Assessment of the Efficacy of the Artificial Pancreas Combined With a Qualitative Meal Size Estimation to Control Postprandial Glucose Levels

NCT04031599 | Completed DMC

• 1 other identifier: CLASS18
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

Postprandial glycemic excursions are major determinants of overall glycemic control in type 1 diabetes. Carbohydrate content of ingested meals is the main determinant of post-meal glucose excursion. Accurate carbohydrate counting is a critical aspect of managing postprandial blood glucose levels. accurate carbohydrate counting is considered by patients as a significant burden and frustrating task. The closed-loop system (CLS) is composed of three components: glucose sensor to read glucose levels, insulin pump to infuse insulin and a dosing mathematical algorithm to decide on the required insulin dosages based on the sensor's readings. The objective of this study is to compare the efficacy of two strategies to regulate glucose levels in outpatient settings in adults with type 1 diabetes: 1) single-hormone CLS with rapid acting insulin analogue combined with carbohydrate counting; 2) single-hormone CLS with rapid acting insulin analogue combined with simplified qualitative meal-size estimation. A sub-study will also be proposed to participants. Postprandial exercise combines two situations complicating CLS operation: a high plasma insulin due to insulin on-board related to meal boluses and rapid blood glucose changes (postprandial blood glucose excursion and then drop during exercise) making input from the glucose sensor less accurate. The objective of this sub-study will be to explore the safety and efficacy of the CLS using the combined strategy of pre-meal exercise announcement and meal bolus reduction of 33% when exercise is performed 1 hour compared to 2 hours post meal time.

Conditions

Type 1 Diabetes

Keywords

Type 1 diabetes; Artificial pancreas; Closed-loop system; Insulin; Postprandial glucose; Exercise

Outcome Measures

Primary Outcomes (2)

• Percentage of time of glucose levels spent between 3.9 and 10.0 mmol/L

  504 hours

• Relative decrease in glucose levels during exercise compared to pre-breakfast levels (sub-study)

  Difference between pre-breakfast levels and the lowest glucose level from the start of the exercise until the end of exercise

  3.5 or 4.5 hours

Secondary Outcomes (51)

• Percentage of time of glucose levels spent between 3.9 and 7.8 mmol/L

  504 hours

• Percentage of time of glucose levels spent below 3.9 mmol/L

  504 hours

• Percentage of time of glucose levels spent below 3.3 mmol/L

  504 hours

• Percentage of time of glucose levels spent below 2.8 mmol/L

  504 hours

• Percentage of time of glucose levels spent above 10.0 mmol/L

  504 hours

Study Arms (2)

Carbohydrate counting

ACTIVE COMPARATOR

Rapid acting insulin analogue with carbohydrate counting

Device: Single-hormone closed-loop system; Device: Insulin pump; Device: Continuous glucose monitoring system; Drug: Aspart or Lispro; Other: Carbohydrate counting; Other: 3-week intervention; Other: 1-hour postprandial exercise (sub-study); Other: 2-hour postprandial exercise (sub-study); Other: Exercise announcement and meal bolus reduction (sub-study)

Simplified qualitative meal size estimation

ACTIVE COMPARATOR

Rapid acting insulin analogue with simplified qualitative meal size estimation

Device: Single-hormone closed-loop system; Device: Insulin pump; Device: Continuous glucose monitoring system; Drug: Aspart or Lispro; Other: Simplified qualitative meal-size estimation strategy; Other: 3-week intervention

Interventions

Single-hormone closed-loop system DEVICE

Every 10 minutes, the glucose levels as measured by the sensor will be transferred automatically to a LG Google Nexus Smartphone that the algorithm is running on, which will calculate the recommended doses and will send them wirelessly to the infusion pump.

Carbohydrate counting; Simplified qualitative meal size estimation

Insulin pump DEVICE

Tandem Diabetes Care

Carbohydrate counting; Simplified qualitative meal size estimation

Continuous glucose monitoring system DEVICE

Dexcom G6

Carbohydrate counting; Simplified qualitative meal size estimation

Aspart or Lispro DRUG

Aspart or lispro will be infused with the infusion pump

Carbohydrate counting; Simplified qualitative meal size estimation

Carbohydrate counting OTHER

Participants will be required to enter an estimate of the carbohydrate content of their meal into the phone. Insulin boluses will be calculated based on grams of carbohydrates and participant's insulin-to-carbohydrate ratio. Carbohydrate-matching full prandial bolus will be given 5 to 10 minutes before the meal.

