Diabeloop for Highly Unstable Type 1 Diabetes (DBLHU)

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

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).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1; Diabetes Mellitus, Brittle; Closed-Loop
• Intervention / Treatment: Device: Low Glucose Predictive Suspend system; Device: DBLHU System

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38700
    • Grenoble Alpes University Hospital
  • Lille, France, 59037
    • Lille University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DEVICE_FEASIBILITY
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Reference treatment (Open-Loop); Sensor-augmented pump therapy (SAP) namely the Low Glucose Predictive Suspend system or LGPS and a blinded glucose sensor (Dexcom G6) followed by a 48-week extension period in closed-loop condition	Device: Low Glucose Predictive Suspend system; consists of sensor-augmented pump therapy (SAP) / Low Glucose Predictive Suspend system (with predictive low glucose management technology); Other Names: Open-loop condition; Device: DBLHU System; DBLHU system embeds a regulation algorithm to automatically regulate the patient's glycaemia. It takes as input glycaemia value received every 5 minutes from the CGM and patient inputs related to meals and physical activities and it calculates the amount of insulin to be delivered. It sends this information to the pump that automatically delivers this quantity.; Other Names: Closed-loop condition
EXPERIMENTAL: DBLHU system (Closed-Loop); DBLHU software (a Model Predictive Control [MPC]-based glucose control algorithm) running on handset associated with the six-generation glucose sensor (Dexcom G6) and Kaleido insulin pump followed by a 48-week extension period in closed-loop condition	Device: DBLHU System; DBLHU system embeds a regulation algorithm to automatically regulate the patient's glycaemia. It takes as input glycaemia value received every 5 minutes from the CGM and patient inputs related to meals and physical activities and it calculates the amount of insulin to be delivered. It sends this information to the pump that automatically delivers this quantity.; Other Names: Closed-loop condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Measured by continuous glucose monitoring	14 days for each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution over time of the DBLHU system's performance on a day-to-day and determination of the optimization delay of glycemic control	Measured by continuous glucose monitoring	Over twenty-four hour periods on the four weeks of each treatment period and of the 24-week and 48-week extented CL period.
Percent of CGM time in glucose range 70-180 mg/dl during nighttime.	Measured by continuous glucose monitoring	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.
Percent of CGM time in glucose range 70-180 mg/dl during daytime.	Measured by continuous glucose monitoring	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.
Percent of CGM time with glucose < 70mg/dl, < 60mg/dl, < 54mg/dl and < 50mg/dl	Measured by continuous glucose monitoring	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.
Percent of CGM time with glucose > 180mg/dl, > 250mg/dl, > 300mg/dl and > 360mg/dl	Measured by continuous glucose monitoring	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.
Average glycemia level	Measured by continuous glucose monitoring	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.
Estimated HbA1c (eHbA1c) levels / glucose management indicator (GMI)	Measured by continuous glucose monitoring	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.
HbA1c levels	Measured by blood sampling	HbA1c value at the week 24 and week 48 of extented CL period.
Glucose coefficient of variation (CV) and Standard deviation (SD)	Measured by continuous glucose monitoring	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.
Rate of CGM excursions below 54 mg/dl (3.0 mM) for at least 15 min	Mean time spent in hypoglycaemia, defined as sensor glucose values of 54 mg/dL (3∙0 mmol/L) or lower for more than 15 min consecutively	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.
Comparison of MAGE index and Low Blood Glucose Index (LBGI)	Mean amplitude of glucose excursions and Low Glucose index as measured by continuous glucose monitoring	Over twenty-four hour periods on the third and fourth weeks of each treatment period and during 24-week extension period
Number of acute metabolic events (severe hypoglycemia, severe Diabetic Ketoacidosis [DKA])	Measured by continuous glucose monitoring. Number of severe hypoglycemia is defined as any event requiring third party assistance. DKA events. Subjects will be asked to measure blood ketone levels on if their interstitial glucose is above 300 mg/l beyond the usual timeframe following a meal, as part of the safety evaluation for hyperglycemia.	During 4 weeks of each treatment period and during 24-week and 48-week extension period
Number of severe hypoglycemia with loss of consciousness	Number of severe hypoglycemia with loss of consciousness	During 4 weeks of each treatment period and during 24-week and 48-week extension period
Number of hospitalizations for severe hypoglycemia or ketoacidosis	Number of hospitalizations	During 4 weeks of each treatment period and during 24-week and 48-week extension period
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	DTSQ satisfaction questionnaire, with scale from 6 to 0 where 0 is the worth and 6 the best outcome.	after baseline period (2-week); after crossover period; after 24-week and after 48-week extension period
Percentage of CGM time in glucose range 70-180 mg/dl, during 24 hours periods	Measured by continuous glucose monitoring	24-week and 48-week extension period

Collaborators and Investigators

• Sponsor: Centre d'Etudes et de Recherche pour l'Intensification du Traitement du Diabète
• Investigators: Principal Investigator: Pierre Yves BENHAMOU, Pr, University Hospital, Grenoble

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 3, 2019
• Primary Completion (ACTUAL): February 27, 2020
• Study Completion (ACTUAL): March 22, 2021

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (ACTUAL): August 1, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 10, 2021
• Last Update Submitted That Met QC Criteria: May 7, 2021
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Artificial pancreas; Very Unstable Type 1 diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2019-A01365-52

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No