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Closed-loop Control of Glucose Levels (Artificial Pancreas) for 15 Weeks in Adolescents and Adults With Type 1 Diabetes

Primary Purpose

Type 1 Diabetes

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

15-week intervention with sensor-augmented pump

15-week intervention with single-hormone closed-loop

15-week intervention with dual-hormone closed-loop

Insulin pump

Continuous glucose monitoring system

Insulin

Glucagon

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring Closed-loop system, Artificial pancreas, Type 1 diabetes, Hypoglycemia, Insulin, Glucagon

Eligibility Criteria

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

Inclusion Criteria:

Males and females ≥ 12 years of old.
Clinical diagnosis of type 1 diabetes for at least one year.
The subject will have been on insulin pump therapy for at least 3 months.
HbA1c ≤ 11%.

Exclusion Criteria:

Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
History of pheochromocytoma or insulinoma (glucagon could induce a hormonal response of these tumors)
Beta-blockers at high dose based on investigator's evaluation of dosage interference with glucagon (glucagon can modify effect of beta-blockers, mostly evident at very high doses)
Chronic indometacin treatment (can prevent glucagon effect on liver thus its ability to raise glucose)
Chronic acetaminophen treatment (can interfere with glucose sensor measurements)
Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding)
Anticholinergic drug (risk of interaction)
Pregnancy.
Severe hypoglycemic episode within two weeks of screening.
Current use of glucocorticoid medication (except low stable dose and inhaled steroids).
Known or suspected allergy to the trial products
Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
Anticipating a significant change in exercise regimen between admissions (i.e. starting or stopping an organized sport).
Treatments that could interfere with glucagon

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Sensor-augmented pump therapy

Single-hormone closed-loop strategy

Dual-hormone closed-loop strategy

Arm Description

Participants will use sensor-augmented pump therapy with low-glucose suspend to regulate glucose levels. The low-glucose suspend feature available in the MiniMed® Paradigm® Veo™, Medtronic combined with the Enlite sensor® will be used. This feature allows for suspension of insulin delivery at a pre-set sensor glucose value for up to 2 hours.

Variable subcutaneous insulin infusion will be used to regulate glucose levels. Participant's usual fast-acting insulin analog will be infused using a subcutaneous infusion pump (MiniMed® Paradigm® Veo™, Medtronic). Every 10 minutes, the glucose levels as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pump.

Variable subcutaneous insulin and glucagon mini-boluses will be infused using two separate subcutaneous infusion pumps to regulate glucose levels (MiniMed® Paradigm® Veo™, Medtronic). Participant's usual fast-acting insulin analog and Glucagon (Eli Lilly) will be used. Every 10 minutes, the glucose level as measured by the sensor (Enlite sensor®, Medtronic) will be transferred automatically to a smartphone, that harbors the algorithm, that will calculate the recommended doses and will send it wirelessly to the infusion pumps. Newly reconstituted glucagon will be used every 24 hours.

Outcomes

Primary Outcome Measures

Percentage of time of glucose levels below 3.9 mmol/L

Secondary Outcome Measures

HbA1c

Percentage of time of glucose levels spent in the target range

Target range is defined to be between 4 and 10 mmol/L from 7:00 to 22:00 and between 4 and 7.8 mmol/L from 22:00 to 7:00

Area under the curve of glucose levels below 3.9 mmol/L

Area under the curve of glucose levels below 3.3 mmol/L

Area under the curve of glucose levels below 2.8 mmol/L

Percentage of time of glucose levels below 3.3 mmol/L

Percentage of time of glucose levels below 2.8 mmol/L

Total number of hypoglycemic events below 3.1 mmol/L

Percentage of time of glucose levels above 7.8 mmol/L

Percentage of time of glucose levels above 10.0 mmol/L

Mean glucose levels

Standard deviation of glucose levels

Coefficient of variation of glucose levels

Total daily dose of insulin

Total daily dose of glucagon

Percentage of time of closed-loop operation

Percentage of time of glucose sensor availability

Time between failures due to glucose sensor unavailability

Time between failures due to pump connectivity

Percentage of time when patients switched back to insulin pump therapy

Percentage of time when the closed-loop was automatically switched to insulin pump therapy

Full Information

NCT ID

NCT02846857

First Posted

July 25, 2016

Last Updated

July 22, 2019

Sponsor

Institut de Recherches Cliniques de Montreal

1. Study Identification

Unique Protocol Identification Number

NCT02846857

Brief Title

Closed-loop Control of Glucose Levels (Artificial Pancreas) for 15 Weeks in Adolescents and Adults With Type 1 Diabetes

Official Title

An Open-label, Randomized, Multicenter Study to Assess the Efficacy of Single-hormone Closed-loop Strategy, Dual-hormone Closed-loop Strategy and Sensor-augmented Pump Therapy in Regulating Glucose Levels for 15 Weeks in Free-living Outpatient Conditions in Adolescents and Adults With Type 1 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Withdrawn

Study Start Date

undefined (undefined)

Primary Completion Date

July 22, 2019 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Institut de Recherches Cliniques de Montreal

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Closed-loop strategy is composed of three components: glucose sensor to read glucose levels, insulin pump to infuse insulin and a dosing mathematical algorithm to decide on the required insulin dosages based on the sensor's readings. A dual-hormone closed loop strategy regulates glucose levels through the infusion of two hormones: insulin and glucagon. The objective of this study is to compare, in a randomized multicenter trial, the effectiveness of single-hormone closed-loop, dual-hormone closed-loop, and sensor-augmented pump therapy with low-glucose suspend in regulating day-and-night glucose levels in outpatient settings for 15 weeks in adolescents and adults. The investigators hypothesize that dual-hormone closed-loop will reduce time spent in hypoglycemia compared to single-hormone closed-loop, which in turn will be more effective than sensor-augmented pump therapy with low-glucose suspend.

