Comparison of FiAsp and Aspart During Postprandial Exercise in Adults With Type 1 Diabetes

A Double-blind, Randomized, Cross-over Study to Compare the Impact of Rapid-acting Insulin Aspart and Faster Acting Aspart (FiAsp) on Glucose Excursion During Postprandial Exercise in Adults With Type 1 Diabetes

Hypoglycemia is the main barrier for physical activity practice of patients with type 1 diabetes (T1D). For postprandial exercise, anticipation with meal insulin bolus reduction is the recommended method to reduce exercise-associated hypoglycemic risk. The impact of faster acting Aspart (FiAsp) pharmacokinetic on hypoglycemic risk has not yet been explored. This study will explore two different timings for exercise onset.

Objective: To compare the impact of rapid-acting insulin Aspart and faster acting Aspart (FiAsp) on glucose reduction during exercise.

Design: This study is a randomized, four-way, crossover study to compare the efficacy of 1) rapid-acting insulin Aspart, and 2) FiAsp on glucose reduction during an exercise performed 60 minutes or 120 minutes after breakfast. The insulin used and the timing of the exercise will be randomized. This project will be conducted at Institut de recherches cliniques de Montréal (IRCM, Montreal, Canada).

Hypothesis: Faster acting Aspart (FiAsp) will be non-inferior to insulin Aspart for hypoglycemic risk.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin Aspart; Other: 60-minutes postprandial exercise; Other: 120-minutes postprandial exercise; Drug: Insulin FiAsp

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Roxane St-Amand; Phone Number: 514-987-5597; Email: roxane.st-amand@ircm.qc.ca

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H2W 1R7
      • Institut de Recherches Cliniques de Montreal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males and females ≥ 18 years of old.
2. Clinical diagnosis of type 1 diabetes for at least one year.
3. HbA1c ≤ 9.5%.
4. Patients using multiple daily injections with basal-bolus insulin regimen and insulin analogs (pre-meal: Aspart, Lispro, Guilisine or Fiasp; basal: Detemir, Glargine U100 & U300, Degludec U100).
5. Written informed consent given.

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. Anemia (Hb < 100g/L).
4. Ongoing pregnancy or breastfeeding.
5. Severe hypoglycemic episode within two weeks of screening.
6. Other serious medical illness likely to interfere with study participation or with the ability to complete the exercise periods by the judgment of the investigator (e.g. orthopedic limitation).
7. Ongoing treatment with CSII (Continuous Subcutaneous Insulin Infusion) "insulin pump therapy".
8. Participation to a clinical trial in the last 3 months prior to inclusion in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspart - 60-minutes postprandial exercise	Drug: Insulin Aspart; An insulin bolus of Aspart will be given 5 minutes before breakfast; Other: 60-minutes postprandial exercise; A 60-minute exercise at 60% of VO2 peak will be performed 60 minutes after breakfast
Active Comparator: Aspart - 120-minutes postprandial exercise	Drug: Insulin Aspart; An insulin bolus of Aspart will be given 5 minutes before breakfast; Other: 120-minutes postprandial exercise; A 60-minute exercise at 60% of VO2 peak will be performed 120 minutes after breakfast
Active Comparator: FiAsp - 60-minutes postprandial exercise	Other: 60-minutes postprandial exercise; A 60-minute exercise at 60% of VO2 peak will be performed 60 minutes after breakfast; Drug: Insulin FiAsp; An insulin bolus of FiAsp will be given 5 minutes before breakfast
Active Comparator: FiAsp - 120-minutes postprandial exercise	Other: 120-minutes postprandial exercise; A 60-minute exercise at 60% of VO2 peak will be performed 120 minutes after breakfast; Drug: Insulin FiAsp; An insulin bolus of FiAsp will be given 5 minutes before breakfast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in plasma glucose levels during exercise	Difference between glucose levels at the beginning of the exercise and the lowest glucose levels from the start of the exercise until the end of the exercise	60 minutes (exercise period)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of time of plasma glucose levels spent below 4 mmol/L	60 minutes (exercise period)
Decremental area under the curve of plasma glucose levels	60 minutes (exercise period)
Area under the curve of plasma glucose levels below 4 mmol/L	60 minutes (exercise period)
Number of patients with an exercise-induced hypoglycemia below 3.9 mmol/L	60 minutes (exercise period)
Number of patients with an exercise-induced hypoglycemia below 3.3 mmol/L	60 minutes (exercise period)
Number of patients requiring an oral treatment for hypoglycemia	60 minutes (exercise period)
Total number of hypoglycemia episodes requiring treatment	60 minutes (exercise period)
Percentage of time of plasma glucose levels spent above 10 mmol/L	60 minutes (exercise period)
Percentage of time of plasma glucose levels spent between 4 and 10 mmol/L	60 minutes (exercise period)
Mean time (minutes) to the first hypoglycemic event	60 minutes (exercise period)
Amount of carbohydrates needed to treat a hypoglycemic event	60 minutes (exercise period)
Change in oxyhemoglobin in the vastus lateralis	60 minutes (exercise period)
Changes in deoxyhemoglobin in the vastus lateralis	60 minutes (exercise period)
Changes in total hemoglobin in the vastus lateralis	60 minutes (exercise period)
Percentage of time of plasma glucose levels spent between 4 and 10 mmol/L	90 minutes after the end of exercise
Percentage of time of plasma glucose levels spent below 4 mmol/L	90 minutes after the end of exercise
Percentage of time of plasma glucose levels spent above 10 mmol/L	90 minutes after the end of exercise
Area under the curve of plasma glucose levels below 4 mmol/L	90 minutes after the end of exercise
Number of patients requiring an oral treatment for hypoglycemia	90 minutes after the end of exercise
Total number of hypoglycemia episodes requiring treatment	90 minutes after the end of exercise
Total amount of carbohydrates needed to treat hypoglycemic events	90 minutes after the end of exercise
Area under the curve of plasma glucose levels	4.5 hours (entire protocol period)
Total number of hypoglycemia episodes requiring treatment	4.5 hours (entire protocol period)
Total amount of carbohydrates needed to treat hypoglycemic events	4.5 hours (entire protocol period)

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal
• Investigators: Principal Investigator: Remi Rabasa-Lhoret, Institut de Recherches Cliniques de Montreal

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2019
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): March 30, 2023

Study Registration Dates

• First Submitted: September 4, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: March 1, 2022

More Information

Terms related to this study

• 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; Insulin; Insulin, Globin Zinc; Insulin Aspart
• Other Study ID Numbers: FiAsp-Exercise

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No