Closed-loop Control of Glucose Levels (Artificial Pancreas) for 24 Hours in Adults With Type 2 Diabetes Under Intensive Insulin Therapy

An Open-label, Randomized, Two-way, Cross-over Multicenter Study to Assess the Efficacy of Closed-loop Strategy as Compared to Multiple Daily Injections in Regulating Glucose Levels During 24 Hours in Adults With Type 2 Diabetes Under Intensive Insulin Therapy

The introduction of insulin pump therapy in patients with type 2 diabetes using multiple daily injections and poorly controlled can be considered in order to improve glycemic control. Recent developments of continuous glucose sensors and insulin infusion pumps have motivated the research toward "closed-loop'' strategies to regulate glucose levels for patients with diabetes. In a closed-loop strategy, the pump(s) infusion rate is altered based on a computer generated recommendation that rely on continuous glucose sensor readings. This study confirmed the feasibility and potential of the closed-loop strategy to improve glycemic control while reducing the risk of hypoglycemia in patients with type 2 diabetes but did not target the population most likely to benefit from this strategy.The objective ot this study is to compare the efficacy of closed-loop strategy to multiple daily injections in regulating glucose levels for 24 hours in elderly adults with type 2 diabetes under intensive insulin therapy. The investigators hypothesize that closed-loop strategy will increase the time spent in the target range in adults with type 2 diabetes compared to multiple daily injections.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Other: 24-hour intervention with multiple daily injections; Drug: Insulin; Device: Dexcom G4 Platinum; Other: 24-hour intervention with closed-loop strategy; Device: Insulin pump Accu-Chek Combo

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1R7
      • Institut de recherches cliniques de Montreal
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Type 2 diabetes.
2. Males and females ≥ 55 years of old.
3. Body mass index above 25 kg/m2
4. Non fragile defined based on Moorhouse et al. scale [23].
5. Using at least 3 insulin injections per day. However, basal insulin injection must be injected at bedtime without injection of basal insulin in the morning. Combination with any other anti-diabetic therapy is acceptable as long at this therapy was introduced at least 6 weeks prior the 1s intervention and is kept stable all along the protocol.
6. HbA1c above 6%.

Exclusion Criteria:

1. Advanced

   1. Nephropathy defined by creatinine clearance <30 ml/min.
   2. Retinopathy as proliferative retinopathy or recent (<3 month) eye bleeding or laser therapy. If the patient have undergone panphoto-coagulation inclusion is acceptable.
   3. Autonomic neuropathy with clinically significant gastroparesis according to investigator evaluation.
2. Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
3. A recent (< 2 months) injury to body or limb, muscular disorder, use of any medication or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the ability to walk.
4. A recent (< 2 months) infection needing IV antibiotic or hospitalization
5. Severe hypoglycemic episode within two weeks of screening.
6. Current use of glucocorticoid medication (by any route of administration except low dose stable inhaled).
7. Recent initiation or dose modification (<2 months) of therapy known to interfere with glucose metabolism (e.g. neuroleptics, anti-psychotics, etc.)
8. Known or suspected allergy to the trial products or meal contents.
9. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Multiple daily injections; Subjects will use multiple daily injections to regulate glucose levels. Subject's usual insulin analog will be used.	Other: 24-hour intervention with multiple daily injections; Subjects will be admitted at the research clinical facility at 20:00. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. The subjects will carry on with their normal insulin therapy. Two periods of walking of 15 minutes will be performed at 10:00 and 15:00. Meals will be served at 8:00, 12:00 and 17:00. The CHO content of meals will be adapted to subject's usual CHO intake. Venous blood samples (4 ml each) will be obtained for the measurement of the plasma glucose and insulin. Plasma glucagon and C-peptide will be measured every hour. Blood samples will be drawn every 20 minutes.; Drug: Insulin; Subject's usual insulin analog will be used.; Device: Dexcom G4 Platinum; In both visits, glucose levels will be measure with the Dexcom G4 Platinum (Dexcom)
Active Comparator: Closed-loop strategy; Variable subcutaneous insulin infusion rates will be used to regulate glucose levels. Subject's usual fast-acting insulin analog will be infused using a subcutaneous infusion pumps (Accu-Chek Combo, Roche). The glucose level as measured by the real time sensor (Dexcom G4 Platinum, Dexcom) will be entered manually into the computer every 10 minutes. The pumps' infusion rate will then be changed manually based on the computer generated recommendation infusion rates.	Drug: Insulin; Subject's usual insulin analog will be used.; Device: Dexcom G4 Platinum; In both visits, glucose levels will be measure with the Dexcom G4 Platinum (Dexcom); Other: 24-hour intervention with closed-loop strategy; Subjects will be admitted at the research clinical facility at 20:00. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. A cartridge containing subject's usual fast acting insulin analog will be placed in the insulin pump. Closed-loop strategy will start at 21:00 until 21:00 the next day. Neither basal nor prandial insulin injections will be given. Two periods of walking of 15 minutes will be performed at 10:00 and 15:00. Meals will be served at 8:00, 12:00 and 17:00. The CHO content of meals will be adapted to subject's usual CHO intake. Venous blood samples (4 ml each) will be obtained for the measurement of the plasma glucose and insulin. Plasma glucagon and C-peptide will be measured every hour. Blood samples will be drawn every 20 minutes.; Device: Insulin pump Accu-Chek Combo; During closed-loop intervention, the Accu-Chek Combo (Roche) insulin pump will be used

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time of plasma glucose concentrations spent in the target range	The target range is defined as between 4.0 and 10.0 mmol/L 2-hour postprandial and between 4.0 to 8.0 mmol/L otherwise.	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Total insulin delivery	24 hours
Percentage of time of plasma glucose levels spent between 4.0 to 10.0 mmol/L	24 hours
Percentage of time of plasma glucose levels spent below 4.0 mmol/L	24 hours
Percentage of time of plasma glucose levels spent below 3.5 mmol/L	24 hours
Percentage of time of plasma glucose levels spent above 8.0 mmol/L	24 hours
Percentage of time of plasma glucose levels spent above 10.0 mmol/L	24 hours
Percentage of time of overnight plasma glucose levels spent below 4.0 mmol/L	8 hours
Percentage of time of overnight plasma glucose levels spent between 4.0 and 8.0 mmol/L	8 hours
Percentage of time of overnight plasma glucose levels spent between 4.0 and 10.0 mmol/L	8 hours
Percentage of time of overnight plasma glucose levels spent below 3.5 mmol/L	8 hours
Percentage of time of overnight plasma glucose levels above 8.0 mmol/L	8 hours
Percentage of time of overnight plasma glucose levels above 10.0 mmol/L	8 hours
Area under the curve of plasma glucose levels below 4.0 mmol/L	24 hours
Area under the curve of plasma glucose levels below 3.5 mmol/L	24 hours
Area under the curve of plasma glucose levels above 8.0 mmol/L	24 hours
Area under the curve of plasma glucose levels above 10.0 mmol/L	24 hours
Area under the curve of overnight plasma glucose levels below 4.0 mmol/L	8 hours
Area under the curve of overnight plasma glucose levels below 3.5 mmol/L	8 hours
Area under the curve of overnight plasma glucose levels above 8.0 mmol/L	8 hours
Area under the curve of overnight plasma glucose levels above 10.0 mmol/L	8 hours
Mean glucose levels	24 hours
Standard deviation of plasma glucose concentrations	24 hours
Coefficient of variance of plasma glucose concentrations	24 hours
Number of patients experiencing at least one hypoglycemic event requiring treatment	24 hours
Number of patients experiencing at least one hypoglycemic event requiring treatment	8 hours

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal
• Collaborators: Réseau de recherche en santé cardiométabolique, diabète et obésité

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: July 1, 2015
• First Submitted That Met QC Criteria: July 2, 2015
• First Posted (Estimate): July 3, 2015

Study Record Updates

• Last Update Posted (Actual): June 11, 2019
• Last Update Submitted That Met QC Criteria: June 7, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Elderly; Insulin; Hypoglycemia; Type 2 diabetes; Artificial pancreas; Closed-loop strategy; Multiple daily injections
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: CLASS-12