The SMART B Exercise Study :''The SMART Study''

Study Overview
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Brief Summary
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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
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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.

Official Title
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Optimising Glycaemia Around Dynamic Physical Exercise With Advanced Hybrid-closed-loop Therapy Use in Type 1 Diabetes: ''The SMART Study''

Conditions
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Hypoglycemia

Intervention / Treatment
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* Device: Insulin pump


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Three period randomised cross-over clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SMART B1 - Usual care insulin pump<br>Usual care pump therapy arm with carbohydrate consumption before exercise | Device: Insulin pump<br>* Alterations in insulin pump therapy or carbohydrate consumption<br>|
| Experimental: SMART B2 - Advanced hybrid closed loop insulin pump with carbohydrates before exercise<br>Advanced hybrid closed loop therapy arm with carbohydrate consumption before exercise | Device: Insulin pump<br>* Alterations in insulin pump therapy or carbohydrate consumption<br>|
| Experimental: SMART B3 - Advanced hybrid closed loop insulin pump with carbohydrates during exercise<br>Advanced hybrid closed loop therapy arm with carbohydrate consumption during exercise | Device: Insulin pump<br>* Alterations in insulin pump therapy or carbohydrate consumption<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of TIR in blood glucose values during, and 1-hour after, dynamic physical exercise | Comparison of the amount of time spent with blood glucose values within the target range during, and 1-hour after, dynamic physical exercise | 0 minutes to +105 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the influence of carbohydrate feeding before versus during exercise on the physiological responses to dynamic physical exercise | To compare the influence of carbohydrate feeding before versus during exercise on the physiological responses to dynamic physical exercise | 0 minutes to +45 minutes |