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

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).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: SMA bolus option; Device: Exactly estimated carbohydrate content bolus option

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
  • Zürich, Switzerland, 8032
    • Department of Paediatric Endocrinology and Diabetes, University Children's Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simplified carbohydrate estimation first, exact carbohydrate estimation second; 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; 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.; Other Names: Simplified meal announcement bolus option; Device: Exactly estimated carbohydrate content bolus option; The carbohydrate content of meals is estimated in grams of carbohydrates prior to a meal bolus
Experimental: Exact carbohydrate estimation first, simplified carbohydrate estimation second.; 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; 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.; Other Names: Simplified meal announcement bolus option; Device: Exactly estimated carbohydrate content bolus option; The carbohydrate content of meals is estimated in grams of carbohydrates prior to a meal bolus

What is the study measuring?

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
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
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
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
HbA1c	Glycated hemoglobin A1c (%)	At baseline and at the predefined study visits (3 months after the start of the respective periods)
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total daily basal insulin dose	Mean total daily basal insulin dose infused	From the first day of the respective study period to 3 months thereafter
Total daily bolus insulin dose	Mean total daily bolus insulin dose infused	From the first day of the respective study period to 3 months thereafter
Percentage of time of closed-loop operation including engagement with specific functionalities	Utility evaluation	From the first day of the respective study period to 3 months thereafter
Diabetes Distress Scale	Measurement of distress associated with the use of closed-loop insulin delivery using the Diabetes Distress questionnaire	At the predefined study visit 3 months after the start of the respective period.
Hypoglycaemia confidence scale	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	At the predefined study visit 3 months after the start of the respective period.
Psychosocial factors important to quality of life	These factors include anxiety, stress, depressions, etc.	At the predefined study visit 3 months after the start of the respective period.
Food Frequency Questionnaire to assess dietary intake habits	Dietary intake (quantity and quality)	At the predefined study visit 3 months after the start of the respective period.
Nature and severity of adverse events	AE including SADE and SAE	From the first day of the respective study period to 3 months thereafter
Number of severe hypoglycaemia events	Hypoglycaemia requiring third-party assistance to administer carbohydrates or other resuscitative action	From the first day of the respective study period to 3 months thereafter
Diabetic ketoacidosis	ADA definition	From the first day of the respective study period to 3 months thereafter
Significant ketonaemia	Value > 3.0 mmol/L	From the first day of the respective study period to 3 months thereafter

Collaborators and Investigators

• Sponsor: Lia Bally
• Collaborators: University of Zurich
• Investigators: Principal Investigator: Lia Bally, MD PhD, University Hospital of Bern

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2023
• Primary Completion (Actual): September 29, 2023
• Study Completion (Actual): September 29, 2023

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Adolescents; Type 1 Diabetes; Youth; Artificial pancreas system; Meal announcement
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: SMASH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: After publication of the study results in a peer-reviewed journal.
• IPD Sharing Access Criteria: Contact with and approval by the corresponding author
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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