Simplified Meal Approach Using Hybrid Closed-loop Insulin Delivery in Youth and Young Adults With Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of the study is to examine whether a simplified meal approach (as compared to exact carbohydrate counting) can alleviate the need of carbohydrate counting without worsening postprandial control in youth and young adults with type 1 diabetes using hybrid closed-loop insulin delivery with the Cambridge Artificial Pancreas FX System (CamAPS FX system).

Detailed Description
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Optimal glycaemic control is the aim of diabetes care and critical in the prevention of diabetes-related complications. Despite advances in diabetes technologies and medications, many current youth and young adults (YYA) with type 1 diabetes (T1D) are not meeting desired glycaemic targets, representing a missed opportunity for improving lifetime outcomes. A variety of factors including peer group influences, importance of body image, less parental oversight, greater risk-taking, and performance pressure challenge daily self-management in YYA with T1D. Disengagement from care and barriers for optimal glycaemic management in YYA have been mainly shown to be substantially influenced by perceived burden of daily tasks. Although the recently introduced closed-loop systems, which link insulin delivery to sensor glucose levels, offer promising opportunities to improve glucose control in YYA with T1D, they still require the user to estimate carbohydrates. The perceived burden of exact carbohydrate counting (ECC), the limited evidence supporting its glycaemic benefit and corrective potential of algorithm-driven background insulin titration question its necessity during hybrid-closed loop insulin treatment. Instead, a simplified meal approach (SMA), which only requires the user to select the meal carbohydrate category (small/medium/large), has the potential to alleviate the burden of ECC during hybrid closed-loop insulin therapy whilst resulting in similar glycaemic benefits. The investigators therefore hypothesize that a simplified meal approach (SMA) using the CamAPS FX system would achieve comparable glucose control compared with the use of the CamAPS FX system with ECC in YYA with T1D.

Official Title
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Simplified Meal Approach Study Using Hybrid Closed-loop Insulin Delivery in Youth and Young Adults With Type 1 Diabetes - a Randomised Controlled Two-centre Crossover Trial

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: SMA bolus option
* Device: Exactly estimated carbohydrate content bolus option


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Type 1 diabetes as defined by the World Health Organization for at least 6 months Age between 12 and 20 years (inclusive) Proficient use of continuous glucose monitoring (CGM) or flash glucose monitoring (FGM) for at least 5 days in the past Glycated hemoglobin A1c (HbA1c) ≤12% The participant is willing to wear closed-loop devices The participant is willing to follow study specific instructions Negative urine-pregnancy test in sexually active female participants of childbearing potential at screening-visit Exclusion Criteria: Any physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results Known or suspected allergy against insulin Participant is pregnant or breast feeding or planning pregnancy within next 6.5 months Severe visual impairment Severe hearing impairment Lack of reliable telephone facility for contact Concomitant participation in another trial that interferes with the normal conduct of the study and interpretation of the study results Participant not proficient in German

