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

NCT02490085 | Completed Phase 2

• 1 other identifier: CLASS-12
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Type 2 Diabetes

Keywords

Type 2 diabetes; Closed-loop strategy; Artificial pancreas; Insulin; Elderly; Multiple daily injections; Hypoglycemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (25)

• 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

Study Arms (2)

Multiple daily injections

ACTIVE COMPARATOR

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; Drug: Insulin; Device: Dexcom G4 Platinum

Closed-loop strategy

ACTIVE COMPARATOR

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.

Other: 24-hour intervention with closed-loop strategy; Drug: Insulin; Device: Insulin pump Accu-Chek Combo; Device: Dexcom G4 Platinum

Interventions

24-hour intervention with multiple daily injections OTHER

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.

Multiple daily injections

24-hour intervention with closed-loop strategy OTHER

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.

Closed-loop strategy

Insulin DRUG

Subject's usual insulin analog will be used.

Closed-loop strategy; Multiple daily injections

Insulin pump Accu-Chek Combo DEVICE

During closed-loop intervention, the Accu-Chek Combo (Roche) insulin pump will be used

Closed-loop strategy

Dexcom G4 Platinum DEVICE

In both visits, glucose levels will be measure with the Dexcom G4 Platinum (Dexcom)

Closed-loop strategy; Multiple daily injections

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes.
• Males and females ≥ 55 years of old.
• Body mass index above 25 kg/m2
• Non fragile defined based on Moorhouse et al. scale \[23\].
• 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.
• HbA1c above 6%.

You may not qualify if:

• Advanced
• Nephropathy defined by creatinine clearance \<30 ml/min.
• Autonomic neuropathy with clinically significant gastroparesis according to investigator evaluation.
• Recent (\< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
• 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.
• A recent (\< 2 months) infection needing IV antibiotic or hospitalization
• Severe hypoglycemic episode within two weeks of screening.
• Current use of glucocorticoid medication (by any route of administration except low dose stable inhaled).
• Recent initiation or dose modification (\<2 months) of therapy known to interfere with glucose metabolism (e.g. neuroleptics, anti-psychotics, etc.)
• Known or suspected allergy to the trial products or meal contents.
• Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.

Sponsors & Collaborators

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

Study Sites (2)

Institut de recherches cliniques de Montréal

Montreal, Quebec, H2W 1R7, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance; Hypoglycemia

Interventions

Methods; Insulin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Investigative Techniques; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

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: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 1, 2015
• First Posted: July 3, 2015
• Study Start: October 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: June 11, 2019

Record last verified: 2019-06

Locations

CA (2)