The Effects of Different Exercise Modalities in Adolescents With Type 1 Diabetes Using AID Systems (MODE2022)

Objective:

The overall objective of this study is to assess the efficacy of the current recommended guidelines for physical activity (PA) in response to acute moderate intensity continous exercise (MICE) and high intensity interval exercise (HIIE) among adolescents with type 1 diabetes (T1D) using automated insulin delivery (AID) systems (MiniMed 780G and Tandem Control-IQ).

Methods:

This study will be a two-period, cross-over, clinical trial with between and within cohort comparisons of two different exercise modalities among a total of 24 age-, sex-, and insulin-dose-matched adolescents with T1D (12 using MiniMed 780G and 12 using Tandem Control-IQ).

Endpoint:

The primary endpoint is sensor-derived time in range (3.9 mmol/L-10.0 mmol/L) around exercise

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Behavioral: High Intensity Interval Exercise; Behavioral: Moderate Intensity Continous Exercise

Detailed Description

Participants included in the study will perform a cardiopulmonary exercise testing (CPET) before the exercise study visits, to prescribe subsequent exercise intensity thresholds. Participants will have a canula placed in a antecubital vein for plasma sampling during the test.

Participants will undertake two exercise visits each including a bout of exercise on a stationary bicycle of either one of two exercise modalities; i.) high-intensity interval exercise with sprints at ~85% of VO2max (HIIE); ii.) moderate intensity continuous exercise at ~60% of VO2max (MICE).

Participants will arrive at the research facility, Steno Diabetes Center Copenhagen, in the afternoon. As per the current recommended guidelines, the MICE-session will be announced to the AID systems 60 minutes in advance, whereas the HIIE-session will not be announced. Participants will have a canula placed in a antecubital vein for plasma sampling.

Participants will rest for 60 minutes, exercise for 45 minutes and rest again for 75 minutes before leaving the research facility. During exercise participants will be fitted with a spirometry face mask to compute ventilatory thresholds and indirect calorimetry (Vyaire Vyntus® CPX, Intramedic A/S) and a telemetry chest strap (Polar H10) for integrated HR heart rate (HR) measurements with the spirometry device.

In the MICE session: After 15 minutes post-exercise rest the temporary target/exercise mode is turned off.

Around each study visit (24 hours prior until 24 hours after), sensor glucose as well as sleep and physical activity will be recorded. Sensor glucose will be measured by participants' own devices. Sleep and physical activity level will be assessed with a wrist-worn accelerometer, ActiGraph wGT3X-BT (ActiGraph, Pensacola, FL).

Study days will be separated by at least three days.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emilie Lindkvist, MD; Phone Number: +45 20187762; Email: emilie.lindkvist@regionh.dk
• Study Contact Backup: Name: Kirsten Nørgaard; Email: kirsten.noergaard@regionh.dk

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Recruiting
    • Steno Diabetes Center Copenhagen
    • Contact: Emilie B Lindkvist; Phone Number: +4520187762; Email: emilie.lindkvist@regionh.dk
    • Contact: Jannet Svensson; Email: jannet.svensson.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 13 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 13-17 years old
• Type 1 diabetes > 1 year
• Use of Tandem t:slim X2 Control-IQ or Medtronic MiniMed 780G with connected continous glucose monitor > 3 months
• HbA1c below 75 mmol/L

Exclusion Criteria:

