Closing the Loop in Adults With Sub-optimally Controlled Type 1 Diabetes Under Free Living Conditions

Inclusion criteria

• The subject has type 1 diabetes as defined by WHO
• The subject is 18 years of age or older
• The subject will have been on an insulin pump for at least 6 months with good knowledge of insulin self-adjustment including carbohydrate counting
• The subject is treated with one of the rapid acting insulin analogues (Insulin Aspart, Insulin Lispro or Insulin Glulisine)
• HbA1c ≥7.5% (58mmol/mmol) and ≤ 10% (86 mmol/mmol) based on analysis from central laboratory or equivalent
• The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 6 measurements per day
• The subject is willing to wear closed-loop system at home and at work place
• The subject is willing to follow study specific instructions
• The subject is willing to upload pump and CGM data at regular intervals
• 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.

Exclusion criteria

• Non-type 1 diabetes mellitus
• Any other physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results
• 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
• More than one episode of severe hypoglycaemia as defined by American Diabetes Association (31) in preceding 6 months (Severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions).
• Random C-peptide > 100pmol/l with concomitant plasma glucose >4 mM(72 mg/dl)
• Total daily insulin dose > 2 IU/kg/day
• Subject is pregnant or breast feeding or planning pregnancy in near future (within next 3 months)
• Severe visual impairment
• Severe hearing impairment
• Subjects using implanted internal pacemaker
• Lack of reliable telephone facility for contact
• Subject not proficient in English (UK) or German (Germany and Austria)
• Subjects who are living alone

Additional exclusion criteria specific for Austria and Germany

• Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
• Positive alcohol breath test.

Additional exclusion criteria specific for Germany only

• Positive reaction to any of the following tests: hepatitis B surface (HBs) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus (HIV) 1 antibodies, anti-HIV2 antibodies.
• Significantly reduced hypoglycaemia awareness withGold score ≥ 4 according to Geddes J et al, Diabetes Care 2007
• Serious macro- and microangiopathy
• Serious anomalies of the skin
• Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located at places of the body, which potentially are possible to be used for localisation of the glucose sensor)
• Renal insufficiency
• Epilepsy
• Eating disorders (like bulimia or anorexia nervosa)
• Disorders of the lipid metabolism
• Blood transfusion requiring patients
• Psychiatric diseases and related conditions
• Patients with frequent catheter abscesses having occurred in connection with the pump therapy
• Patients with medically documented allergy towards the adhesive (glue) of plasters
• Abnormal blood values for:

• the creatinine clearance,
• erythropoietin,
• TSH.
• Patients with the following concomitant medications or misuse of substances:

• steroids,
• anticoagulant therapies.
• Patients with a planned intervention under general anaesthesia.
• Patients who do shift work