Clinical trial NCT04089462: Effects of Frequency and Duration of Exercise in People With Type 1 Diabetes A Randomized Crossover Study
Official title: Effects of Frequency and Duration of Exercise in People With Type 1 Diabetes - A Randomized Crossover Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Insulin Hypoglycemia
Keywords: Exercise
Insulin pump
Diabetes Mellitus, Type 1
Guidelines
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
First posted: 2019-09-13
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: An open-labelled randomized controlled crossover study will be performed. The participants will go through the following elements:

1. Screening day
2. Run-in period
3. Intervention period
4. Wash-out period
5. Intervention period
Primary purpose: TREATMENT

Brief summary: According to the Standards of Medical Care in Diabetes by the American Diabetes Association, people with diabetes should aim for 30 minutes of moderate-to-vigorous intensity aerobic exercise at least 5 days a week or a total of 150 minutes per week and doing some type of strength training at least 2 times per week in addition to aerobic activity. However, the effects of different forms and intervals of exercise on glycemic control are not well established. Exercise increases the risk of hypoglycemia both during and several hours after exercise.

There are several strategies to avoid hypoglycemia during exercise. The most common strategy is to reduce insulin and to take carbohydrates before the exercise starts. Short-acting insulin analogs have a duration of approximately four hours, thus reductions need to be planned and done well in advance before the exercise starts. Since different types of exercise (aerobic, strength training or high intensity training) affect blood glucose in different ways and most exercise sessions include a combination of the types, these strategies are often associated with difficulties in obtaining stable blood glucose. The American Diabetes Association guidelines do not explicitly recommend a daily workout routine but outline recommendations for weekly amounts of exercise as there is currently insufficient evidence on the ideal timing, frequency and duration of exercise for preventing hypoglycemia.

Hypothesis: in people with type 1 diabetes, time in hypoglycemia can be reduced if exercise is performed daily over five consecutive days compared to the same total amount of exercise performed at 2 days with at least 2 days interval.

Aim: to evaluate the impact of the same total amount of exercise split into either five consecutive sessions or two sessions with at least 2 days in between on percentage of time spent in hypoglycemia and other glycemic parameters in people with type 1 diabetes.

Detailed description: The participants will go through two interventions: Exercise one session per day for five consecutive days and Exercise one session per day for two days within five days. The exercise session will start with anaerobic (push-ups, back-curls, sit-ups, triceps-dips and jumps) exercise followed by aerobic exercise (moderate intensity of running, walking or cycling). Between the two intervention periods, there will be a wash-out period.

Intervention: 'Exercise one session per day for five consecutive days'. Duration per session: Anaerobic: 4 min, Aerobic: 30 min. Sessions per intervention period: Five. Total duration per intervention period: Anaerobic: 20 min. Aerobic: 150 min. Total: 170 min

Intervention:Exercise one session per day for two days within five days. Duration per session: Anaerobe: 10 min, Aerobe: 75 min. Sessions per intervention period: 2. Total duration per intervention period: Anaerob: 20 min Aerobe: 150 min Total: 170 min

Eligibility criteria: Inclusion Criteria:

* Type 1 Diabetes ≥ 2 year
* Insulin pump ≥ 1 year.
* Use of carbohydrate counting and the insulin pump bolus calculator for all meals

Exclusion Criteria:

* Use of anti-diabetic medicine (other than insulin), per oral or injected corticosteroids or other drugs affecting glucose metabolism during the intervention period or within 30 days prior to study start
* Known or suspected alcohol or drug abuse
* Other concomitant medical or psychological condition that according to the investigator's assessment makes the participant unsuitable for study participation
* Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods
* Inability to understand the participants' information and to give informed consent
* Chronic use or unable to stop acetaminophen (paracetamol) use
* Allergy to the patch of CGM
* Hypoglycemia unawareness, quantified by Pedersen-Bjergaard
* Severe hypoglycemia within the last year
* Vigorous-intensity exercise for more than 60 minutes on 3 days or more per week

