Diabeloop for Highly Unstable Type 1 Diabetes

Feasibility study, comparing experimental treatment (DBLHU closed-loop system) with reference treatment (Low Glucose Predictive Suspend system) in 7 patients going through a series of N-of-1 trials. Each N-of-1 trial consists in a prospectively planned, multiple crossover study in a single individual. Two blocks of two periods of four weeks each (closed loop or open loop) will be conducted. Within each block, the sequence closed loop-open loop or open loop-close loop is randomized. Outcomes will be analyzed on the third and fourth weeks of period.

A remote monitoring system managed by specialized nurse on behalf of diabetologist, is provided in closed-loop session.

An extension period of 48 weeks with the DBLHU System (closed-loop condition) will be performed at the end of the crossover study phase in real life conditions (without remote monitoring).


Eligibility Criteria:
Inclusion Criteria:

* Subject (aged 22 or more) with Type 1 diabetes for at least 5 years and confirmed C peptide negative
* Treated with continuous subcutaneous insulin infusion (CSII) for ≥ 6 months,
* Trained to carbohydrate counting/flexible insulin therapy,
* Subject that had experienced, despite optimal diabetes management and prior to any equipment with Smartguard technology, glucose instability as defined by at least 2 of the following criteria which would have led to eligibility for pancreatic islet transplantation:

  * occurrence of at least 1 severe hypoglycemic episode during the past 12 months (need for third party),
  * occurrence of ketoacidosis (hospitalization in ICU) without explanation
  * Impaired awareness of hypoglycemia (Clark Score ≥ 4; Gold Score \> 4)
  * glucose levels: standard deviation \> 50% of the arithmetic mean value on glucose meter or \> 40 mg/dl on CGM on a 14-day recording
  * glucose levels: MAGE (mean amplitude of glucose excursions) index \> 60 mg/dl
  * glucose levels: coefficient of variation (CV) \> 36%
* with persisting extreme glucose variability despite optimal medical care
* with contra-indication or no agreement to undertake pancreatic islet transplantation or pancreas transplantation.
* Subject willing to wear the DBLHU system continuously throughout the study

Exclusion Criteria:

* patient with type 2 diabetes
* age \< 22 years old
* patient without any social or familial support able to intervene in case of severe hypoglycemic event
* any permanent and severe condition able to interact with the normal course of the study
* patient with insulin-resistance defined by insulin requirements \> 1.5U/kg/d
* patient with a daily dose of insulin required greater than 90 units
* patient receiving a total daily dose of insulin less than 8 U
* use of any insulin that is not 100 U/mL fast-acting insulin analog
* patient suffering from a serious illness or a treatment that might significantly impair diabetes physiology, i.e. glucose-insulin interactions, that might interfere with the medical device (for example irregular treatment of steroids)
* patient having severe problems of uncorrected hearing and/or visual acuity
* patient who is unable to understand and perform all the instructions provided by Diabeloop SA
* patient not willing to perform ≥4 finger stick blood glucose measurements daily
* patients that have frequent exposure to magnetic resonance imaging (MRI), computed tomography (CT) scan, or high-frequency electrical heat (diathermy) treatment.
* patient who has had a pancreatectomy or who has pancreatic malfunctions
* patient having severely altered renal function (Creatinine clearance \< 30ml/min)
* patient on dialysis
* pregnancy or breast-feeding patient, or project of pregnancy during the next 6 months
* lack of effective contraception in women of childbearing potential
* all conditions excluding participation to clinical research as defined in France