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

NCT02846857 | Withdrawn Phase 2 DMC

• 1 other identifier: CLASS-17
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Type 1 Diabetes

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of time of glucose levels below 3.9 mmol/L

  15 weeks

Secondary Outcomes (21)

• HbA1c

  15 weeks

• Percentage of time of glucose levels spent in the target range

  15 weeks

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

  15 weeks

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

  15 weeks

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

  15 weeks

Study Arms (3)

Sensor-augmented pump therapy

ACTIVE COMPARATOR

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.

Other: 15-week intervention with sensor-augmented pump; Device: Insulin pump; Device: Continuous glucose monitoring system; Drug: Insulin

Single-hormone closed-loop strategy

ACTIVE COMPARATOR

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.

Other: 15-week intervention with single-hormone closed-loop; Device: Insulin pump; Device: Continuous glucose monitoring system; Drug: Insulin

Dual-hormone closed-loop strategy

ACTIVE COMPARATOR

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.

Other: 15-week intervention with dual-hormone closed-loop; Device: Insulin pump; Device: Continuous glucose monitoring system; Drug: Insulin; Drug: Glucagon

Interventions

15-week intervention with sensor-augmented pump OTHER

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.

Sensor-augmented pump therapy

15-week intervention with single-hormone closed-loop OTHER

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.

Single-hormone closed-loop strategy

15-week intervention with dual-hormone closed-loop OTHER

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. Participants will have to reconstitute glucagon everyday.

Dual-hormone closed-loop strategy

Insulin pump DEVICE

MiniMed® Paradigm® Veo™, Medtronic

Dual-hormone closed-loop strategy; Sensor-augmented pump therapy; Single-hormone closed-loop strategy

Continuous glucose monitoring system DEVICE

Enlite sensor®, Medtronic

Dual-hormone closed-loop strategy; Sensor-augmented pump therapy; Single-hormone closed-loop strategy

Insulin DRUG

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

Dual-hormone closed-loop strategy; Sensor-augmented pump therapy; Single-hormone closed-loop strategy

Glucagon DRUG

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

Dual-hormone closed-loop strategy

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut de Recherches Cliniques de Montreal: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Insulin Resistance

Interventions

Methods; Insulin Infusion Systems; Continuous Glucose Monitoring; Insulin; Glucagon

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Investigative Techniques; Drug Delivery Systems; Drug Therapy; Therapeutics; Infusion Pumps; Equipment and Supplies; Artificial Organs; Surgical Equipment; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Proglucagon

Study Officials

• Rémi Rabasa-Lhoret

  Institut de recherches cliniques de Montréal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 25, 2016
• First Posted: July 27, 2016
• Primary Completion: July 22, 2019
• Last Updated: July 23, 2019

Record last verified: 2019-07