Automated Insulin Delivery for Type 1 Diabetes - Beyond Glucose Metrics (AID-BEYOND)

AID-BEYOND: Automated Insulin Delivery for Type 1 Diabetes - Beyond Glucose Metrics

The goal of this clinical trial is to determine if transitioning to automated insulin delivery (AID) systems, can improve objectively measured sleep quality and quantity and alleviate cardiovascular risk factors in both children and adults diagnosed with type 1 diabetes. The main questions it aims to answer are:

• Does the intervention improve sleep efficiency as measured by the HomeSleepTest, EEG based device, 4 months after initiation?
• Can the use of AID treatment alleviate cardiovascular risk measured by heart rate variability (HRV), blood pressure and inflammatory markers?
• Researchers will compare AID systems to usual treatment, including both multiple daily injections and sensor augmented pumps to see if the above benefits can be achieved with AID in comparison. Participants will be randomized 1:1 to either start AID treatment or to continue their usual care. The study will be open label.

Participants will, at baseline and after 4 months:

• Have taken blood and urine samples to measure metabolic and inflammatory parameters
• Perform digital cognitive testing using the CANTAB software
• Fill out questionnaires related to quality of life, fear of hypoglycemia, hypoglycemia awareness, eating habits and sleep quality
• Wear a blinded CGM for 10 days
• Monitor sleep at home using the HomeSleepTest for 3 consecutive nights
• Wear a Holter monitor for 24 hours to determine HRV parameters
• Measure blood pressure for 24 hours at 30 min intervals
• Wear an ActiGraph for 7 days to assess sleep and activity, supported by daily electronic sleep diaries

Participants randomized to AID treatment will receive education in the use of the systems.

Virtual follow-up visits are scheduled at week 1, 5 and 9 for both control and intervention groups during the study, following baseline examinations.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Device: Automated insuling delivery system

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Z Sørensen, MD; Phone Number: +45 26836584; Email: michael.zaucha.soerensen.02@regionh.dk
• Study Contact Backup: Name: Natalie V Olesen, MD; Phone Number: +45 31627437; Email: nataol@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Steno Diabetes Center Aarhus
    • Contact: Kurt Kristensen
  • Silkeborg, Denmark, 8200
    • Recruiting
    • Diagnostisk Center, Regionshospitalet Silkeborg
    • Contact: Klavs W Hansen
  • Greater Copenhagen
    • Herlev, Greater Copenhagen, Denmark, 2730
      • Recruiting
      • Steno Diabetes Center Copenhagen
      • Contact: Kirsten Nørgaard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (Adults):

• Age ≥18 years
• Type 1 diabetes ≥3 years
• CGM or intermittently scanned CGM (isCGM) use ≥6 months
• Approval from the responsible health care provider (HCP) to start AID
• Specific AID system chosen ahead of screening after participant has been thoroughly informed

Inclusion Criteria (Children):

• Age 7-17 years
• Type 1 diabetes ≥6 months
• CGM or isCGM use ≥6 months
• Approval from the responsible HCP to start AID
• Specific AID system chosen ahead of screening after participant has been thoroughly informed

Exclusion Criteria:

• 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 commercial or open-source AID systems prior to study participation
• Daily use of paracetamol (acetaminophen)
• Breast-feeding, pregnancy or planning to become pregnant within 4 months
• Alcohol or drug abuse
• Severe cardiac disease
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adults with type 1 diabetes (intervention)	Device: Automated insuling delivery system; Closed-loop insulin pumps including MiniMed 780G, Tandom T2-slim x2 and YpsoCamAPS; Other Names: Closed-loop insulin pumps
No Intervention: Adults with type 1 diabetes (control)
Experimental: Children with type 1 diabetes (intervention); Pediatric population of 7-17 years, stratified 1:1 to two groups of 7-11 and ≥12 years accordingly	Device: Automated insuling delivery system; Closed-loop insulin pumps including MiniMed 780G, Tandom T2-slim x2 and YpsoCamAPS; Other Names: Closed-loop insulin pumps
No Intervention: Children with type 1 diabetes (control); Pediatric population of 7-17 years, stratified 1:1 to two groups of 7-11 and ≥12 years accordingly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in change from baseline to study end in sleep efficiency between the two groups.	Measured by HomeSleepTest for 3 consecutive days. Expressed in percentage.	Baseline and week 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total sleep duration	As measured by HomeSleepTest for 3 consequtive days. Expressed in minutes.	Baseline and week 18
Time in sleep stages	As measured by HomeSleepTest for 3 consequtive days. Expressed in minutes.	Baseline and week 18
Time in sleep stages	As measured by HomeSleepTest for 3 consequtive days. Expressed in percentages.	Baseline and week 18
Sleep latency	As measured by HomeSleepTest and ActiGraph for 3 consequtive days.Expressed in minutes	Baseline and week 18
Waking after sleep onset	As measured by HomeSleepTest and Actigraph for 3 consequtive days. Expressed in minutes	Baseline and week 18
24-hour blood pressure	Measured using SpaceLabs Ontrak. Expressed in mmHg, SBP, DBP and MAP means and differences at day/nighttime. Presence of nighttime dipping (defined as MAP reduction of 10% or more). Difference in dat day- and nighttime defined as time asleep measured by HST.	Baseline and week 18
Heart rate variability	Measured using Bittium Faros 180 holter monitors for 24 hours. Measured as standard deviation of NN intervals in milliseconds.	Baseline and week 18
Heart rate variability	Measured using Bittium Faros 180 holter monitors for 24 hours. Measured as root mean square of successive RR interval differences (rMSSD) in milliseconds.	Baseline and week 18
Heart rate variability	Measured using Bittium Faros 180 holter monitors for 24 hours. Measured as frequency-domain distribution absolute power in milliseconds squared.	Baseline and week 18
Heart rate variability	Measured using Bittium Faros 180 holter monitors for 24 hours. Measured as frequency-domain distribution relative power in percentage.	Baseline and week 18
Cognitive function	Measured using Cambridge Neuropsychological Test Automated Battery (CANTAB) with the Rapid Visual Information Processing test for both the adult and pediatric population.	Baseline and week 18
Cognitive function	Measured using Cambridge Neuropsychological Test Automated Battery (CANTAB) with the Delayed Matching to Sample test for both the adult and pediatric population.	Baseline and week 18
Cognitive function	Measured using Cambridge Neuropsychological Test Automated Battery (CANTAB) with the Spatial Working Memory test for the adult population only.	Baseline and week 18
Cognitive function	Measured using Cambridge Neuropsychological Test Automated Battery (CANTAB) with the Stop Signal Task test for the adult population only.	Baseline and week 18
Inflammatory markers	Defined in fold changes to expression of IL-1β, IL-6, IL-8, TNF-α, MCP-1, VEGF-α, CRP, ICAM-1, V-CAM-1, CRP. Assessed using multiplex ELISA analyses with MesoScale V-Plex and S-Plex plates.	Baseline and week 18
Hypoglycaemia Fear Survey scores	Possible scores between 0-44, higher scores mean more fear of hypoglycemia.	Baseline and week 18
Diabetes Distress Scale scores	Possible scores between 7-42, higher scores mean more diabetes distress.	Baseline and week 18
Pittsburgh Sleep Quality Index scores	Measured for adults only. Possible scores between 0-21, higher scores means more severe sleep issues.	Baseline and week 18
EuroQol 5-Domain scores	For adults the 5 Likert scale (5Q-5D-5L) will be used. For children the Young scale (5Q-5D-Y) scale will be used.	Baseline and week 18
5-item World Health Organization Well-Being Index (WHO-5) scores	Possible scores between 0-100. Lower scores means worse well-being.	Baseline and week 18
Sleep Screening Questionnaire Children and Adolescents (SSQ-CA) scores	Measured for children	Baseline and week 18
Sleep efficiency	Measured in percentages, assessed using 7 days of ActiGraph data, supported by daily electronic sleep diaries.	Baseline and week 18
Wake time after sleep onset	Measured in minutes, assessed using 7 days of ActiGraph data, supported by daily electronic sleep diaries.	Baseline and week 18

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c		Baseline and week 18
Time with glucose values in range of 3.9 -10.0 mmol/L	Measured in percentage.	Baseline and week 18
Time with glucose values < 3.9 mmol/l	Measured in percentage.	Baseline and week 18
Time with glucose values < 3.0 mmol/l	Measured in percentage.	Baseline and week 18
Time with glucose values > 10.0 mmol/l	Measured in percentage.	Baseline and week 18
Time with glucose values > 13.9 mmol/l	Measured in percentage.	Baseline and week 18
Sensor glucose	Measured as mmol/l with mean values and standard deviations	Baseline and week 18
Glucose coefficient of variation	Measured in percentage	Baseline and week 18
Time with rapid glucose change (> 1,5 mmol/l/15 min)	Measured in percentage.	Baseline and week 18
Bodyweight	Measured in kilograms.	Baseline and week 18
BMI standard deviation scores	Measured in the pediatric population.	Baseline and week 18
Total daily insulin dose	Measured in IE and assessed by 2-week insulin pump data downloads	Baseline and week 18
Total daily carbohydrate intake	Measured in grams and assessed by 2-week insulin pump data downloads	Baseline and week 18
Hypoglycaemia awareness status	Assessed by the Gold questionaire. Possible scores between 1-7 with 7 being worst hypoglycemia awareness.	Baseline and week 18
Hypoglycaemia awareness status	Assessed by the Clarke questionaire. Possible scores between 0-7 with 7 being worst hypoglycemia awareness.	Baseline and week 18
Hypoglycaemia awareness status	Assessed by the Pedersen-Bjergaard questionaire. Possible outcomes are "Aware", "Impaired" and "Unaware".	Baseline and week 18
Energy expenditure	Measured in kcal and assessed with 7 days of ActiGraph data.	Baseline and week 18
Physical activity level	Categorized as sedentary, light and moderate-to-vigorous levels, assessed with 7 days of ActiGraph data.	Baseline and week 18
Number of severe hypoglycaemia events	Expressed in diffence in number of events from baseline to end. Defined as cognitive impairment requiring external assistance for recovery.	Baseline and week 18

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Collaborators: Aarhus University Hospital
• Investigators: Principal Investigator: Kirsten Nørgaard, MD, Prof., Steno Diabetes Center Copenhagen; Principal Investigator: Kurt Kristensen, MD, PhD, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 11, 2024
• First Submitted That Met QC Criteria: June 17, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Sleep; Cognition; Cardiovascular risk; Type 1 Diabetes; T1D; Artificial pancreas; Automated insulin delivery; Closed-loop insulin pump; AID systems
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: H-23074743

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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