• Use of anti-diabetic medicine other than insulin
• Breastfeeding, pregnancy or planning to become pregnant
• Lack of compliance with key study procedures at the discretion of the investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High Intensity Interval Exercise; Plasma and sensor glucose is monitored before, during and after a bout of high intensity interval exercise	Behavioral: High Intensity Interval Exercise; High Intensity Interval Exercise: 5 minutes resting phase @ 0 watts.; 5-minute warm up phase @ 20 watts.; 40 minutes of interval work consisting of eight bouts of 1-minute cycling at a power output corresponding to ~85% of VO2max interspersed with 4-minute recovery periods at 20 watts.; 5 minutes resting phase @ 0 watts.
Active Comparator: Moderate Intensity Continous Exercise; Plasma and sensor glucose is monitored before, during and after a bout of moderate intensity continous exercise	Behavioral: Moderate Intensity Continous Exercise; Moderate Intensity Continous Exercise: 5 minutes resting phase @ 0 watts.; 5-minute warm up phase @ 20 watts.; 40 minutes of MICE 65% VO2max.; 5 minutes resting phase @ 0 watts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time spent in sensor-derived time in range (3.9-10.0 mmol/L) during and after a bout of exercise	Percentage	T = 0 to T = +120 (120 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of hypo- (<3.9 mmol/L) and hyperglycemic (>10.0 mmol/L) occurrences during exercise session as measured by sensor and plasma sampling	Number	T = 0 to T = +45 (45 minutes)
Percentage of time spent below (<3.9 mmol/L), in (3.9-10.0 mmol/L) and above (>10.0 mmol/L) range during in-clinic phase, measured by sensor and plasma sampling	Percentage	T= -60 minutes to T= +120 minutes (3 hours)
Percentage of time spent below (<3.9 mmol/L), in (3.9-10.0 mmol/L) and above (>10.0 mmol/L) range during home-phase, measured by glucose sensor	Percentage	24 hours
Glycemic variability as coefficient of variation, measured by sensor during in-clinic phase	Percentage	T= -60 minutes to T= +120 minutes (3 hours)
Glycemic variability as coefficient of variation, measured by plasma sampling during in-clinic phase	Percentage	T= -60 minutes to T= +120 minutes (3 hours)
Glycemic variability as standard deviation, measured by sensor during in-clinic phase	mmol/L	T= -60 minutes to T= +120 minutes (3 hours)
Glycemic variability as standard deviation, measured by plasma sampling during in-clinic phase	mmol/L	T= -60 minutes to T= +120 minutes (3 hours)
Glycemic variability as coefficient of variation measured by glucose sensor during home-phase	Percentage	24 hours
Glycemic variability as standard deviation measured by glucose sensor during home-phase	Mmol/L	24 hours
Number of rescue glucose interventions to treat hypoglycemia (<3.9 mmol/L) during in-clinic and home-phase	Number	27 hours
Area Under the Curve and absolute concentration of serum total insulin during in-clinic phase	Units	T= -60 minutes to T= +120 minutes (3 hours)
Dynamics of plasma glucoregulatory hormone responses during in-clinic phase	Change in concentration	T= -60 minutes to T= +120 minutes (3 hours)
Dynamics of plasma metabolites during in-clinic phase	Change in concentration	T= -60 minutes to T= +120 minutes (3 hours)
Glucose changes during exercise (delta change expressed as absolute [mmol/L]) during in-clinic phase	mmol/L	T= -60 minutes to T= +120 minutes (3 hours)
Glucose changes during exercise (delta change relativized as a rate of change [mmol/min]) during in-clinic phase	mmol/min	T= -60 minutes to T= +120 minutes (3 hours)
Amount of correction boluses given by each automated insulin delivery system during activation of temporary target and exercise mode	Number	T= -60 minutes to T= +60 minutes (2 hours)
Comparison of heart rate (HR) during high intensity interval exercise and moderate intensity continous exercise session	Beats pr minute	T = 0 to T = +45 (45 minutes)
Comparison of respiratory exchange ratio (RER) during high intensity interval exercise and moderate intensity continous exercise session	Ratio	T = 0 to T = +45 (45 minutes)
Comparison of oxygen consumption (VO2) during high intensity interval exercise and moderate intensity continous exercise session	L/min	T = 0 to T = +45 (45 minutes)
Comparison of carbon dioxide output (VCO2) during high intensity interval exercise and moderate intensity continous exercise session	L/min	T = 0 to T = +45 (45 minutes)
Comparison of carbohydrate oxidation during high intensity interval exercise and moderate intensity continous exercise session	g/min	T = 0 to T = +45 (45 minutes)
Comparison of lipid oxidation during high intensity interval exercise and moderate intensity continous exercise session	g/min	T = 0 to T = +45 (45 minutes)
Comparison of resting metabolic rate after exercise session	kj/min	T =+45 to T=+120 (75 minutes)
Plasma lactate response before, during and after cardiopulmonary exercise testing	mmol/L	30 minutes
Plasma glucose response before, during and after cardiopulmonary exercise testing	mmol/L	30 minutes
Respiratory exchange ratio (RER) collected continuously during cardiopulmonary exercise testing visit	L/min	30 minutes
Oxygen consumption (VO2) collected continuously during cardiopulmonary exercise testing visit	L/min	30 minutes
Carbon dioxide output (VCO2) collected continuously during cardiopulmonary exercise testing visit	L/min	30 minutes
Sleep efficiency assessed by Actigraph GT3x the night before study visits compared to after study visits.	Percentage	Night 1-2
Wake time after sleep onset assessed by Actigraph GT3x the night before study visits compared to after study visits	Mins	Night 1- 2
Energy expenditure assessed by Actigraph GT3x.	Kcal	Day 1-3
Physical activity level assessed by Actigraph GT3x	sedentary, light or moderate-to-vigorous	Day1-3

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Investigators: Principal Investigator: Emilie Lindkvist, MD, Steno Diabetes Center Copenhagen, Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2022
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: October 5, 2022
• First Submitted That Met QC Criteria: November 8, 2022
• First Posted (Actual): November 16, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: November 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
• Other Study ID Numbers: MODE2022

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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