Clinical trial NCT04042207: Diabeloop for Highly Unstable Type 1 Diabetes
Official title: In Adults With Very Unstable Type 1 Diabetes, is the DBLHU Closed-Loop Insulin Delivery System Able to Improve Blood Glycemic Control Compared to Low-Glucose-Predictive-Suspend System: Two-center, Randomized, Open-label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Diabetes Mellitus, Brittle
Closed-Loop
Keywords: Artificial pancreas
Very Unstable Type 1 diabetes
Lead sponsor: Centre d'Etudes et de Recherche pour l'Intensification du Traitement du Diabète
Sponsor class: OTHER
First posted: 2019-08-01
Enrollment: 7
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: N-of-1 trials consists in a prospectively planned, multiple crossover study in a single individual.
Primary purpose: DEVICE_FEASIBILITY

Brief summary: 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

Primary outcomes:
measure: Percentage of CGM time in glucose range 70-180 mg/dl, during 24 hours periods for the third and fourth week for each treatment period
timeFrame: 14 days for each treatment period
Secondary outcomes:
measure: Evolution over time of the DBLHU system's performance on a day-to-day and determination of the optimization delay of glycemic control
timeFrame: Over twenty-four hour periods on the four weeks of each treatment period and of the 24-week and 48-week extented CL period.
measure: Percent of CGM time in glucose range 70-180 mg/dl during nighttime.
timeFrame: Overnight (defined as 00:00 to 06:00) periods on the third and fourth week of each treatment period and during the last 4 weeks of the 24-week and 48-week extented CL period.
measure: Percent of CGM time in glucose range 70-180 mg/dl during daytime.
timeFrame: Over daytime (defined as 06:00 to 00:00) periods on the third and fourth week of each treatment period and during the last 4 weeks of the 24-week and 48-week extented CL period.
measure: Percent of CGM time with glucose < 70mg/dl, < 60mg/dl, < 54mg/dl and < 50mg/dl
timeFrame: Over twenty-four hour periods on the third and fourth weeks of each treatment period and during the last 4 weeks of the 24-week and 48-week extented CL period.
measure: Percent of CGM time with glucose > 180mg/dl, > 250mg/dl, > 300mg/dl and > 360mg/dl
timeFrame: Over twenty-four hour periods on the third and fourth weeks of each treatment period and during the last 4 weeks of the 24-week and 48-week extented CL period.
measure: Average glycemia level
timeFrame: Over twenty-four hour periods on the third and fourth weeks of each treatment period and during the last 4 weeks of the 24-week and 48-week extented CL period.
measure: Estimated HbA1c (eHbA1c) levels / glucose management indicator (GMI)
timeFrame: Over twenty-four hour periods on the third and fourth weeks of each treatment period and during the last 4 weeks of the 24-week and 48-week extented CL period.
measure: HbA1c levels
timeFrame: HbA1c value at the week 24 and week 48 of extented CL period.
measure: Glucose coefficient of variation (CV) and Standard deviation (SD)
timeFrame: Over twenty-four hour periods on the third and fourth weeks of each treatment period and during the last 4 weeks of the 24-week and 48-week extented CL period.
measure: Rate of CGM excursions below 54 mg/dl (3.0 mM) for at least 15 min
timeFrame: Over twenty-four hour periods on the third and fourth weeks of each treatment period and during the last 4 weeks of the 24-week and 48-week extented CL period.
measure: Comparison of MAGE index and Low Blood Glucose Index (LBGI)
timeFrame: Over twenty-four hour periods on the third and fourth weeks of each treatment period and during 24-week extension period
measure: Number of acute metabolic events (severe hypoglycemia, severe Diabetic Ketoacidosis [DKA])
timeFrame: During 4 weeks of each treatment period and during 24-week and 48-week extension period
measure: Number of severe hypoglycemia with loss of consciousness
timeFrame: During 4 weeks of each treatment period and during 24-week and 48-week extension period
measure: Number of hospitalizations for severe hypoglycemia or ketoacidosis
timeFrame: During 4 weeks of each treatment period and during 24-week and 48-week extension period
measure: For the use and the acceptance, a satisfaction survey will be done on the daily management of diabetes, the modification of daily life with the system dan the fear of hypoglycemia
timeFrame: after baseline period (2-week); after crossover period; after 24-week and after 48-week extension period
measure: Percentage of CGM time in glucose range 70-180 mg/dl, during 24 hours periods
timeFrame: 24-week and 48-week extension period
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Grenoble Alpes University Hospital
city: Lille
country: France
facility: Lille University Hospital
Study officials:
affiliation: University Hospital, Grenoble
name: Pierre Yves BENHAMOU, Pr
role: PRINCIPAL_INVESTIGATOR
References: