Clinical trial NCT05133765: The SMART B Exercise Study :''The SMART Study''
Official title: Optimising Glycaemia Around Dynamic Physical Exercise With Advanced Hybrid-closed-loop Therapy Use in Type 1 Diabetes: ''The SMART Study''
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypoglycemia
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: Swansea University
First posted: 2021-11-24
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Three period randomised cross-over clinical trial
Primary purpose: TREATMENT

Brief summary: Despite the established health benefits conveyed by physical activity for people with type 1 diabetes (T1D), participation rates remain low, with fear of hypoglycaemia, lack of freedom to engage in unplanned activities, and uncertainty in making appropriate adjustments to insulin and nutritional therapy reported as the leading barriers to regular exercise engagement. Indeed, the synergistic glucose lowering effects of peripheral hyperinsulinaemia and exercising muscle tissue accentuate the risk of exercise-related hypoglycaemia for individuals with T1D, particularly if performed post-prandially. Hence, the introduction of commercially available artificial pancreas systems, also known as ''advanced hybrid-closed-loop'' (AHCL) systems, that regulate insulin rates with minimal user interaction constitute compelling therapeutic aids with clinically relevant potential. Nevertheless, we know little about their safe and efficacious integration around dynamic physical exercise. Nor do we know how alterations in carbohydrate fueling strategies around exercise effect subsequent glucose trends.

This study aims to 1) compare the efficacy of an AHCL system versus usual care insulin pump therapy, with carbohydrates taken before or during exercise, in optimising TIR around dynamic physical exercise and 2) explore the influence of carbohydrate intake before versus during exercise on the metabolomic, hormonal and physiological responses to exercise.

Detailed description: Following successful completion of a screening visit, participants will attend the laboratory to complete 3 experimental visits during which they will undertake a 45-minute bout of moderate intensity continuous exercise on a bicycle ergometer at \~60% of the individualised VȮ2max. Prior to commencing exercise, participants will consume a standardised low-glycaemic index, carbohydrate-based meal (equating to 0.75g.CHO.kg.bm-1) with, or without, a 25% reduction in their meal-time insulin dose as well as with carbohydrates before or during exercise (according to the randomisation). Venous blood glucose sampling will be taken in 15-minute intervals leading into and after exercise with 5-minute intervals performed during exercise. Samples will be used to retrospectively cross-compare the metabolic, hormonal, and physiological responses between visits. Visits 1 \& 2 will be separated by ≥14 days to ensure adequate familiarisation with the AHCL system whilst visits 2 \& 3 will be separated by ≥3days. Each participant will undertake 1 screening and 3 experimental visits equating to a total of 80 study visits.

Eligibility criteria: Inclusion Criteria:

* • Type 1 diabetes ≥2 years.

  * HbA1c;

    * 58-63 mmol/mol (maximum 30% of participants) OR
    * ≥ 64 mmol/mol (minimum 70% of participants)
  * Insulin pump treatment ≥12 months
  * CGM or isCGM use ≥6 months
  * Novorapid use ≥4 weeks
  * Carbohydrate counting and use of the insulin pump bolus calculator for most snacks and meals.
  * Carbohydrate intake \>80 grams per day (assessed by review of intake recorded in the insulin pump during the 2 weeks prior to the screening visit)

Exclusion Criteria:

* • Breast-feeding, pregnancy or planning to become pregnant.

  * Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to study start.
  * Use of hybrid closed-loop systems
  * Daily use of paracetamol (acetaminophen)
  * Alcohol or drug abuse.
  * Severe cardiac disease or retinopathy contraindicating HbA1c \<53 mmol/mol.
  * Other concomitant medical or psychological condition that according to the investigator's assessment makes the person unsuitable for study participation.
  * Lack of compliance with key study procedures at the discretion of the investigator.
  * Unacceptable adverse events at the discretion of the investigator

Primary outcomes:
measure: Comparison of TIR in blood glucose values during, and 1-hour after, dynamic physical exercise
timeFrame: 0 minutes to +105 minutes
Secondary outcomes:
measure: To compare the influence of carbohydrate feeding before versus during exercise on the physiological responses to dynamic physical exercise
timeFrame: 0 minutes to +45 minutes
Other outcomes:
measure: Comparison of the maximum BG concentration
timeFrame: -90 minutes to +105 minutes
measure: Comparison of the minimum BG concentration
timeFrame: -90 minutes to +105 minutes
measure: Comparison of standard deviation in BG concentrations
timeFrame: -90 min to +105 minutes
measure: Comparison of mean BG concentrations
timeFrame: -90 minutes to +105 minutes
measure: Comparison of the depth of BG hypoglycaemic events
timeFrame: -90 minutes to +105 minutes
measure: Comparison of the occurrence of BG hypoglycaemic events
timeFrame: -90 minutes to +105 minutes
measure: ΔBGexercise: Comparison of the changes in BG during exercise
timeFrame: 0 minutes to +45 minutes
measure: ΔiGexercise: Comparison of the changes in iG during exercise
timeFrame: 0 minutes to +45 minutes
measure: ΔiGfeeding: Comparison of the changes in iG after feeding
timeFrame: -90 minutes to 0 minutes
measure: Comparison of TBR level 2 in iG values
timeFrame: -90 minutes to +105 minutes
measure: Comparison of TBR level 1 in iG values
timeFrame: -90 minutes to +105 minutes
measure: Comparison of TAR level 1 in iG values
timeFrame: -90 minutes to +105 minutes
measure: Comparison of TAR level 2 in iG values
timeFrame: -90 minutes to +105 minutes
measure: Comparison of mean iG concentrations
timeFrame: -90 minutes to +105 minutes
measure: Comparison of the standard deviation in iG concentrations
timeFrame: -90 minutes to +105 minutes
measure: Comparison of the coefficient of variation in iG concentrations
timeFrame: -90 minutes to +105 minutes
measure: Comparison of the minimum iG concentration
timeFrame: -90 minutes to +105 minutes
measure: Comparison of the maximum iG concentration
timeFrame: -90 minutes to +105 minutes
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
References: