The Artificial Pancreas in Very Young Children With T1D

NCT03784027 | Completed Results DMC

• 1 other identifier: KidsAP02
• Study Type: interventional
• Target: 81
• Locations: 4 countries
• Sites: 8

Brief Summary

The suggested clinical trial is part of the KidsAP project funded by the European Commission's Horizon 2020 Framework Programme and JDRF. It evaluates the use of the Artificial Pancreas (closed loop system) in very young children with type 1 diabetes (T1D) aged 1-7 years. This outcome study aims to determine whether 24/7 automated closed loop glucose control improves time in range compared to sensor augmented pump therapy. An extension phase will evaluate the effect of long-term home use of the 24/7 automated hybrid closed loop insulin delivery system on glucose control (UK sites only). The study employs an open-label, multi-centre, multi-national, randomized, two-period, crossover design. Participants undergo a 2-4 week run-in period, followed by two 16-week treatment periods (one for each therapy) separated by a 1-4 week washout. The order of treatments is randomized. Up to 80 young children (with a target of 72 randomized subjects) on insulin pump therapy will be recruited from paediatric outpatient diabetes clinics. Before using the study devices, participants and their parents/guardians receive training on the safe use of the study pump, continuous glucose monitoring (CGM) device, and hybrid closed loop system. Nursery or school carers may also be trained if needed. During the closed loop arm, subjects use the system for 16 weeks under free-living conditions at home and in nursery/school without remote monitoring. In the control arm, subjects use sensor augmented pump therapy for 16 weeks under similar conditions, with regular contact and 24/7 telephone support from the study team. The primary endpoint is the time spent in the target glucose range (3.9-10.0 mmol/l) as recorded by CGM. Secondary outcomes include the time spent with glucose levels above and below target and other CGM metrics. Safety assessments include the frequency and severity of hypoglycaemic episodes and diabetic ketoacidosis (DKA). In the extension phase, participants have follow-up contacts every 3 months, with the primary endpoint measured over 18 months from the end of the primary phase and compared to sensor augmented pump therapy during that phase. Secondary outcomes, safety, and utility will be assessed similarly.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Time in Target (3.9 to 10.0 mmol/l) (70 to 180 mg/dl)

  Between group difference in time spent with sensor glucose levels between 3.9 to 10.0 mmol/l (70 to 180 mg/dl) during the 4 months intervention period.

  16-week home stay

Secondary Outcomes (19)

• Key Endpoint: Time Spent Above Target Glucose (10.0 mmol/l) (180 mg/dl)

  16-week home stay

• Key Endpoint: HbA1c

  16-week home stay

• Key Endpoint: HbA1c

  16 weeks

• Key Endpoint: Mean Sensor Glucose

  16-week home stay

• Key Endpoint: Time Spent Below Target Glucose (3.9 mmol/l) (70 mg/dl)

  16-week home stay

Study Arms (2)

Automated closed loop insulin delivery (intervention arm)

EXPERIMENTAL

Unsupervised home use of day and night automated hybrid closed loop insulin delivery system over 16 weeks. Intervention: Device: CamAPS FX

Device: CamAPS FX

Sensor augmented pump therapy (control arm)

ACTIVE COMPARATOR

Sensor augmented pump therapy over 16 weeks.

Other: Sensor augmented therapy

Interventions

CamAPS FX DEVICE

CamAPS FX closed loop system comprises: * Dana insulin pump (Diabecare, Sooil, Seoul, South Korea) * Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) * An Android smartphone hosting CamAPS FX app with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump and glucose sensor * Cloud upload system to monitor CGM/insulin data

Automated closed loop insulin delivery (intervention arm)

Sensor augmented therapy OTHER

Study insulin pump and study CGM.

Sensor augmented pump therapy (control arm)

Eligibility Criteria

• Age: 1 Year - 7 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age between 1 and 7 years (inclusive) (Luxembourg and Austria)
• Age between 2 and 7 years (inclusive) (Germany and UK)
• Type 1 diabetes as defined by WHO for at least 6 months \[WHO definition: 'The aetiological type named type 1 encompasses the majority of cases which are primarily due to beta-cell destruction, and are prone to ketoacidosis. Type 1 includes those cases attributable to an autoimmune process, as well as those with beta-cell destruction for which neither an aetiology nor a pathogenesis is known (idiopathic). It does not include those forms of beta-cell destruction or failure to which specific causes can be assigned (e.g. cystic fibrosis, mitochondrial defects, etc.).'\]
• Insulin pump user (with or without continuous glucose monitoring or flash glucose monitoring system) for at least 3 months, with subject/carer good knowledge of insulin self-adjustment as judged by the investigator
• On sensor-augmented pump as standard clinical care (extension phase only)
• Treated with rapid or ultra-rapid acting insulin analogue
• Subject/carer is willing to perform regular finger-prick blood glucose monitoring, with at least 2 blood glucose measurements taken every day
• Screening HbA1c ≤ 11% (97mmol/mol) on analysis from local laboratory
• Willing to wear glucose sensor
• Willing to wear closed loop system 24/7 during intervention arm
• The subject/carer is willing to follow study specific instructions
• The subject/carer is willing to upload pump and CGM data at regular intervals

You may not qualify if:

• Physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
• Untreated coeliac disease or thyroid disease based on local investigations prior to study enrolment
• Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids
• Use of closed loop insulin delivery within the past 2 months
• Known or suspected allergy to insulin
• Carer's lack of reliable telephone facility for contact
• Subject/carer's severe visual impairment
• Subject/carer's severe hearing impairment
• Medically documented allergy towards the adhesive (glue) of plasters or subject is unable to tolerate tape adhesive in the area of sensor placement
• Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located in parts of the body which could potentially be used for localisation of the glucose sensor)
• Sickle cell disease, haemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
• Plan to receive red blood cell transfusion or erythropoietin over the course of study participation
• Subject/carer not proficient in English (UK, Germany, Austria, Luxembourg) or German (Germany, Austria, Luxembourg) or French (Luxembourg)
• Known microvascular diabetes complications (retinopathy, renal disease, neuropathy)
• Eating disorders

Sponsors & Collaborators

• University of Cambridge: lead
• European Commission: collaborator
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• The Leeds Teaching Hospitals NHS Trust: collaborator
• University of Luxembourg: collaborator
• University of Leipzig: collaborator
• Medical University of Graz: collaborator
• Medical University Innsbruck: collaborator
• Medical University of Vienna: collaborator
• Jaeb Center for Health Research: collaborator
• University of Edinburgh: collaborator
• Stanford University: collaborator
• Glooko: collaborator

Study Sites (8)

Medical University of Graz Department of Pediatrics and Adolescent Medicine

Graz, A-8036, Austria

Location

Medical University of Innsbruck Department of Pediatrics I

Innsbruck, A-6020, Austria

Location

Medical University of Vienna Department of Pediatrics

Vienna, A-1090, Austria

Location

University of Leipzig Division for Paediatric Diabetology

Leipzig, D-04103, Germany

Location

Clinique Pédiatrique de Luxembourg Centre Hospitalier de Luxembourg

Luxembourg, L-1210, Luxembourg

Location

University Department of Paediatrics

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Related Publications (6)

• Elleri D, Allen JM, Tauschmann M, El-Khairi R, Benitez-Aguirre P, Acerini CL, Dunger DB, Hovorka R. Feasibility of overnight closed-loop therapy in young children with type 1 diabetes aged 3-6 years: comparison between diluted and standard insulin strength. BMJ Open Diabetes Res Care. 2014 Dec 11;2(1):e000040. doi: 10.1136/bmjdrc-2014-000040. eCollection 2014.

  PMID: 25512874 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

• Tauschmann M, Allen JM, Wilinska ME, Thabit H, Acerini CL, Dunger DB, Hovorka R. Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Suboptimally Controlled Adolescents With Type 1 Diabetes: A 3-Week, Free-Living, Randomized Crossover Trial. Diabetes Care. 2016 Nov;39(11):2019-2025. doi: 10.2337/dc16-1094. Epub 2016 Sep 9.

  PMID: 27612500 BACKGROUND

• Ware J, Allen JM, Boughton CK, Wilinska ME, Hartnell S, Thankamony A, de Beaufort C, Schierloh U, Frohlich-Reiterer E, Mader JK, Kapellen TM, Rami-Merhar B, Tauschmann M, Nagl K, Hofer SE, Campbell FM, Yong J, Hood KK, Lawton J, Roze S, Sibayan J, Bocchino LE, Kollman C, Hovorka R; KidsAP Consortium. Randomized Trial of Closed-Loop Control in Very Young Children with Type 1 Diabetes. N Engl J Med. 2022 Jan 20;386(3):209-219. doi: 10.1056/NEJMoa2111673.

  PMID: 35045227 DERIVED

• Fuchs J, Allen JM, Boughton CK, Wilinska ME, Thankamony A, de Beaufort C, Campbell F, Yong J, Froehlich-Reiterer E, Mader JK, Hofer SE, Kapellen TM, Rami-Merhar B, Tauschmann M, Hood K, Kimbell B, Lawton J, Roze S, Sibayan J, Cohen N, Hovorka R; KidsAP Consortium. Assessing the efficacy, safety and utility of closed-loop insulin delivery compared with sensor-augmented pump therapy in very young children with type 1 diabetes (KidsAP02 study): an open-label, multicentre, multinational, randomised cross-over study protocol. BMJ Open. 2021 Feb 12;11(2):e042790. doi: 10.1136/bmjopen-2020-042790.

  PMID: 33579766 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Prof Roman Hovorka
• Organization: University of Cambridge

rh347@cam.ac.uk

+44 1223 762 862

Study Officials

• Roman Hovorka

  Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Model Details: Device: CamAPS FX The automated closed loop system (CamAPS FX) will consist of: * Dana RS insulin pump (Diabecare, Sooil, Seoul, South Korea) * Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) * An Android smartphone hosting CamAPS FX app with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump and glucose sensor * Cloud upload system to monitor CGM/insulin data.

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: December 21, 2018
• Study Start: May 1, 2019
• Primary Completion: February 22, 2021
• Study Completion: October 3, 2022
• Last Updated: March 27, 2025
• Results First Posted: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication.
• Access Criteria: Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication.

Locations

DE (1); AU (3); GB (3); LU (1)