The SMART B Exercise Study :''The SMART Study'' (SMART)

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

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.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia
• Intervention / Treatment: Device: Insulin pump

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Gentofte, Denmark, 2820
    • Steno Diabetes Center Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the maximum BG concentration	Comparison of the maximum blood glucose concentration before, during and for 1 hour after physical exercise	-90 minutes to +105 minutes
Comparison of the minimum BG concentration	Comparison of the minimum blood glucose concentration before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
Comparison of standard deviation in BG concentrations	Comparison of standard deviation in blood glucose concentrations before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 min to +105 minutes
Comparison of mean BG concentrations	Comparison of mean blood glucose concentrations before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
Comparison of the depth of BG hypoglycaemic events	Comparison of the depth of blood glucose hypoglycaemic events before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
Comparison of the occurrence of BG hypoglycaemic events	Comparison of the occurrence of blood glucose hypoglycaemic events before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
ΔBGexercise: Comparison of the changes in BG during exercise	ΔBGexercise: Comparison of the changes in blood glucose during exercise before, during physical exercise (i.e., 0 min to +45min)	0 minutes to +45 minutes
ΔiGexercise: Comparison of the changes in iG during exercise	ΔiGexercise: Comparison of the changes in interstitial glucose during exercise during physical exercise (i.e., 0 min to +45min)	0 minutes to +45 minutes
ΔiGfeeding: Comparison of the changes in iG after feeding	ΔiGfeeding: Comparison of the changes in interstitial glucose after feeding before physical exercise (i.e., -90 min to 0 min)	-90 minutes to 0 minutes
Comparison of TBR level 2 in iG values	Comparison of the amount of time spent with interstitial glucose values below the target range level 2 before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
Comparison of TBR level 1 in iG values	Comparison of the amount of time spent with interstitial glucose values below the target range level 1 before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
Comparison of TAR level 1 in iG values	Comparison of the amount of time spent with interstitial glucose values above the target range level 1 before, during and for 1 hour after physical exercise (i.e., -0 min to +105min)	-90 minutes to +105 minutes
Comparison of TAR level 2 in iG values	Comparison of the amount of time spent with interstitial glucose values after the target range level 2 before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
Comparison of mean iG concentrations	Comparison of mean interstitial glucose concentrations before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
Comparison of the standard deviation in iG concentrations	Comparison of the standard deviation in interstitial glucose concentrations before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
Comparison of the coefficient of variation in iG concentrations	Comparison of the coefficient of variation in interstitial glucose concentrations before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
Comparison of the minimum iG concentration	Comparison of the minimum interstitial glucose concentration before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes
Comparison of the maximum iG concentration	Comparison of the maximum interstitial glucose concentration before, during and for 1 hour after physical exercise (i.e., -90 min to +105min)	-90 minutes to +105 minutes

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Collaborators: Swansea University

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2021
• Primary Completion (Actual): October 7, 2022
• Study Completion (Actual): October 7, 2022

Study Registration Dates

• First Submitted: September 14, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): November 10, 2022
• Last Update Submitted That Met QC Criteria: November 8, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: SMART B

Drug and device information, study documents

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