DERIVED

• Rankin D, Kimbell B, Hovorka R, Lawton J. Adolescents' and their parents' experiences of using a closed-loop system to manage type 1 diabetes in everyday life: qualitative study. Chronic Illn. 2022 Dec;18(4):742-756. doi: 10.1177/1742395320985924. Epub 2021 Jan 20.

  PMID: 33472409 DERIVED

• Boughton C, Allen JM, Tauschmann M, Hartnell S, Wilinska ME, Musolino G, Acerini CL, Dunger PD, Campbell F, Ghatak A, Randell T, Besser R, Trevelyan N, Elleri D, Northam E, Hood K, Scott E, Lawton J, Roze S, Sibayan J, Kollman C, Cohen N, Todd J, Hovorka R; CLOuD Consortium. Assessing the effect of closed-loop insulin delivery from onset of type 1 diabetes in youth on residual beta-cell function compared to standard insulin therapy (CLOuD study): a randomised parallel study protocol. BMJ Open. 2020 Mar 12;10(3):e033500. doi: 10.1136/bmjopen-2019-033500.

  PMID: 32169925 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Roman Hovorka, PhD

  Department of Paediatrics, University of Cambridge, UK

  STUDY DIRECTOR

• Ajay Thankamony, MD

  Department of Paediatrics, University of Cambridge, UK

  PRINCIPAL INVESTIGATOR

• Atrayee Ghatak, MD

  Alder Hey Children's NHS Foundation Trust, Liverpool

  PRINCIPAL INVESTIGATOR

• Tabitha Randell, MD

  Nottingham Children's Hospital, Nottingham, UK

  PRINCIPAL INVESTIGATOR

• Rachel Besser, MD

  Oxford Children's Hospital, Oxford, UK

  PRINCIPAL INVESTIGATOR

• Nicola Trevelyan, MD

  Southampton Children's Hospital, Southampton, UK

  PRINCIPAL INVESTIGATOR

• Daniela Elleri, MD

  Royal Hospital for Sick Children, Edinburgh, UK

  PRINCIPAL INVESTIGATOR

• Fiona Campbell, MD

  Leeds Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research

Study Record Dates

• First Submitted: July 27, 2016
• First Posted: August 18, 2016
• Study Start: January 1, 2017
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2024
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (7)