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 20 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simplified carbohydrate estimation first, exact carbohydrate estimation second<br>In the first study period, participants will use the CamAPS FX system and adopt the simplified meal announcement (SMA) option to bolus for their meals. SMA comprises the selection of predefined carbohydrate quantities for meal insulin dosing. Meal carbohydrate contents will be set on an individual basis at the baseline visit. In the second study period, Participants will use the CamAPS FX system and insert the estimated grams of carbohydrates into the application as exactly as possible in order to bolus for their meals. | Device: SMA bolus option<br>* SMA comprises the selection of predefined carbohydrate quantities for meal insulin dosing. Meal carbohydrate contents will be set on an individual basis at the baseline visit.<br>* Other names: Simplified meal announcement bolus option;Device: Exactly estimated carbohydrate content bolus option<br>* The carbohydrate content of meals is estimated in grams of carbohydrates prior to a meal bolus<br>|
| Experimental: Exact carbohydrate estimation first, simplified carbohydrate estimation second.<br>In the first study period, participants will use the CamAPS FX system and insert the estimated grams of carbohydrates into the application as exactly as possible in order to bolus for their meals. In the second study period, participants will use the CamAPS FX system and adopt the simplified meal announcement (SMA) option to bolus for their meals. SMA comprises the selection of predefined carbohydrate quantities for meal insulin dosing. Meal carbohydrate contents will be set on an individual basis at the baseline visit. | Device: SMA bolus option<br>* SMA comprises the selection of predefined carbohydrate quantities for meal insulin dosing. Meal carbohydrate contents will be set on an individual basis at the baseline visit.<br>* Other names: Simplified meal announcement bolus option;Device: Exactly estimated carbohydrate content bolus option<br>* The carbohydrate content of meals is estimated in grams of carbohydrates prior to a meal bolus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time with sensor glucose measurements between 3.9 and 10.0 mmol/L | The percentage of time with sensor glucose measurements between 3.9 and 10.0 mmol/L will be compared between both intervention arms. Primary analysis will be carried out according to a non-inferiority framework. | From the first day of the respective study period to 3 months thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time spent with sensor glucose values above target (>10.0 mmol/L) | Percentage of time spent with sensor glucose values above target (>10.0 mmol/L) | From the first day of the respective study period to 3 months thereafter | 
| Time spent with sensor glucose values >13.9 mmol/L (%) | Percentage of time spent with sensor glucose values >13.9 mmol/L (%) | From the first day of the respective study period to 3 months thereafter | 
| Time spent with sensor glucose measurements < 3.9 mmol/L | The percentage of time with sensor glucose measurements < 3.9 mmol/L (%) | From the first day of the respective study period to 3 months thereafter | 
| Time spent with sensor glucose measurements < 3.0 mmol/L | The percentage of time with sensor glucose measurements < 3.0 mmol/L (%) | From the first day of the respective study period to 3 months thereafter | 
| Time spent with sensor glucose measurements between < 3.9 mmol/L and 7.8 mmol/L (%) | The percentage of time with sensor glucose between < 3.9 mmol/L and 7.8 mmol/L (%) | From the first day of the respective study period to 3 months thereafter | 
| Mean sensor glucose level (mmol/L) | Mean of all sensor glucose levels (mmol/L) | From the first day of the respective study period to 3 months thereafter | 
| HbA1c | Glycated hemoglobin A1c (%) | At baseline and at the predefined study visits (3 months after the start of the respective periods) | 
| Mean peak postprandial glucose | Mean peak postprandial glucose (mmol/L) assessed within 180min following main meals (defined as carbohydrate amounts >25g entered into the CamAPS app by the participants). | From the first day of the respective study period to 3 months thereafter | 
| Coefficient of sensor glucose variation (%) | Coefficient of sensor glucose variation (%) | From the first day of the respective study period to 3 months thereafter | 
| Standard deviation of sensor glucose variation (mmol/L) | Standard deviation of sensor glucose variation (mmol/L) | From the first day of the respective study period to 3 months thereafter | 
| Glucose Management Indicator (%) | Glucose Management Indicator (%) | From the first day of the respective study period to 3 months thereafter | 
| Number of clinically significant hypoglycaemia (number of events with sensor glucose <3.9 mmol/L for at least 15min) | Number of events with sensor glucose <3.9 mmol/L for at least 15min | From the first day of the respective study period to 3 months thereafter | 
| Extended hypoglycaemia event rate (number of events with sensor glucose <3.9 mmol/L lasting at least 120min) | Number of events with sensor glucose <3.9 mmol/L lasting at least 120min | From the first day of the respective study period to 3 months thereafter | 
| Extended hyperglycaemia event rate (number of events with sensor glucose >13.9 mmol/L lasting at least 120min) | Number of events with sensor glucose >13.9 mmol/L lasting at least 120min | From the first day of the respective study period to 3 months thereafter | 
| Proportion of participants with sensor glucose in the target range (3.9 - 10.0 mmol/L for >70% of the time. | Proportion of participants with sensor glucose in the target range (3.9 - 10.0 mmol/L for >70% of the time. | From the first day of the respective study period to 3 months thereafter | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes, Youth, Adolescents, Artificial pancreas system, Meal announcement