Closed-loop Control of Postprandial Glucose Levels After Meals With Different Macronutrients Content in Adults With Type 1 Diabetes

An Open-label, Randomized, Four-way, Cross-over Study to Examine the Efficacy of Single-hormone Closed-loop System in Regulating Glucose Levels in Adults With Type 1 Diabetes Following Meals of Various Macronutrient Contents: a Pilot Study

Carbohydrates are the main determinant of post-meal glucose excursion. However, fat and protein have been shown to also impact the postprandial glucose control, adding to the complexity of meal insulin calculation. Few studies have looked at the effect of macronutrients other than carbohydrates on postprandial glucose excursions with the closed-loop strategy. The objective of this study is to test whether the single-hormone closed-loop strategy can achieve similar post-meal glucose control with meals with a fixed carbohydrate content, but high in protein and/or fat when compared to a meal with a fixed carbohydrate content only.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: Patient's insulin pump; Drug: Insulin; Device: Dexcom G4 Platinum glucose sensor; Other: Single-hormone closed-loop

• 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 fast-acting insulin analog (Lispro, Aspart or Guilisine).
4. Last (less than 3 months) HbA1c ≤ 10%.

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. Ongoing pregnancy.
4. Severe hypoglycemic episode within 1 month of screening.
5. Agents affecting gastric emptying (Motilium®, Prandase®, all GLP-1 analogs) 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®). Inhaled 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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Carbohydrate meal	Device: Patient's insulin pump; The patient's insulin pump will be used to regulate glucose levels.; Drug: Insulin; Patient's usual fast-acting insulin analog will be used.; Device: Dexcom G4 Platinum glucose sensor; The Dexcom G4 Platinum glucose sensor will be used to measure glucose levels.; Other: Single-hormone closed-loop; Interventions will be undertaken 1 to 5 days after sensor insertion. Subjects will be admitted at IRCM at 6:30 am in a fasting state. At 7:00, single-hormone closed-loop will be initiated. At 8:00, if glucose levels are between 3.5 and 12.5 mmol/L, the meal will be served. Patients will have 20 minutes to consume the meal. If glucose levels are not in this target range, the meal will be delayed for a maximum of 45 minutes. If after 45 minutes, glucoses levels are still not between 3.5 and 12.5 mmol/L, the test will be cancelled and rescheduled. The test meals will be: 1) 75g of CHO; 2) 75g of CHO + 35g of protein; 3) 75g of CHO + 35g of fat; or 4) 75g of CHO + 35g of protein + 35g of fat. The intervention day will end at 13:00.
Active Comparator: Carbohydrate + fat meal	Device: Patient's insulin pump; The patient's insulin pump will be used to regulate glucose levels.; Drug: Insulin; Patient's usual fast-acting insulin analog will be used.; Device: Dexcom G4 Platinum glucose sensor; The Dexcom G4 Platinum glucose sensor will be used to measure glucose levels.; Other: Single-hormone closed-loop; Interventions will be undertaken 1 to 5 days after sensor insertion. Subjects will be admitted at IRCM at 6:30 am in a fasting state. At 7:00, single-hormone closed-loop will be initiated. At 8:00, if glucose levels are between 3.5 and 12.5 mmol/L, the meal will be served. Patients will have 20 minutes to consume the meal. If glucose levels are not in this target range, the meal will be delayed for a maximum of 45 minutes. If after 45 minutes, glucoses levels are still not between 3.5 and 12.5 mmol/L, the test will be cancelled and rescheduled. The test meals will be: 1) 75g of CHO; 2) 75g of CHO + 35g of protein; 3) 75g of CHO + 35g of fat; or 4) 75g of CHO + 35g of protein + 35g of fat. The intervention day will end at 13:00.
Active Comparator: Carbohydrate + protein meal	Device: Patient's insulin pump; The patient's insulin pump will be used to regulate glucose levels.; Drug: Insulin; Patient's usual fast-acting insulin analog will be used.; Device: Dexcom G4 Platinum glucose sensor; The Dexcom G4 Platinum glucose sensor will be used to measure glucose levels.; Other: Single-hormone closed-loop; Interventions will be undertaken 1 to 5 days after sensor insertion. Subjects will be admitted at IRCM at 6:30 am in a fasting state. At 7:00, single-hormone closed-loop will be initiated. At 8:00, if glucose levels are between 3.5 and 12.5 mmol/L, the meal will be served. Patients will have 20 minutes to consume the meal. If glucose levels are not in this target range, the meal will be delayed for a maximum of 45 minutes. If after 45 minutes, glucoses levels are still not between 3.5 and 12.5 mmol/L, the test will be cancelled and rescheduled. The test meals will be: 1) 75g of CHO; 2) 75g of CHO + 35g of protein; 3) 75g of CHO + 35g of fat; or 4) 75g of CHO + 35g of protein + 35g of fat. The intervention day will end at 13:00.
Active Comparator: Carbohydrate + fat + protein meal	Device: Patient's insulin pump; The patient's insulin pump will be used to regulate glucose levels.; Drug: Insulin; Patient's usual fast-acting insulin analog will be used.; Device: Dexcom G4 Platinum glucose sensor; The Dexcom G4 Platinum glucose sensor will be used to measure glucose levels.; Other: Single-hormone closed-loop; Interventions will be undertaken 1 to 5 days after sensor insertion. Subjects will be admitted at IRCM at 6:30 am in a fasting state. At 7:00, single-hormone closed-loop will be initiated. At 8:00, if glucose levels are between 3.5 and 12.5 mmol/L, the meal will be served. Patients will have 20 minutes to consume the meal. If glucose levels are not in this target range, the meal will be delayed for a maximum of 45 minutes. If after 45 minutes, glucoses levels are still not between 3.5 and 12.5 mmol/L, the test will be cancelled and rescheduled. The test meals will be: 1) 75g of CHO; 2) 75g of CHO + 35g of protein; 3) 75g of CHO + 35g of fat; or 4) 75g of CHO + 35g of protein + 35g of fat. The intervention day will end at 13:00.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the curve of sensor glucose levels	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean sensor glucose levels	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.
Peak glucose excursion	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.
Time to peak glucose	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.
Percentage of time of sensor glucose concentrations between 3.9 and 7.8 mmol/L	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.
Percentage of time of sensor glucose concentrations between 3.9 and 10 mmol/L	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.
Percentage of time of sensor glucose concentrations above 10 mmol/L	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.
Percentage of time of sensor glucose concentrations above 13.9 mmol/L	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.
Total insulin delivery	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.
Standard deviation of glucose levels	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.
Coefficient of variation of glucose levels	The outcome measure will be calculated over the 5 hours following the breakfast meal given on the single-hormone closed-loop intervention. The 5-hour period is from 8:00 to 13:00.

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: May 13, 2016
• First Submitted That Met QC Criteria: May 13, 2016
• First Posted (Estimate): May 17, 2016

Study Record Updates

• Last Update Posted (Actual): October 30, 2017
• Last Update Submitted That Met QC Criteria: October 26, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Glucose control; Meal; Artificial pancreas; Closed-loop system
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Insulin; Insulin, Globin Zinc; Hormones
• Other Study ID Numbers: CLASS-Macro

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO