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Diabeloop for Highly Unstable Type 1 Diabetes (DBLHU)

Primary Purpose

Diabetes Mellitus, Type 1, Diabetes Mellitus, Brittle, Closed-Loop

Status

Completed

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Low Glucose Predictive Suspend system

DBLHU System

About this trial

This is an interventional device feasibility trial for Diabetes Mellitus, Type 1 focused on measuring Artificial pancreas, Very Unstable Type 1 diabetes

Eligibility Criteria

22 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Grenoble Alpes University Hospital
Lille University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Reference treatment (Open-Loop)

DBLHU system (Closed-Loop)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Percent of CGM time in glucose range 70-180 mg/dl during nighttime.

Measured by continuous glucose monitoring

Percent of CGM time in glucose range 70-180 mg/dl during daytime.

Measured by continuous glucose monitoring

Percent of CGM time with glucose < 70mg/dl, < 60mg/dl, < 54mg/dl and < 50mg/dl

Measured by continuous glucose monitoring

Percent of CGM time with glucose > 180mg/dl, > 250mg/dl, > 300mg/dl and > 360mg/dl

Measured by continuous glucose monitoring

Average glycemia level

Measured by continuous glucose monitoring

Estimated HbA1c (eHbA1c) levels / glucose management indicator (GMI)

Measured by continuous glucose monitoring

HbA1c levels

Measured by blood sampling

Glucose coefficient of variation (CV) and Standard deviation (SD)

Measured by continuous glucose monitoring

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

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

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.

Number of severe hypoglycemia with loss of consciousness

Number of hospitalizations for severe hypoglycemia or ketoacidosis

Number of hospitalizations

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.

Percentage of CGM time in glucose range 70-180 mg/dl, during 24 hours periods

Measured by continuous glucose monitoring

Full Information

NCT ID

NCT04042207

First Posted

July 19, 2019

Last Updated

May 7, 2021

Sponsor

Centre d'Etudes et de Recherche pour l'Intensification du Traitement du Diabète

1. Study Identification

Unique Protocol Identification Number

NCT04042207

Brief Title

Diabeloop for Highly Unstable Type 1 Diabetes

Acronym

DBLHU

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

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

September 3, 2019 (Actual)

Primary Completion Date

February 27, 2020 (Actual)

Study Completion Date

March 22, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre d'Etudes et de Recherche pour l'Intensification du Traitement du Diabète

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 1, Diabetes Mellitus, Brittle, Closed-Loop

Keywords

Artificial pancreas, Very Unstable Type 1 diabetes

7. Study Design

Primary Purpose

Device Feasibility

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

N-of-1 trials consists in a prospectively planned, multiple crossover study in a single individual.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Reference treatment (Open-Loop)

Arm Type

Active Comparator

Arm Description

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

Arm Title

DBLHU system (Closed-Loop)

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

Low Glucose Predictive Suspend system

Other Intervention Name(s)

Open-loop condition

Intervention Description

consists of sensor-augmented pump therapy (SAP) / Low Glucose Predictive Suspend system (with predictive low glucose management technology)

Intervention Type

Device

Intervention Name(s)

DBLHU System

Other Intervention Name(s)

Closed-loop condition

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Measured by continuous glucose monitoring

Time Frame

14 days for each treatment period

Secondary Outcome Measure Information:

Title

Evolution over time of the DBLHU system's performance on a day-to-day and determination of the optimization delay of glycemic control

Description

Measured by continuous glucose monitoring

Time Frame

Over twenty-four hour periods on the four weeks of each treatment period and of the 24-week and 48-week extented CL period.

Title

Percent of CGM time in glucose range 70-180 mg/dl during nighttime.

Description

Measured by continuous glucose monitoring

Time Frame

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.

Title

Percent of CGM time in glucose range 70-180 mg/dl during daytime.

Description

Measured by continuous glucose monitoring

Time Frame

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.

Title

Percent of CGM time with glucose < 70mg/dl, < 60mg/dl, < 54mg/dl and < 50mg/dl

Description

Measured by continuous glucose monitoring

Time Frame

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.

Title

Percent of CGM time with glucose > 180mg/dl, > 250mg/dl, > 300mg/dl and > 360mg/dl

Description

Measured by continuous glucose monitoring

Time Frame

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.

Title

Average glycemia level

Description

Measured by continuous glucose monitoring

Time Frame

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.

Title

Estimated HbA1c (eHbA1c) levels / glucose management indicator (GMI)

Description

Measured by continuous glucose monitoring

Time Frame

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.

Title

HbA1c levels

Description

Measured by blood sampling

Time Frame

HbA1c value at the week 24 and week 48 of extented CL period.

Title

Glucose coefficient of variation (CV) and Standard deviation (SD)

Description

Measured by continuous glucose monitoring

Time Frame

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.

Title

Rate of CGM excursions below 54 mg/dl (3.0 mM) for at least 15 min

Description

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

Time Frame

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.

Title

Comparison of MAGE index and Low Blood Glucose Index (LBGI)

Description

Mean amplitude of glucose excursions and Low Glucose index as measured by continuous glucose monitoring

Time Frame

Over twenty-four hour periods on the third and fourth weeks of each treatment period and during 24-week extension period

Title

Number of acute metabolic events (severe hypoglycemia, severe Diabetic Ketoacidosis [DKA])

Description

Time Frame

During 4 weeks of each treatment period and during 24-week and 48-week extension period

Title

Number of severe hypoglycemia with loss of consciousness

Description

Number of severe hypoglycemia with loss of consciousness

Time Frame

During 4 weeks of each treatment period and during 24-week and 48-week extension period

Title

Number of hospitalizations for severe hypoglycemia or ketoacidosis

Description

Number of hospitalizations

Time Frame

During 4 weeks of each treatment period and during 24-week and 48-week extension period

Title

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

Description

DTSQ satisfaction questionnaire, with scale from 6 to 0 where 0 is the worth and 6 the best outcome.

Time Frame

after baseline period (2-week); after crossover period; after 24-week and after 48-week extension period

Title

Percentage of CGM time in glucose range 70-180 mg/dl, during 24 hours periods

Description

Measured by continuous glucose monitoring

Time Frame

24-week and 48-week extension period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

22 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pierre Yves BENHAMOU, Pr

Organizational Affiliation

University Hospital, Grenoble

Official's Role

Principal Investigator

Facility Information:

Facility Name

Grenoble Alpes University Hospital

City

Grenoble

ZIP/Postal Code

38700

Country

France

Facility Name

Lille University Hospital

City

Lille

ZIP/Postal Code

59037

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Diabeloop for Highly Unstable Type 1 Diabetes

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