6. Conditions and Keywords

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

Type 1 Diabetes

Keywords

Closed-loop system, Artificial pancreas, Type 1 diabetes, Hypoglycemia, Insulin, Glucagon

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sensor-augmented pump therapy

Arm Type

Active Comparator

Arm Description

Arm Title

Single-hormone closed-loop strategy

Arm Type

Active Comparator

Arm Description

Arm Title

Dual-hormone closed-loop strategy

Arm Type

Active Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

15-week intervention with sensor-augmented pump

Intervention Description

A sensor will be inserted on the day before the start of the intervention by the participant. The participant will also have to install the study insulin pump. Participants will be advised to continue with study intervention at home for the next 15 weeks. Participants will have been previously shown how to use the study insulin pump.

Intervention Type

Other

Intervention Name(s)

15-week intervention with single-hormone closed-loop

Intervention Description

A sensor will be inserted on the day before the start of the intervention by the participant. On the first day of the intervention, participants will be admitted to the clinical research facility anytime between 8:00 am and 11:30 am. Training on connection and disconnection of the system, meal boluses, etc. will be given. Only participants demonstrating competency on use of study devices will be allowed to continue to the home study phase. Participants will be advised to continue with study intervention at home for the next 15 weeks.

Intervention Type

Other

Intervention Name(s)

15-week intervention with dual-hormone closed-loop

Intervention Description

Intervention Type

Device

Intervention Name(s)

Insulin pump

Intervention Description

MiniMed® Paradigm® Veo™, Medtronic

Intervention Type

Device

Intervention Name(s)

Continuous glucose monitoring system

Intervention Description

Enlite sensor®, Medtronic

Intervention Type

Drug

Intervention Name(s)

Insulin

Intervention Description

Participant's usual fast-acting insulin analog will be used: Lispro (Humalog), Aspart (NovoRapid) or Glulisine (Apidra)

Intervention Type

Drug

Intervention Name(s)

Glucagon

Intervention Description

Glucagon (Eli Lilly) will be used during dual-hormone closed-loop strategy.

Primary Outcome Measure Information:

Title

Percentage of time of glucose levels below 3.9 mmol/L

Time Frame

15 weeks

Secondary Outcome Measure Information:

Title

HbA1c

Time Frame

15 weeks

Title

Percentage of time of glucose levels spent in the target range

Description

Target range is defined to be between 4 and 10 mmol/L from 7:00 to 22:00 and between 4 and 7.8 mmol/L from 22:00 to 7:00

Time Frame

15 weeks

Title

Area under the curve of glucose levels below 3.9 mmol/L

Time Frame

15 weeks

Title

Area under the curve of glucose levels below 3.3 mmol/L

Time Frame

15 weeks

Title

Area under the curve of glucose levels below 2.8 mmol/L

Time Frame

15 weeks

Title

Percentage of time of glucose levels below 3.3 mmol/L

Time Frame

15 weeks

Title

Percentage of time of glucose levels below 2.8 mmol/L

Time Frame

15 weeks

Title

Total number of hypoglycemic events below 3.1 mmol/L

Time Frame

15 weeks

Title

Percentage of time of glucose levels above 7.8 mmol/L

Time Frame

15 weeks

Title

Percentage of time of glucose levels above 10.0 mmol/L

Time Frame

15 weeks

Title

Mean glucose levels

Time Frame

15 weeks

Title

Standard deviation of glucose levels

Time Frame

15 weeks

Title

Coefficient of variation of glucose levels

Time Frame

15 weeks

Title

Total daily dose of insulin

Time Frame

24 hours

Title

Total daily dose of glucagon

Time Frame

24 hours

Title

Percentage of time of closed-loop operation

Time Frame

15 weeks

Title

Percentage of time of glucose sensor availability

Time Frame

15 weeks

Title

Time between failures due to glucose sensor unavailability

Time Frame

15 weeks

Title

Time between failures due to pump connectivity

Time Frame

15 weeks

Title

Percentage of time when patients switched back to insulin pump therapy

Time Frame

15 weeks

Title

Percentage of time when the closed-loop was automatically switched to insulin pump therapy

Time Frame

15 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males and females ≥ 12 years of old. Clinical diagnosis of type 1 diabetes for at least one year. The subject will have been on insulin pump therapy for at least 3 months. HbA1c ≤ 11%. Exclusion Criteria: Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator. Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery. History of pheochromocytoma or insulinoma (glucagon could induce a hormonal response of these tumors) Beta-blockers at high dose based on investigator's evaluation of dosage interference with glucagon (glucagon can modify effect of beta-blockers, mostly evident at very high doses) Chronic indometacin treatment (can prevent glucagon effect on liver thus its ability to raise glucose) Chronic acetaminophen treatment (can interfere with glucose sensor measurements) Warfarin chronic treatment if INR monitoring cannot be evaluated (can increase the risk of bleeding) Anticholinergic drug (risk of interaction) Pregnancy. Severe hypoglycemic episode within two weeks of screening. Current use of glucocorticoid medication (except low stable dose and inhaled steroids). Known or suspected allergy to the trial products Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator. Anticipating a significant change in exercise regimen between admissions (i.e. starting or stopping an organized sport). Treatments that could interfere with glucagon

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rémi Rabasa-Lhoret

Organizational Affiliation

Institut de recherches cliniques de Montréal

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Closed-loop Control of Glucose Levels (Artificial Pancreas) for 15 Weeks in Adolescents and Adults With Type 1 Diabetes

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