Safety of Overestimation of a Meal Insulin Bolus in the Context of Dual-hormone Closed-loop Operation

NCT02626936 | Completed Phase 2

• 1 other identifier: CLASS Safety meal study
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

In previous studies, investigators have studied if a pre-meal insulin bolus based on estimated carbohydrate meal size would alleviate the burden of carbohydrate counting without a significant degradation in postprandial glucose control. With this strategy, the patient would only have to evaluate the size of the meal in terms of carbohydrate (snack, regular, large or very large) It is however important to establish safety of this simplified meal bolus approach. The safety of overestimating a meal insulin bolus in the context of single and dual-hormone CLS with the simplified meal strategy needs to be determined. Computer simulation will be used to get a reasonable estimate of risks related to over-estimation with single-hormone closed-loop while over-estimation with dual-hormone closed-loop will be tested in adults with type 1 diabètes Investigators hypothesize that dual-hormone closed-loop with overestimated meal size bolus will not increase time below 4.0 mmol/L compared to dual-hormone closed-loop with an adequately estimated meal size bolus

Conditions

Type 1 Diabetes

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of time below 4.0 mmol/L

  The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.

Secondary Outcomes (11)

• Mean glucose

  The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.

• Percentage of time of glucose concentrations between 4.0 and 8.0 mmol/L

  The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.

• Percentage of time of glucose concentrations between 4.0 and 10.0 mmol/L

  The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.

• Percentage of time of glucose concentrations below 3.1 mmol/L

  The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.

• Area under the curve of glucose values below 4.0 mmol/L

  The outcome measure will be calculated over the 4 hours following the breakfast meal given on the dual-hormone closed-loop intervention. The 4-hour period is from 9:00 to 13:00.

Study Arms (2)

Dual-hormone CL with overestimation of meal size category

ACTIVE COMPARATOR

A large size standardized meal of 75g of carbohydrates will be provided to the patient and the meal size will be overestimated by one category, which will result in a meal insulin bolus for a meal of 95g of carbohydrates.

Other: Dual-hormone closed-loop; Drug: Insulin; Drug: Glucagon; Device: Dexcom G4 Platinum glucose sensor; Device: Accu Chek Combo insulin pump

Dual-hormone CL with adequate estimation of meal size category

ACTIVE COMPARATOR

A large size standardized meal of 75g of carbohydrates will be provided to the patient and the meal size will be adequately estimated, which will result in a meal insulin bolus for a meal of 65g of carbohydrates.

Other: Dual-hormone closed-loop; Drug: Insulin; Drug: Glucagon; Device: Dexcom G4 Platinum glucose sensor; Device: Accu Chek Combo insulin pump

Interventions

Dual-hormone closed-loop OTHER

Interventions will be undertaken one to 5 days after sensor insertion. Subjects will be admitted at the research center at 7:00 am. Subject's pump will be substituted with the study pump and an additional pump containing glucagon will be installed. At 7:00, CLS will be initiated. At 9:00, a standardized breakfast (75g CHO) will be served. Study subjects will consume the same meal on the two intervention days. During the intervention, patients will be allowed to do sedentary activities. Patients will allowed to consume caffeine during the intervention, but will have to replicate their caffeine consumption on both interventions.The intervention day will end at 13:00.

Dual-hormone CL with adequate estimation of meal size category; Dual-hormone CL with overestimation of meal size category

Insulin DRUG

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

Dual-hormone CL with adequate estimation of meal size category; Dual-hormone CL with overestimation of meal size category

Glucagon DRUG

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

Dual-hormone CL with adequate estimation of meal size category; Dual-hormone CL with overestimation of meal size category

Dexcom G4 Platinum glucose sensor DEVICE

Dual-hormone CL with adequate estimation of meal size category; Dual-hormone CL with overestimation of meal size category

Accu Chek Combo insulin pump DEVICE

Dual-hormone CL with adequate estimation of meal size category; Dual-hormone CL with overestimation of meal size category

Eligibility Criteria

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

You may qualify if:

• Males and females ≥ 18 years 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 and currently using a fast actin insulin analog (Lispro, Aspart or Guilisine).
• Last (less than 3 months) HbA1c ≤ 10%.
• Currently using carbohydrate counting as the meal insulin dose strategy.

You may not qualify if:

• Clinically significant microvascular complications: nephropathy (estimated glomerular filtration rate below 40 ml/min), neuropathy (especially diagnosed gastroparesis) or severe proliferative retinopathy as judged by the investigator.
• Recent (\< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
• Pregnancy.
• Severe hypoglycemic episode within 1 month of screening.
• Agents affecting gastric emptying (Motilium®, Prandase®, Victoza®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, SGLT-2 inhibitors and DPP-4 inhibitors) if not at a stable dose for 3 months. Otherwise, these medications are acceptable and will be kept stable during the entire protocol.
• Oral steroids unless patients present a low stable dose (e.g. 10 mg or less of prednisone per day or physiological doses, less than 35 mg/day, of hydrocortisone Cortef®). Inhale steroids at stable dose in the last month are acceptable.
• Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator (e.g. unstable psychiatric condition).
• Failure to comply with team's recommendations (e.g. not willing to change pump parameters, follow algorithm's suggestions, etc).

Sponsors & Collaborators

• Institut de Recherches Cliniques de Montreal: lead

Study Sites (1)

Institut de recherches cliniques de Montréal

Montreal, Quebec, H2W 1R7, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Insulin Resistance

Interventions

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)

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: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 3, 2015
• First Posted: December 10, 2015
• Study Start: January 1, 2016
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: June 10, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)