Carbohydrate counting

Simplified qualitative meal-size estimation strategy OTHER

A pre-meal partial prandial bolus will be given 5-10 minutes before the meal. The partial bolus will be based on the estimated meal size (small, regular, large and extra-large). The closed-loop system will give the remaining insulin needed based on the sensor readings. For this strategy, meal size will be defined as: small as any meal less than 30g, regular meal as any meal between 30g and 60g CHO, large meal as any meal between 60g and 90g CHO, extra-large meal for anything above 90g CHO.

Simplified qualitative meal size estimation

3-week intervention OTHER

Glucose levels will be regulated by the single-hormone closed-loop system for 3 consecutive weeks.

Carbohydrate counting; Simplified qualitative meal size estimation

1-hour postprandial exercise (sub-study) OTHER

60 minute exercise will be started one hour after the meal time.

Carbohydrate counting

2-hour postprandial exercise (sub-study) OTHER

60 minute exercise will be started two hours after meal time

Carbohydrate counting

Exercise announcement and meal bolus reduction (sub-study) OTHER

Meal bolus reduction of 33% at meal time and exercise announcement (increased target glucose from 6 to 9mmolL) to the CLS algorithm

Carbohydrate counting

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 of old.
• Clinical diagnosis of type 1 diabetes for at least one year. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
• The subject will have been on insulin pump therapy for at least 3 months.
• Currently using, or willing to switch to Lispro U100 or Aspart for the duration of the study.
• HbA1c \< 10%.

You may not qualify if:

• Clinically significant nephropathy, neuropathy (e.g. known or suspected gastroparesis) or retinopathy (e.g. proliferative retinopathy) as judged by the investigator
• Recent (\< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery
• Anticipated need to use acetaminophen during interventions with the closed-loop system
• Pregnancy (ongoing or current attempt to become pregnant)
• Breastfeeding
• No nearby third party for assistance if needed (e.g. severe hypoglycemia glucagon treatment)
• Plans to go abroad or travel at more than 3 hours distance from Montreal during the trial period
• Severe hypoglycemic episode within two weeks of screening or during the run-in period
• Severe hyperglycemic episode requiring hospitalization in the last 3 months
• Current use of glucocorticoid medication (except low stable dose and inhaled steroids)
• Agents affecting gastric emptying (Motilium®, Victoza®, Ozempic®, Trulicity®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, Prandase®, 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.
• Current use of SGLT-2 inhibitors unless at a stable dose for at least 3 months and appropriate ketone testing performed.
• Known or suspected allergy to the trial products
• Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator
• Anticipation of a significant change in exercise regimen between admission and end of the trial (i.e. starting or stopping an organized sport)

Sponsors & Collaborators

• Institut de Recherches Cliniques de Montreal: lead

Study Sites (2)

Montreal Clinical Research Institute

Montreal, Quebec, H2W 1R7, Canada

Location

McGill University Health Center

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (1)

• Myette-Cote E, Molveau J, Wu Z, Raffray M, Devaux M, Tagougui S, Rabasa-Lhoret R. A Randomized Crossover Pilot Study Evaluating Glucose Control During Exercise Initiated 1 or 2 h After a Meal in Adults with Type 1 Diabetes Treated with an Automated Insulin Delivery System. Diabetes Technol Ther. 2023 Feb;25(2):122-130. doi: 10.1089/dia.2022.0338. Epub 2022 Dec 6.

  PMID: 36399114 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance; Motor Activity

Interventions

Insulin Infusion Systems; Continuous Glucose Monitoring; Insulin Aspart; Insulin Lispro; Methods

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Delivery Systems; Drug Therapy; Therapeutics; Infusion Pumps; Equipment and Supplies; Artificial Organs; Surgical Equipment; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; Investigative Techniques; Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Rémi Rabasa-Lhoret

  Montreal Clinical Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor

Study Record Dates

• First Submitted: July 22, 2019
• First Posted: July 24, 2019
• Study Start: July 10, 2020
• Primary Completion: November 27, 2021
• Study Completion: December 14, 2021
• Last Updated: January 28, 2022

Record last verified: 2022-01

Locations

CA (2)