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

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

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

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).

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.

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.

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.

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.

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.

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).

Number of clinically significant hypoglycaemia (number of events with sensor glucose <3.9 mmol/L for at least 15min)

Extended hypoglycaemia event rate (number of events with sensor glucose <3.9 mmol/L lasting at least 120min)

Extended hyperglycaemia event rate (number of events with sensor glucose >13.9 mmol/L lasting at least 120min)

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.

Measurement of distress associated with the use of closed-loop insulin delivery using the Diabetes Distress questionnaire

HCS is a 9-item self-report scale that examines the degree to which people with diabetes feel able, secure, and comfortable regarding their ability to stay safe from hypoglycemic-related problems

Hypoglycaemia requiring third-party assistance to administer carbohydrates or other resuscitative action

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

Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland

Anonymised individual participant data will be shared after inquiry via a validated sharing platform (yet to be defined). Anonymised data packages will be available once the final study results are published in a peer-reviewed journal.