Closing the Loop in People With Type 1 Diabetes (CLEAR Phase 2)

Purpose of clinical trial:

To determine whether home use of fully closed-loop applying age-approved ultra-rapid insulin is superior to insulin pump therapy with continuous glucose monitoring (CGM).

Study objectives:

The study objective is to compare home use of fully closed-loop glucose control applying ultra-rapid Lispro insulin (Phase 1) or age-approved ultra-rapid insulin (Phase 2) with standard insulin pump therapy with CGM.

1. EFFICACY: The objective is to assess the efficacy of fully closed-loop glucose control applying ultra-rapid Lispro insulin (Phase 1) or age-approved ultra-rapid insulin (Phase 2) in maintaining CGM glucose levels within the target range from 3.9 to 10.0 mmol/l, as compared to standard insulin pump therapy combined with CGM.
2. SAFETY: The objective is to evaluate the safety of fully closed-loop glucose control in terms of episodes of severe hypoglycaemia, hyperglycaemia and other adverse events and adverse device effects.
3. UTILITY: The objective is to determine the percentage of time when closed-loop was operational, and usability and acceptance of the closed-loop system.

Participating clinical centres:

1. Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
2. Diabetes, Endocrine & Metabolism Centre, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester
3. The Royal London Children's Hospital of Whitechapel Road, Barts Health NHS Trust, London

Sample Size:

24 adolescents completing the study. Up to 30 for phase 2 will be recruited to allow for dropouts.

Maximum duration of study for a participant:

20 weeks (5 months)

Recruitment:

The participants will be recruited through the young adult and paediatric diabetes outpatient clinics or other established methods.

Consent:

Participants and/or parents/guardians will be asked to provide written informed consent/assent.

Baseline Assessment:

Eligible participants will undergo a baseline evaluation including a blood sample for the measurement of HbA1c, renal, liver functions, full blood count, thyroid functions and coeliac antibody screen (if not done in the previous 6 months). Urine pregnancy test will be done in females of child bearing age. Human factor questionnaires will be administered.

Run-in Period:

During the 2-3 week run-in period, participants will use their own insulin pump and wear a masked CGM system. At the end of the run-in period, for compliance, at least 10 days of CGM data need to be recorded. CGM data during the run-in period will be used to assess baseline glucose control before the start of the first home study phase.

Randomisation:

Eligible participants will be randomised using randomisation software to the use of closed-loop glucose control or to standard pump therapy with CGM. There will be no washout period between the two intervention periods.

1. Automated closed-loop:

   Training on the use of closed-loop will be provided by the research team during a 2 to 3 hour session in an outpatient setting (clinical research facility) or may be done remotely/at home. Competency on the use of study insulin pump, study CGM and closed-loop system will be evaluated using a competency assessment tool developed by the research team. Further training may be delivered as required. Participants will be advised to use the closed-loop system with age-approved ultra-rapid insulin for the next 8 weeks.

2. Conventional insulin pump therapy with CGM:

Participants will use their own insulin pump and study CGM. Training on the use of real-time CGM and how to interpret real-time will be provided. Participants will use standard insulin pump therapy, with their usual insulin, and real-time CGM for the next 8 weeks.

Cross-over Assessment:

At the end of the first intervention period, a blood sample for the measurement of HbA1c will be taken and human factor questionnaires will be administered.

End of study assessments:

A blood sample will be taken for measurement of HbA1c and human factor questionnaires will be administered. Study devices will be returned and participants will resume usual care.

Procedures for safety monitoring during trial:

Standard operating procedures for monitoring and reporting of all adverse events and adverse device events will be in place, including serious adverse events (SAE), serious adverse device effects (SADE) and specific adverse events (AE) such as severe hypoglycaemia.

A data monitoring and ethics committee (DMEC) will be informed of all serious adverse events and any unanticipated adverse device/method effects that occur during the study and will review compiled adverse event data at periodic intervals.

Criteria for withdrawal of patients on safety grounds:

A participant may terminate participation in the study at any time without necessarily giving a reason and without any personal disadvantage. An investigator can stop the participation of a subject after consideration of the benefit/risk ratio. Possible reasons are:

• Serious adverse events
• Significant protocol violation or non-compliance
• Failure to satisfy competency assessment
• Decision by the investigator, or the sponsor, that termination is in the participant's best medical interest
• Pregnancy, planned pregnancy, or breast feeding
• Allergic reaction to insulin
• Technical grounds (e.g. participant relocates)