Closing the Loop in People with Type 1 Diabetes

NCT05653050 | Completed DMC

• 1 other identifier: CLEAR Phase 2
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 4

Brief Summary

The main objective of this study is to determine whether home use of fully closed-loop glucose control applying age-approved ultra-rapid insulin (Phase 2) is superior to standard insulin pump therapy with continuous glucose monitoring (CGM) in adolescents with type 1 diabetes on insulin pump therapy with sub-optimal glycaemic control (HbA1c ≥ 7.5% \[Phase 2\]). This is an open-label, multi-centre, randomised, crossover design study, involving a run-in period followed by two study periods during which glucose levels will be controlled either by an automated closed-loop system using age-approved ultra-rapid insulin or by participants' usual insulin pump therapy with continuous glucose monitoring in random order. A total of up to 30 adolescents (aiming for 24 completed participants) with T1D on insulin pump therapy will be recruited through diabetes clinics and other established methods. Participants will receive appropriate training in the safe use of the closed-loop devices. Participants will have access to the study team during the home study phase with 24/7 telephone support. The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by CGM over the 8 week period. Secondary outcomes are HbA1c, time spent with glucose levels above and below target as recorded by CGM, and other CGM-based metrics in addition to insulin requirements. Safety evaluation comprises severe hypoglycaemic episodes, diabetic ketoacidosis (DKA) events and other adverse and serious adverse events.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (1)

• Time in target glucose range

  Time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on continuous glucose monitoring (CGM)

  8-week home use

Secondary Outcomes (8)

• Time spent above the target glucose range

  8-week home use

• Time spent below the target glucose range

  8-week home use

• Mean glucose

  8-week home use

• Standard deviation and coefficient of variation of glucose

  8-week home use

• Time spent in hypoglycaemia

  8-week home use

Other Outcomes (9)

• Safety evaluation

  8-week home use

• Safety evaluation

  8-week home use

• Safety evaluation

  8-week home use

Study Arms (2)

Fully closed-loop system with age-approved ultra-rapid insulin

EXPERIMENTAL

The fully closed-loop system (CamAPS HX) will consist of: * Mylife YpsoPump insulin pump (Ypsomed, Burgdorf, Switzerland). * Freestyle Libre 3 real-time CGM sensor (Abbott, Diabetes Care, CA, USA) * Android smartphone hosting CamAPS HX App with the Cambridge model predictive control algorithm. * Cloud upload system to review CGM/insulin data. Participants will use ultra-rapid insulin aspart in the closed-loop system.

Device: CamAPS HX

Standard insulin pump therapy with CGM

ACTIVE COMPARATOR

Participants will use their own insulin pump and usual insulin throughout this study period. The CGM will be the Freestyle Libre 3 real-time CGM sensor (Abbott, Diabetes Care, CA, USA).

Device: Standard insulin pump therapy with CGM

Interventions

CamAPS HX DEVICE

Fully automated closed-loop system (CamAPS HX) with ultra-rapid insulin aspart.

Fully closed-loop system with age-approved ultra-rapid insulin

Standard insulin pump therapy with CGM DEVICE

Participants usual insulin pump therapy with Freestyle Libre 3 CGM

Standard insulin pump therapy with CGM

Eligibility Criteria

• Age: 13 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• The participant has type 1 diabetes as defined by WHO for at least 1 year
• The participant is aged 13 to 19 years (inclusive) (Phase 2)
• The participant will have been on an insulin pump for at least 3 months with good knowledge of insulin self-adjustment
• The participant is treated with one of the rapid acting or ultra-rapid acting insulin analogues (Insulin Aspart, faster acting insulin Aspart, Insulin Lispro, ultra-rapid Lispro insulin or Insulin Glulisine) 6. HbA1c ≥7.5% (58mmol/mol) based on analysis from local laboratory 7. The participant is willing to wear closed-loop devices 8. The participant is willing to follow study specific instructions 9. Female participants of child bearing age must have a negative urine-HCG pregnancy test at screening and should be using effective contraception if sexually active.

You may not qualify if:

• Any physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results
• Known or suspected allergy against insulin
• Total daily insulin dose more than or equal to 2 IU/kg/day
• Use of a closed-loop system within the past 30 days
• Participant is pregnant or breast feeding or planning pregnancy within next 12 months
• Severe visual impairment
• Severe hearing impairment
• Lack of reliable telephone facility for contact
• Participant not proficient in English

Sponsors & Collaborators

• University of Cambridge: lead
• Manchester University NHS Foundation Trust: collaborator
• Barts & The London NHS Trust: collaborator
• Norfolk and Norwich University Hospitals NHS Foundation Trust: collaborator

Study Sites (4)

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Barts Health NHS Trust

London, United Kingdom

Location

Manchester Royal Infirmary

Manchester, United Kingdom

Location

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, United Kingdom

Location

Related Publications (1)

• Kadiyala N, Allen J, Lakshman R, Boughton CK, Wilinska ME, Thankamony A, Hartnell S, Thabit H, Willemsen RH, Shah P, Ware J, Hovorka R. Lived experience of fully closed-loop insulin delivery in adolescents with type 1 diabetes and HbA1c above target. Diabetes Res Clin Pract. 2025 Dec 30;232:113078. doi: 10.1016/j.diabres.2025.113078. Online ahead of print.

  PMID: 41478508 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Continuous Glucose Monitoring

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; Investigative Techniques

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: Professor

Model Details: An open-label, multi-centre, randomised, two-period, crossover study comparing fully closed-loop glucose control to standard insulin pump therapy combined with continuous glucose monitoring

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: December 16, 2022
• Study Start: February 20, 2023
• Primary Completion: September 30, 2024
• Study Completion: October 15, 2024
• Last Updated: December 6, 2024

Record last verified: 2024-12

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 (4)