The Artificial Pancreas in Very Young Children With T1D - Pilot (KidsAP01)

NCT03101865 | Completed DMC

• 1 other identifier: KidsAP01
• Study Type: interventional
• Target: 24
• Locations: 4 countries
• Sites: 7

Brief Summary

The suggested clinical trial is part of the KidsAP project funded by the European Commission's Horizon 2020 Framework Programme. The project evaluates the use of the Artificial Pancreas (or closed loop systems) in very young children with type 1 diabetes (T1D) aged 1 to 7 years. The suggested trial is a feasibility study to pilot the setup of a large-scale outcome trial and to address the specific needs of this population. The results of the pilot trial will feed into the design of the outcome study. In this study the investigators will compare closed loop insulin delivery using standard strength insulin to closed loop use with diluted insulin in very young children with T1D. Diluted insulin is a standard treatment approach for children with low insulin requirements. The investigators hypothesize that diluted insulin will lead to more stable glucose levels by reducing inaccuracies accentuated by delivery of minute amounts of insulin (frequently less than 0.1U/h \[1μl/h with standard strength insulin\] in small children compared to 1U/h in adults). These inaccuracies may result from pump plunger micro-jumps, tissues pressure build-up, and infusion set kinking. This study builds on previous and on-going studies of closed loop systems that have been performed in Cambridge in children and adolescents with T1D in clinical research facilities and in the home setting. The study adopts an open-label, multi-centre, multinational, randomised, two-period crossover design contrasting closed loop glucose control using diluted insulin and closed loop using standard insulin strength under free-living home conditions. The two intervention periods will last 3 weeks each with a 1 to 4 weeks washout period in between. The order of the two interventions will be random. A total of up to 30 young children aged 1 to 7 years with T1D on insulin pump therapy will be recruited through outpatient diabetes clinics at participating clinical centres to allow for 24 completed subjects available for assessment in each of the study arms. Prior to the use of study devices, participants and parents/guardians will receive appropriate training by the research team on the safe use of the study pump and continuous glucose monitoring system, and the hybrid closed loop insulin delivery system. Carers at nursery or school may also receive training by the study team if required. During the intervention periods, subjects and parents/guardians will use the closed loop system for 21 days under free-living conditions in their home and nursery/school environment without remote monitoring or supervision by research staff. The primary outcome is time spent in target range between 3.9 and 10.0 mmol/l as recorded by CGM. Secondary outcomes are the time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises the tabulation of severe hypoglycaemic episodes.

Conditions

Type 1 Diabetes Mellitus

Keywords

Type 1 diabetes; Artificial Pancreas; Closed-loop glucose control; Very young children; Continuous subcutaneous insulin infusion; Continuous glucose monitoring

Outcome Measures

Primary Outcomes (1)

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

  Percentage of time spent with sensor glucose readings in the target glucose range from 3.9 to 10.0 mmol// (70 to 180 mg/dl)

  3-week home stay

Secondary Outcomes (12)

• Time spent below target glucose (3.9mmol/l)(70mg/dl)

  3-week home stay

• Time spent above target glucose (10.0mmol/l) (180mg/dl)

  3-week home stay

• Average glucose

  3-week home stay

• Standard deviation of glucose levels

  3-week home stay

• Coefficient of variation of glucose levels

  3-week home stay

Other Outcomes (6)

• Number of episodes of severe hypoglycaemia

  3-week home stay

• Number of subjects experiencing severe hypoglycaemia

  3-week home stay

• Frequency of diabetic ketoacidosis

  3-week home stay

Study Arms (2)

Closed loop with diluted insulin

EXPERIMENTAL

Unsupervised home use of day and night automated closed loop insulin delivery system (FlorenceM) combined with pump suspend feature using DILUTED insulin aspart over 3 weeks.

Device: FlorenceM

Closed loop with standard insulin strength

ACTIVE COMPARATOR

Unsupervised home use of day and night automated closed loop insulin delivery system (FlorenceM) combined with pump suspend feature using STANDARD strength insulin aspart over 3 weeks.

Device: FlorenceM

Interventions

FlorenceM DEVICE

The automated closed loop system (FlorenceM) will consist of: Next generation sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Enlite 3 family 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.

