Short term closed-loop glucose control in adults with type 1 diabetes

Research summary

Type 1 diabetes mellitus (T1D) is characterised by an absolute deficiency of insulin caused by immunologically-mediated damage to the beta cells in the pancreas and raised blood glucose levels. It is one of the commonest endocrine and metabolic conditions in both children and adults. It is estimated that approximately 285 million adults (5-15% type 1 diabetes) & 480,000 children (95% type 1 diabetes) worldwide suffer from diabetes. Recent reports suggest that incidence and prevalence of T1D is increasing in many countries, at least in the under 15 year age group with the predicted number of new cases of childhood diabetes in Europe increasing to 24 400 in 2020 from 15 000 in 2005. This younger age at onset means that complications appear at a younger age, and dependence on lifelong insulin imposes a heavy burden on patients as well as health services. A survey conducted by Royal College of Paediatrics & Child Health in UK established that there were 22,783 children and young people 0-17 years with diabetes in England on 1st January 2009 out of which 97% had type 1 diabetes.

The development of a closed-loop system that combines glucose monitoring with computer-based algorithm dictated insulin delivery, may provide further improvements in glycaemic control while reducing hypoglycaemia and ultimately represent a realistic treatment option for people with T1D. The vital component of such a system, also known as an artificial pancreas (AP), is a computer-based algorithm. The role of the control algorithm is to translate, in real-time, the information it receives from the CGM and to compute the amount of insulin to be delivered by the pump. The other components include a real-time continuous glucose monitor and an infusion pump to titrate and deliver insulin.

The main objective of this study is to determine the feasibility, efficacy and safety of automated closed-loop glucose control in the home setting over a short term period. The data and experienced gained from this study will be utilised in planning future home studies. This is an open-label, three centre, randomised, crossover design, involving two, 8 day (first day in the clinical research facility and seven days at home) study periods during which glucose levels will be controlled either by an automated closed-loop system or by subjects usual insulin pump therapy in random order. The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by CGM (adjusted for potential over-estimation) during home stay. Secondary outcomes are the time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics, and for the stay at the clinical research facility, time spent in the target range, above and below the target range as measured by plasma glucose.

A total of up to 24 adults (aiming for 18 completed subjects) aged 18 years and older with T1D on insulin pump therapy will be recruited through diabetes clinics and other established methods in participating centres. Subjects will receive appropriate training in the safe use of closed-loop insulin delivery system. During the 24 hour in-patient stay subjects will be encouraged to mimic their usual day 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 periods of strenuous exercise during the 7 day home study phase.

Main inclusion criteria

  1. The subject has type 1 diabetes as defined by WHO

  2. The subject is 18 years of age or older

  3. The subject will have been on an insulin pump for at least 3 months currently using insulin Aspart, with good knowledge of insulin self-adjustment including carbohydrate counting

  4. HbA1c ≤ 10 % based on analysis from local laboratory

  5. The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 6 measurements per day during the 7 day home phase of the study

  6. The subject is willing to wear closed-loop system at home and at work place

  7. The subject is willing to follow study specific instructions

  8. The subject is literate in English

  9. Female subjects of child bearing age should be on effective contraception and must have a negative urine-HCG pregnancy test at screening. In addition in Germany, women of childbearing potential must use a highly effective method of birth control, which is defined as those which result in a low failure rate (i.e. less than 1% per year) and must use two independent methods of contraception, e.g. diaphragm and spermicide-coated condom.

Main exclusion criteria

  1. Non-type 1 diabetes mellitus

  2. Any other physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results

  3. Current treatment with drugs known to have significant interference with glucose metabolism, such as systemic corticosteroids, as judged by the investigator

  4. Known or suspected allergy against insulin

  5. Subjects with clinically significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator

  6. Significantly reduced hypoglycaemia awareness as judged by the investigator

  7. Total daily insulin dose ≥ 2 IU/kg/day

  8. Subject is pregnant or breast feeding or planning pregnancy in near future (within next 3 months)

  9. Severe visual impairment

  10. Severe hearing impairment

  11. Subjects using implanted internal pacemaker

  12. Lack of reliable telephone facility for contact

Chief investigator

Prof Roman Hovorka

Contact details

Clinical Trials ManagerDr Paula Kareclas

Telephone: 01223 596473 | Email: [email protected]