Home Testing of Day and Night Closed Loop With Pump Suspend Feature

Overview

The main study objective is to determine whether day and night automated closed loop glucose control combined with pump suspend feature will improve glucose control and reduce the burden of hypoglycaemia compared to sensor augmented insulin pump therapy alone. This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a three-month period of home study during which day and night glucose levels will be controlled either by a closed loop system combined with pump suspend feature (intervention group) or by sensor augmented insulin pump therapy (control group). It is expected that up to 100 subjects, aiming for 84 randomised subjects \[42 youth (6 to 21 years), and 42 adults (22 years and older)\], with type 1 diabetes will be recruited through paediatric and adult outpatient diabetes clinics in each of the investigation centres. Subjects who drop out within the first four weeks of the intervention may be replaced. Participants will all be on subcutaneous insulin pump therapy and will have proven competencies both in the use of the study insulin pump and the study CGM device. Subjects in the intervention group will receive appropriate training in the safe use of closed loop insulin delivery system and pump suspend feature. All subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is between group differences in the time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on CGM glucose levels during the 12 week free living phase. Secondary outcomes are HbA1 at the end of treatment period, the 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 of severe hypoglycaemic episodes.

Purpose of the study: To determine whether day and night automated closed loop glucose control combined with pump suspend feature will improve glucose control as measured by glycated haemoglobin and reduce the burden of hypoglycaemia compared to sensor augmented insulin pump therapy. Study objectives: 1. EFFICACY: The objective is to assess efficacy of day and night automated closed loop glucose control combined with pump suspend feature in maintaining glucose levels within the target range from 3.9 to 10.0mmol/l (70 to 180mg/dl) based on subcutaneous continuous glucose monitoring (CGM), as compared to sensor augmented insulin pump therapy. 2. SAFETY: The objective is to evaluate the safety of day and night automated closed loop glucose control combined with pump suspend feature, in terms of episodes of severe hypoglycaemia and other adverse events. 3. UTILITY: The objective is to determine the frequency and duration of the use of the automated closed loop system. 4. PSYCHOSOCIAL: Subjects' and family members' perception in terms of life-style change, diabetes management and fear of hypoglycaemia will be assessed using validated questionnaires and semi-structured qualitative interviews. Cognitive functions will be assessed using validated computerized cognitive tests. Study design: An open-label, multi-centre, multi-national, randomised, single-period, parallel group study, contrasting day and night automated closed loop glucose control combined with pump suspend feature with sensor augmented insulin pump therapy Population: 84 participants randomised (42 youth and 42 adults). Each centre will aim to recruit between 05 and 20 participants. Maximum duration of study for a subject : 18 weeks Recruitment: The subjects will be recruited through the paediatric and adult diabetes outpatient clinics at each centre. Consent: Written consent/assent will be obtained from participants and/or guardians according to REC/IRB requirements. Screening assessment: Eligible participants will undergo a screening evaluation where blood samples for full blood count, renal, liver, thyroid function and anti-transglutaminase antibodies with IgA levels will be taken (if not done in the previous 3 months). Random C-peptide, glucose and HbA1c will also be measured, and a urine pregnancy test in females of child-bearing potential. Questionnaires investigating participants' quality of life, psychosocial functioning and response to their current treatment will be distributed. Cognitive assessment will be made using validated computerized cognitive tests. Study Training: Training sessions on the use of study CGM, insulin pump (and closed loop system for those randomised to the intervention group) will be provided by the research team. Training session on the use of real-time CGM and on how to interpret real-time and retrospective stored data will be provided to all subjects/carers using written material. Run-in Period: During a 4 week run-in period, subjects will use study CGM and insulin pump. The research team will contact subject once weekly during the run-in period, and subjects will also be able to contact the research team for support and treatment optimisation as necessary. For compliance and to assess the ability of the subject to use the CGM and study pump safely, at least 12 days of CGM data need to be recorded and safe use of study insulin pump demonstrated during the last 14 days of run-in period. Competency assessment: Competency on the use of study insulin pump and study CGM will be evaluated using a competency assessment tool developed by the research team. Further training may be delivered as required. Randomisation: Eligible subjects will be randomised using randomisation software to the use of real-time CGM and pump suspend feature combined with day and night closed loop or to sensor augmented insulin pump therapy. 1. Automated day and night closed loop insulin delivery (intervention arm) combined with pump suspend feature (interventional arm): At the start, a blood sample will be taken for the measurement of HbA1c and a urine pregnancy test in females of child-bearing potential. A subset of participants will be interviewed to enable their historical diabetes management practices, everyday work and family lives, and their initial expectations of using closed loop technology to be captured and explored in-depth. Subjects will be admitted to the clinical facility on Day 1. Training on the use of closed loop and pump suspend feature will be provided by the research team. During the next 2-4 hours patient will operate the system under the supervision of the clinical team. Competency on the use of closed loop system will be evaluated. Subjects will use closed loop and pump suspend feature for 12 weeks. 2. Sensor augmented insulin pump therapy (control arm): A blood sample will be taken for the measurement of HbA1c and a urine pregnancy test in females of child-bearing potential. Subjects will use sensor augmented insulin pump therapy without pump suspend feature for 12 weeks. End of study assessments: * A blood sample will be taken for measurement of HbA1c. * Validated questionnaires evaluating the impact of the devices employed on life change, diabetes management will be completed. * Cognitive assessment will be made using validated computerized cognitive tests. * Follow-up interviews will be undertaken with the subset of participants/family members at the end of the closed loop intervention. Procedures for safety monitoring during trial: * Standard operating procedures for monitoring and reporting of all adverse events will be in place, including serious adverse events (SAE), serious adverse device effects (SADE) and specific adverse events (AE) such as severe hypoglycaemia. * Subjects will be asked to test and record blood or urine ketones if their finger prick glucose is above 14.0mmol/l (250mg/dl) in the morning on waking, as part of the safety assessment for hyperglycaemia. * A data safety and monitoring board (DSMB) will be informed of all serious adverse events and any unanticipated serious adverse device 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 subject, parent, or guardian 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: 1. Serious adverse events 2. Significant protocol violation or non-compliance 3. Failure to satisfy competency assessment 4. Decision by the investigator, or the sponsor, that termination is in the subject's best medical interest 5. Pregnancy, planned pregnancy, or breast feeding 6. Allergic reaction to insulin 7. Technical grounds (e.g. subject relocates)