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

Type 1 Diabetes Clinical Trial

Official title:

A Single-blind, Randomized, Two-way, Cross-over Study to Examine the Safety of Overestimation of a Meal Insulin Bolus in the Context of Dual-hormone Closed-loop Operation Combined With a Simplified Qualitative Meal-size Estimation in Adults With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02626936
• Other study ID #: CLASS Safety meal study
• Status: Completed
• Phase: Phase 2
• First received: December 3, 2015
• Last updated: June 9, 2016
• Start date: January 2016
• Est. completion date: June 2016

Study information

• Verified date: June 2016
• Source: Institut de Recherches Cliniques de Montreal
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males and females = 18 years old.

2. Clinical diagnosis of type 1 diabetes for at least one year.

3. 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).

4. Last (less than 3 months) HbA1c = 10%.

5. Currently using carbohydrate counting as the meal insulin dose strategy.

Exclusion Criteria:

1. 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.

2. Recent (< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.

3. Pregnancy.

4. Severe hypoglycemic episode within 1 month of screening.

5. 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.

6. 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.

7. 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).

8. Failure to comply with team's recommendations (e.g. not willing to change pump parameters, follow algorithm's suggestions, etc).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Other:
• Dual-hormone closed-loop
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.

Drug:
• Insulin
Participant's usual fast-acting insulin analog will be used: Lispro (Humalog), Aspart (NovoRapid) or Glulisine (Apidra)
• Glucagon
Glucagon (Eli Lilly) will be used during dual-hormone closed-loop strategy.

Device:
• Dexcom G4 Platinum glucose sensor

• Accu Chek Combo insulin pump

Locations

Country	Name	City	State
Canada	Institut de recherches cliniques de Montréal	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Institut de Recherches Cliniques de Montreal

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	Area under the curve of glucose values 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.	No
Secondary	Number of patients with at least one hypoglycemic event with or without symptoms		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.	No
Secondary	Total number of hypoglycemic event 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.	No
Secondary	Total carbohydrate intake for hypoglycemia correction		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.	No
Secondary	Total insulin delivery		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.	No
Secondary	Total glucagon delivery		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.	No