FASter Insulin in Closed-loop Technology in Children

NCT04759144 | Completed DMC

• 1 other identifier: FAST-Kids
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

The main objective of this study is to determine whether 24/7 hybrid closed-loop insulin delivery under free living conditions applying faster insulin aspart (FiAsp) is superior to 24/7 hybrid closed-loop insulin delivery applying standard insulin aspart in very young children with type 1 diabetes. The closed-loop system consists of three components: the continuous glucose monitor (CGM), the insulin pump and a smartphone Application, or App, that translates, in real-time, sensor glucose levels received from the glucose monitoring device and calculates the amount of insulin to be delivered by the coupled insulin pump. This is a double-blind, multi-centre, randomised, crossover design study, involving a run-in period followed by two 8-week study periods during which glucose levels will be controlled by a hybrid closed-loop system using either standard insulin aspart or faster insulin aspart in random order. Participants aged 2-6 years with type 1 diabetes on insulin pump therapy will be recruited through paediatric diabetes outpatient clinics at participating clinical centres. Enrolment will target up to 30 children (aiming for 6-14 participants per centre) to allow for dropouts during run-in. 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 CGM device, and the hybrid closed-loop insulin delivery system. Parents/guardians at nursey/school may also receive training by the study team if required. Participants will have regular contact with the study team during the study including 24/7 telephone support. Parents/guardians will be asked to complete validated questionnaires at the start and end of the study to assess quality of life measures including sleep. The primary outcome is the between group difference in time spent in target range between 3.9 and 10.0 mmol/l as recorded by CGM during the study. Secondary outcomes are time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises assessment of the frequency and severity of hypoglycaemic episodes and diabetic ketoacidosis (DKA).

Conditions

Type 1 Diabetes Mellitus

Keywords

Faster insulin aspart; Closed loop insulin delivery

Outcome Measures

Primary Outcomes (1)

• Time in target (3.9 to 10.0mmol/L) (70 to 180 mg/dL)

  Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM)

  8-week intervention

Secondary Outcomes (15)

• Time spent above target glucose (10.0 mmol/L) (180 mg/dL)

  8-week intervention

• Mean glucose

  8-week intervention

• Time spent below target glucose (3.9 mmol/L) (70 mg/dL)

  8-week intervention

• Standard deviation of glucose

  8-week intervention

• Coefficient of variation of glucose

  8-week intervention

Study Arms (2)

Faster insulin aspart with hybrid closed-loop insulin delivery

ACTIVE COMPARATOR

Unsupervised home use of hybrid closed-loop insulin delivery with faster insulin aspart for 8 weeks. Intervention: Use of faster insulin aspart with hybrid closed-loop insulin delivery

Device: CamAPS FX using faster insulin aspart

Standard insulin aspart with hybrid closed-loop insulin delivery

ACTIVE COMPARATOR

Unsupervised home use of hybrid closed-loop insulin delivery with standard insulin aspart for 8 weeks. Intervention: Use of standard insulin aspart with hybrid closed-loop insulin delivery

Device: CamAPS FX using standard insulin aspart

Interventions

CamAPS FX using faster insulin aspart 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

Faster insulin aspart with hybrid closed-loop insulin delivery

CamAPS FX using standard insulin aspart 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

Standard insulin aspart with hybrid closed-loop insulin delivery

Eligibility Criteria

• Age: 2 Years - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age between 2 and 6 years (inclusive)
• 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 parent/guardian good knowledge of insulin self-adjustment as judged by the investigator
• Treated with U-100 rapid or ultra-rapid acting insulin analogue
• Screening HbA1c ≤ 11% (97mmol/mol) on analysis from local laboratory
• Able to wear glucose sensor
• Able to wear closed-loop system 24/7
• The parent/guardian is willing to follow study specific instructions
• The parent/guardian is proficient in English

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
• Parent/guardian's lack of reliable telephone facility for contact
• Parent/guardian's severe visual impairment
• Parent/guardian'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)

Sponsors & Collaborators

• University of Cambridge: lead
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• Oxford University Hospitals NHS Trust: collaborator
• Nottingham University Hospitals NHS Trust: collaborator
• Alder Hey Children's NHS Foundation Trust: collaborator

Study Sites (2)

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

Related Publications (6)

• Tauschmann M, Thabit H, Bally L, Allen JM, Hartnell S, Wilinska ME, Ruan Y, Sibayan J, Kollman C, Cheng P, Beck RW, Acerini CL, Evans ML, Dunger DB, Elleri D, Campbell F, Bergenstal RM, Criego A, Shah VN, Leelarathna L, Hovorka R; APCam11 Consortium. Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a multicentre, 12-week randomised trial. Lancet. 2018 Oct 13;392(10155):1321-1329. doi: 10.1016/S0140-6736(18)31947-0. Epub 2018 Oct 3.

  PMID: 30292578 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 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

• Dovc K, Boughton C, Tauschmann M, Thabit H, Bally L, Allen JM, Acerini CL, Arnolds S, de Beaufort C, Bergenstal RM, Campbell F, Criego A, Dunger DB, Elleri D, Evans ML, Frohlich-Reiterer E, Hofer S, Kapellen T, Leelarathna L, Pieber TR, Rami-Merhar B, Shah VN, Sibayan J, Wilinska ME, Hovorka R; APCam11, AP@Home, and KidsAP Consortia. Young Children Have Higher Variability of Insulin Requirements: Observations During Hybrid Closed-Loop Insulin Delivery. Diabetes Care. 2019 Jul;42(7):1344-1347. doi: 10.2337/dc18-2625. Epub 2019 May 21.

  PMID: 31221700 BACKGROUND

• Musolino G, Dovc K, Boughton CK, 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, Ashcroft N, Wilinska ME, 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. Reduced burden of diabetes and improved quality of life: Experiences from unrestricted day-and-night hybrid closed-loop use in very young children with type 1 diabetes. Pediatr Diabetes. 2019 Sep;20(6):794-799. doi: 10.1111/pedi.12872. Epub 2019 Jun 13.

  PMID: 31140654 BACKGROUND

• Ware J, Allen JM, Boughton CK, Cezar A, Hartnell S, Wilinska ME, Thankamony A, Deakin M, Leyland H, Phelan K, Thornborough K, Hovorka R. Hybrid Closed-Loop with Faster Insulin Aspart Compared with Standard Insulin Aspart in Very Young Children with Type 1 Diabetes: A Double-Blind, Multicenter, Randomized, Crossover Study. Diabetes Technol Ther. 2023 Jun;25(6):431-436. doi: 10.1089/dia.2023.0042.

  PMID: 36880866 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

  Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: An unmasked member of staff will undertake randomisation. The participants and the clinical staff will be blind to allocated treatment sequence.
• 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 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. Treatment: Two insulins will be used * Faster insulin aspart (Fiasp) * Standard insulin aspart (Novorapid)

Study Record Dates

• First Submitted: February 13, 2021
• First Posted: February 18, 2021
• Study Start: March 12, 2021
• Primary Completion: September 14, 2022
• Study Completion: December 1, 2022
• Last Updated: March 14, 2023

Record last verified: 2023-03

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

GB (2)