Primary outcomes:
measure: Percentage of time spent in the hypoglycemic range (CGM <3.9 mmol/l)
timeFrame: The primary intervention period from 06:00h study day 1 - 06:00h study day 6 (ITT)
Secondary outcomes:
measure: Percentage of time spent in the hypoglycemic range (CGM <3.9 mmol/l)
timeFrame: Primary intervention period from 06:00h study day 1 - 06:00h study day 6 PP
measure: Percentage of time spent in the alert and clinical hypoglycemic range
timeFrame: Study day 1: The day when the first exercise session is performed and registered.
measure: Percentage of time spent in the alert and clinical hypoglycemic range
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Percentage of time spent in the alert and clinical hypoglycemic range
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Percentage of time spent in the alert and clinical hypoglycemic range
timeFrame: Day time: 06:00-22:00h from during study day 1 to study day 6.
measure: Percentage of time spent in the alert and clinical hypoglycemic range
timeFrame: Night time: 22:00-06:00h from during study day 1 to study day 6.
measure: Percentage of time spent in the alert and clinical hypoglycemic range
timeFrame: The time the participant has recorded start and end of exercise session during study day 1 to study day 6
measure: Number of alert and clinical hypoglycemia events
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Number of alert and clinical hypoglycemia events
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Number of alert and clinical hypoglycemia events
timeFrame: Day time: 06:00-22:00h during study day 1 - study day 6
measure: Number of alert and clinical hypoglycemia events
timeFrame: Night time: 22:00-06:00h during study day 1 - study day 6
measure: Number of alert and clinical hypoglycemia events
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 study day 6
measure: Number of severe hypoglycemia events during
timeFrame: Study day 1: The day when the first exercise session is performed and registered
measure: Number of severe hypoglycemia events
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Number of severe hypoglycemia events
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Number of severe hypoglycemia events
timeFrame: Day time: 06:00-22:00h during study day 1 - study day 6
measure: Number of severe hypoglycemia events
timeFrame: Night time: 22:00-06:00h during study day 1 - study day 6
measure: Number of severe hypoglycemia events
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 - study day 6
measure: Percentage of time in range (3.9-10 mmol/l)
timeFrame: Study day 1: The day when the first exercise session is performed and registered
measure: Percentage of time in range (3.9-10 mmol/l)
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Percentage of time in range (3.9-10 mmol/l)
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Percentage of time in range (3.9-10 mmol/l)
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Percentage of time in range (3.9-10 mmol/l)
timeFrame: Night time: 22:00-06:00h during study day 1 -study day 6
measure: Percentage of time in range (3.9-10 mmol/l)
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Percentage of time in good range (3.9-7.8 mmol/l)
timeFrame: Study day 1: The day when the first exercise session is performed and registered.
measure: Percentage of time in good range (3.9-7.8 mmol/l)
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Percentage of time in good range (3.9-7.8 mmol/l)
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Percentage of time in good range (3.9-7.8 mmol/l)
timeFrame: Day time: 06:00-22:00h and Night time: 22:00-06:00h during study day 1-study day 6
measure: Percentage of time in good range (3.9-7.8 mmol/l)
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1-study day 6
measure: Percentage of time in hyperglycemia (>10 mmol/l)
timeFrame: Study day 1: The day when the first exercise session is performed and registered.
measure: Percentage of time in hyperglycemia (>10 mmol/l)
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Percentage of time in hyperglycemia (>10 mmol/l)
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Percentage of time in hyperglycemia (>10 mmol/l)
timeFrame: Night time: 22:00-06:00h during study day 1 -study day 6
measure: Percentage of time in hyperglycemia (>10 mmol/l)
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1-study day 6
measure: Percentage of time in hyperglycemia (>10 mmol/l) during all the predefined time blocks. Per protocol analysis and intention-to-treat analysis
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Glycemic variability measured as standard deviation (SD), coefficient of variation (CV) and low and high blood glucose index (LBGI/HBGI) during all the predefined time blocks in the intervention period
timeFrame: Study day 1: The day when the first exercise session is performed and registered.
measure: Glycemic variability measured as standard deviation (SD), coefficient of variation (CV) and low and high blood glucose index (LBGI/HBGI) during all the predefined time blocks in the intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Glycemic variability measured as standard deviation (SD), coefficient of variation (CV) and low and high blood glucose index (LBGI/HBGI) during all the predefined time blocks in the intervention period
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Glycemic variability measured as standard deviation (SD), coefficient of variation (CV) and low and high blood glucose index (LBGI/HBGI) during all the predefined time blocks in the intervention period
timeFrame: Night time: 22:00-06:00h during study day 1 -study day 6
measure: Glycemic variability measured as standard deviation (SD), coefficient of variation (CV) and low and high blood glucose index (LBGI/HBGI) during all the predefined time blocks in the intervention period
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Mean CGM glucose level du during all the predefined time blocks in the intervention period
timeFrame: Study day 1: The day when the first exercise session is performed and registered.
measure: Mean CGM glucose level du during all the predefined time blocks in the intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Mean CGM glucose level du during all the predefined time blocks in the intervention period
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Mean CGM glucose level du during all the predefined time blocks in the intervention period
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Mean CGM glucose level du during all the predefined time blocks in the intervention period
timeFrame: Night time: 22:00-06:00h during study day 1 -study day 6
measure: Mean CGM glucose level du during all the predefined time blocks in the intervention period
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: CGM estimated eA1c during the primary intervention period
timeFrame: The Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Total carbohydrate intake registered from the insulin pumps during all the predefined time blocks in the intervention period
timeFrame: Study day 1: The day when the first exercise session is performed and registered.
measure: Total carbohydrate intake registered from the insulin pumps during all the predefined time blocks in the intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Total carbohydrate intake registered from the insulin pumps during all the predefined time blocks in the intervention period
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Total carbohydrate intake registered from the insulin pumps during all the predefined time blocks in the intervention period