Closed loop with diluted insulin; Closed loop with standard insulin strength

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 of age (inclusive)
• Type 1 diabetes as defined by WHO for at least 6 months
• 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
• Treated with rapid acting insulin analogue insulin Aspart (Novo Nordisk, Bagsvaerd, Denmark)
• Subject/carer is willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements taken every day
• Screening HbA1c ≤ 11% (97mmol/mol)
• Willing to wear glucose sensor
• Willing to wear closed loop system 24/7
• 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
• Known or suspected allergy to insulin
• Recurrent incidents of severe hypoglycaemia (\>2 episodes) during the previous 6 months \[severe hypoglycaemia is defined as an event associated with a seizure or loss of consciousness\]
• Unwilling to avoid regular use of acetaminophen
• Carer's lack of reliable telephone facility for contact
• Total daily insulin dose ≥ 2 IU/kg/day
• 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) or German (Germany, Austria, Luxembourg) or French (Luxembourg)

Sponsors & Collaborators

• University of Cambridge: lead
• European Commission: collaborator
• Medtronic: 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

Study Sites (7)

Department of Pediatrics and Adolescent Medicine, Medical University of Graz

Graz, A-8036, Austria

Location

Department of Pediatrics I, Medical University of Innsbruck

Innsbruck, A-6020, Austria

Location

Deptartment of Pediatrics, Medical University of Vienna

Vienna, A-1090, Austria

Location

Division for Paediatric Diabetology, University of Leipzig

Leipzig, D-04103, Germany

Location

Clinique Pédiatrique de Luxembourg

Luxembourg, L-1210, Luxembourg

Location

University of Cambridge

Cambridge, 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

• Ruan Y, Elleri D, Allen JM, Tauschmann M, Wilinska ME, Dunger DB, Hovorka R. Pharmacokinetics of diluted (U20) insulin aspart compared with standard (U100) in children aged 3-6 years with type 1 diabetes during closed-loop insulin delivery: a randomised clinical trial. Diabetologia. 2015 Apr;58(4):687-90. doi: 10.1007/s00125-014-3483-6. Epub 2014 Dec 24.

  PMID: 25537835 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

• Tauschmann M, Allen JM, Nagl K, Fritsch M, Yong J, Metcalfe E, Schaeffer D, Fichelle M, Schierloh U, Thiele AG, Abt D, Kojzar H, Mader JK, Slegtenhorst S, Barber N, Wilinska ME, Boughton C, Musolino G, Sibayan J, Cohen N, Kollman C, Hofer SE, Frohlich-Reiterer E, Kapellen TM, Acerini CL, de Beaufort C, Campbell F, Rami-Merhar B, Hovorka R; KidsAP Consortium. Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Very Young Children: A Multicenter, 3-Week, Randomized Trial. Diabetes Care. 2019 Apr;42(4):594-600. doi: 10.2337/dc18-1881. Epub 2019 Jan 28.

  PMID: 30692242 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

Study Officials

• Roman Hovorka, PhD

  Department of Paediatrics, University of Cambridge, UK

  STUDY DIRECTOR

• Carlo Acerini, MD

  Department of Paediatrics, University of Cambridge, UK

  PRINCIPAL INVESTIGATOR

• Carine de Beaufort, PhD

  Clinique Pédiatrique de Luxembourg, University of Luxembourg, Luxembourg

  PRINCIPAL INVESTIGATOR

• Fiona Campbell, MD

  St James's University Hospital, Leeds, UK

  PRINCIPAL INVESTIGATOR

• Elke Fröhlich-Reiterer, MD

  Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria

  PRINCIPAL INVESTIGATOR

• Sabine Hofer, MD

  Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria

  PRINCIPAL INVESTIGATOR

• Thomas Kapellen, MD

  Division for Paediatric Diabetology, University of Leipzig, Leipzig, Germany

  PRINCIPAL INVESTIGATOR

• Birgit Rami-Merhar, MD

  Deptartment of Pediatrics, Medical University of Vienna, Vienna, Austria

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: April 5, 2017
• Study Start: August 8, 2017
• Primary Completion: May 11, 2018
• Study Completion: May 11, 2018
• Last Updated: June 6, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); GB (2); DE (1); LU (1)