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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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The Effects of Different Exercise Modalities in Adolescents With Type 1 Diabetes Using AID Systems

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Behavioral: High Intensity Interval Exercise
* Behavioral: Moderate Intensity Continous Exercise


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A two-period, cross-over, clinical trial with between and within cohort comparisons of two different exercise modalities in adolescents with type 1 diabetes
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High Intensity Interval Exercise<br>Plasma and sensor glucose is monitored before, during and after a bout of high intensity interval exercise | Behavioral: High Intensity Interval Exercise<br>* 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.<br>|
| Active Comparator: Moderate Intensity Continous Exercise<br>Plasma and sensor glucose is monitored before, during and after a bout of moderate intensity continous exercise | Behavioral: Moderate Intensity Continous Exercise<br>* 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.<br>|

What is the study measuring?
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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 |