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Total carbohydrate intake registered from the insulin pumps during all the predefined time blocks in the intervention period
timeFrame: Night time: 22:00-06:00h during study day 1 -study day 6
measure: Total carbohydrate intake registered from the insulin pumps during all the predefined time blocks in the intervention period
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Carbohydrate interventions for prevention and treatment of hypoglycemia registered by the participants in the booklet for the primary and total intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Carbohydrate interventions for prevention and treatment of hypoglycemia registered by the participants in the booklet for the primary and total intervention period
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days)
measure: Change in total daily insulin dose (basal and bolus insulin) of 7 days prior to screening day and during the primary and total intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Change in total daily insulin dose (basal and bolus insulin) of 7 days prior to screening day and during the primary and total intervention period
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Actigraph wrist wear time during all predefined time blocks
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Actigraph wrist wear time during all predefined time blocks
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Actigraph wrist wear time during all predefined time blocks
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Actigraph wrist wear time during all predefined time blocks
timeFrame: Night time: 22:00-06:00h during study day 1 -study day 6
measure: Actigraph wrist wear time during all predefined time blocks
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Physical activity energy expenditure (accelerometer and heart rate based) measured as kcal during all predefined time blocks
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Physical activity energy expenditure (accelerometer and heart rate based) measured as kcal during all predefined time blocks
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Physical activity energy expenditure (accelerometer and heart rate based) measured as kcal during all predefined time blocks
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Physical activity energy expenditure (accelerometer and heart rate based) measured as kcal during all predefined time blocks
timeFrame: Night time: 22:00-06:00h during study day 1 -study day 6
measure: Physical activity energy expenditure (accelerometer and heart rate based) measured as kcal during all predefined time blocks
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Metabolic expenditure rate for the primary intervention periods
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Metabolic expenditure rate for the primary intervention periods
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Number of exercise (light to vigorous) and sedentary bouts in the primary intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Number of exercise (light to vigorous) and sedentary bouts in the primary intervention period
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days)
measure: Time in sedentary during predefined time blocks
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Time in sedentary during predefined time blocks
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Time in sedentary during predefined time blocks
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Time in sedentary during predefined time blocks
timeFrame: Night time: 22:00-06:00h during study day 1 -study day 6
measure: Time in sedentary during predefined time blocks
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Time in light physical activity during predefined time blocks
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Time in light physical activity during predefined time blocks
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Time in light physical activity during predefined time blocks
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Time in light physical activity during predefined time blocks
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Time in moderate physical activity during predefined time blocks
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Time in moderate physical activity during predefined time blocks
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days).
measure: Time in moderate physical activity during predefined time blocks
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Time in moderate physical activity during predefined time blocks
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Time in vigorous physical activity during predefined time blocks
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Time in vigorous physical activity during predefined time blocks
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days)
measure: Time in vigorous physical activity during predefined time blocks
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Time in vigorous physical activity during predefined time blocks
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Number of steps during predefined time blocks
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Number of steps during predefined time blocks
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days)
measure: Number of steps during predefined time blocks
timeFrame: Day time: 06:00-22:00h during study day 1-study day 6
measure: Number of steps during predefined time blocks
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Heart rate during exercise sessions
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: R-R intervals during exercise sessions (f)
timeFrame: Exercise time: The time the participant has recorded start and end of exercise session during study day 1 -study day 6
measure: Sleep latency (min) during the primary and total intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Sleep latency (min) during the primary and total intervention period
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days)
measure: Total sleep time (min) during the primary and total intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Total sleep time (min) during the primary and total intervention period
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days)
measure: Sleep efficiency (%) during the primary and total intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Sleep efficiency (%) during the primary and total intervention period
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days)
measure: Number of awakening during sleep in the primary and total intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Number of awakening during sleep in the primary and total intervention period
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days)
measure: Time of awakening during sleep in the primary and total intervention period
timeFrame: Primary intervention period: 06:00h study day 1 - 06:00h study day 6 (= 5 x 24-hour days)
measure: Time of awakening during sleep in the primary and total intervention period
timeFrame: Secondary intervention period: 08:00h day 1 - 08:00h day 8 (= 7 x 24-hour days)
measure: Question about patient preference regarding the two study arms
timeFrame: At the end of study. Study day 6 the last interventions period.
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Isabelle IK Steineck, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Steineck IIK, Ranjan AG, Schmidt S, Norgaard K. Time spent in hypoglycemia is comparable when the same amount of exercise is performed 5 or 2 days weekly: a randomized crossover study in people with type 1 diabetes. BMJ Open Diabetes Res Care. 2021 Jan;9(1):e001919. doi: 10.1136/bmjdrc-2020-001919.