Closing the Loop 24/7 in Adolescents With Type 1 Diabetes

The main objective of this study is to determine the efficacy, safety and utility of automated closed-loop glucose control in the home setting over a short term period, including the daytime and during the activities of normal daily living. This study builds on previous and on-going studies of closed-loop systems that have been performed in Cambridge in children and adolescents with type 1 diabetes in the clinical research facility and in the home setting. The data and experienced gained from this study will be utilised in planning future home studies.

This is an open-label, single-centre, randomised, crossover study, involving two, 7 day (phase 1) and 21 day (phase 2) home study periods during which glucose levels will be controlled either by an automated closed-loop system or by subjects' usual insulin pump therapy combined with continuous glucose monitoring in random order. A total of up to 30 children and adolescents aged 10 to 18 years with T1D on insulin pump therapy will be recruited through diabetes clinics, to allow for 12 completed subjects available for assessment in each study phase.

Subjects will receive appropriate training by the research team on the safe use of the closed-loop insulin delivery system. During the training visit in a clinical research centre, subjects will be encouraged to mimic their usual daily activities and will be allowed to walk inside hospital premises. Subjects will be advised to discontinue automated closed-loop insulin delivery and follow their usual insulin pump therapy for certain activities such as periods of strenuous exercise during the 7 day (phase 1) and 21 day (phase 2) home study phase.

The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by CGM (conservatively adjusted for potential over-estimation). 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.

Inclusion criteria

• The subject is between 10 and 18 years of age (inclusive)
• The subject has type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative
• The subject/carer will have been an insulin pump user for at least 3 months, with good knowledge of insulin self-adjustment as judged by the investigator
• The subject/carer is willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements taken every day
• HbA1c between 7.0% and 11.0 % (53 to 97mmol/mol) based on analysis from central laboratory or equivalent
• The subject is literate in English
• The subject is willing to wear closed-loop system at home and at school / college / work
• The subject is willing to follow study specific instructions

Exclusion criteria

• Non-type 1 diabetes mellitus including those secondary to chronic disease
• Any other physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator.
• Current treatment with drugs known to have significant interference with glucose metabolism, such as systemic corticosteroids, as judged by the investigator
• Known or suspected allergy against insulin
• Subjects with clinically significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator
• Significantly reduced hypoglycaemia awareness as judged by the investigator
• Total daily insulin dose ≥ 2 IU/kg/day
• Total daily insulin dose <10 IU/day
• Reduced hypoglycaemia awareness
• Pregnancy, planned pregnancy or breast feeding
• Severe visual impairment
• Severe hearing impairment
• Subjects using implanted internal pacemaker
• Lack of reliable telephone facility for contact