Portable Artificial Pancreas Applied for Youth and Adolescents (PAPAYA 1)

The purpose of this study is to determine the performance of a bi-hormonal reactive closed-loop system in adolscents with type 1 diabetes mellitus. The percentage of time spent in the target range (3.9-10.0 mmol/L) is the main outcome and will be compared between the bi-hormonal closed-loop system and the current treatment of the patients. Also, safety parameters, pharmacodynamics and patient reported outcomes (expectations, trust and treatment satisfaction scores) are compared.

This study is a monocenter, randomized, cross-over trial with 20 subjects. The subjects will be randomized to receive either the open-loop therapy or the closed-loop therapy for the first two-week study period and switch to the alternate treatment with at least two weeks in between.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Device: Open-loop control; Device: Bi-hormonal closed-loop control

Detailed Description

Background of the study:

Inreda Diabetic B.V. (Goor, The Netherlands) developed a bi-hormonal reactive closed loop system to automate glucose regulation (artificial pancreas; AP) in patients with diabetes mellitus type 1. In previous studies, we tested the performance and safety of this bi-hormonal closed-loop system in an outpatient setting in patients with type 1 diabetes mellitus (T1DM) for a duration up to 2 weeks, leading to CE-marking of the system. The device is currently intended for insulin-dependent adult patients with diabetes. However, there is great need to improve glycaemic control in youth and adolescents with diabetes.

Objective of the study:

The main objective of this study is to determine the performance of the closed-loop system in adolescents with T1DM. Secondary objectives include: to assess the safety of the closed-loop system; to determine the time that the closed-loop algorithm is active; and to assess expectations and treatment satisfaction of the closed-loop system.

Study design:

This study is a monocenter randomized cross-over trial.

Study population:

The study population will comprise 20 patients with T1DM, between 12 and 18 years old, not having impaired awareness of hypoglycaemia, and who are treated with insulin therapy for at least 6 months. Patients receiving treatment with multiple daily injections (MDI) or continuous subcutaneous insulin injections (CSII), and in addition glucose monitoring using self-monitored blood glucose (SMBG), flash glucose monitoring (FGM) or continuous glucose monitoring (CGM) are included into the study.

Intervention:

The intervention includes 2 weeks of closed-loop control with the artificial pancreas (AP) of Inreda Diabetic. The device uses 2 subcutaneous glucose sensors, 2 subcutaneous infusion sets, and incorporates 2 pumps and a reactive closed-loop algorithm. During 4-6 days before the intervention the patients receive training on the use of the closed-loop system and will start using the device under close supervision. The control arm (open loop treatment) consists of the patient's standard therapy at home for 2 weeks.

Main study parameters/endpoints:

Main study parameter is the percentage of time spent in the target range (3.9-10.0 mmol/L), which will be compared between the open and closed-loop periods for each patient.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Arnhem, Gelderland, Netherlands, 6815 AD
      • Rijnstate Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with type 1 diabetes mellitus
• Twelve to eighteen years old;
• Treated with insulin therapy for at least 6 months;
• Willing and able to sign informed consent or to assent to study participation.

Exclusion Criteria:

• Impaired awareness of hypoglycaemia (score ≥ 4) according to Gold and/or Clarke questionnaire[6,7];
• BMI ≥ 35 kg/m2;
• Pregnancy and/or breastfeeding;
• HbA1c > 97 mmol/mol (11.0%);
• Use of acetaminophen (paracetamol) during the open loop or closed-loop period,as this may influence the sensor glucose measurements;
• Limited ability to see, hear or feel the alarm signals of the closed-loop system;
• Unwillingness to act in response to the alarm signals;
• Living alone during the night during the closed-loop period (the patient may ask someone to stay over temporarily);
• Expected poor internet connectivity regarding 24/7 tele monitoring;
• Any condition that the local investigator feels would interfere with trial participation or evaluation of the results.

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
Active Comparator: Open loop control; In this arm, the patients will use their usual diabetes therapy. Additionally, patients will wear a blinded DexcomG6 for data collection during the open loop period.	Device: Open-loop control; During open-loop control the patients will use their usual diabetes therapy. Aditionally, patients will wear a blinded Dexcom G6 for data collection during the open loop period.
Experimental: Bi-hormonal closed-loop control; In this arm, treatment consists of the bi-hormonal closed-loop system. A short acting insulin analogue (Humalog, 3 ml pre-filled cartridge, Eli Lilly) and glucagon (Glucagen, Novo Nordisk; 3.15 ml cartridge Accu-Chek Spirit, Roche) will be administered according to the closed-loop algorithm. Additionally, patients will wear a blinded DexcomG6 for data collection during the closed loop period.	Device: Bi-hormonal closed-loop control; During bi-hormonal closed-loop control insulin and glucagon are administered to the developed closed-loop algorithm. Aditionally, patients will wear a blinded Dexcom G6 for data collection during the closed loop period.; Other Names: Artificial Pancreas (AP); bi-hormonal AP system; AP5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in range	The proportion of time spent in the range of 3.9-10.0 mmol/L in %	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in hypoglycemia 1	The proportion of time spent in hypoglycemia (<3.9 mmol/L) in %	2 weeks
Time in hypoglycemia 2	The proportion of time spent in hypoglycemia (<3.0 mmol/L) in %	2 weeks
Time in hyperglycemia 1	The proportion of time spent in hyperglycemia (>10.0 mmol/L) in %	2 weeks
Time in hyperglycemia 2	The proportion of time spent in hyperglycemia (>13.9 mmol/L) in %	2 weeks
Mean glucose concentration	Mean glucose concentration in mmol/L	2 weeks
Median glucose concentration	Median glucose concentration in mmol/L	2 weeks
Glycemic variability - Coefficient of variation	Coefficient of variation (standard deviation divided by the mean) in %	2 weeks
Glycemic variability - Interquartile range	Interquartile range in mmol/L	2 weeks
Mean glucose concentration during the day	Mean glucose concentration in mmol/L during the day (6AM - 12PM)	2 weeks
Mean glucose concentration during the night (12PM - 6AM)	Mean glucose concentration in mmol/L during the night (12PM - 6AM)	2 weeks
Median glucose concentration during the day (6AM - 12PM)	Median glucose concentration in mmol/L during the day (6AM - 12PM)	2 weeks
Median glucose concentration during the night (12PM - 6AM)	Median glucose concentration in mmol/L during the night (12PM - 6AM)	2 weeks
Time spent in hypoglycemia during the night	Time spent in hypoglycemia (<3.9 mmol/L) during the night (12PM - 6AM) in %	2 weeks
Time spent in hyperglycemia during the night	Time spent in hyperglycemia (>10.0 mmol/L) during the night (12PM - 6AM) in %	2 weeks
Time spent in euglycemia during the night	Time spent in euglycemia (<3.9 mmol/L and <10 mmol/L) during the night (12PM - 6AM) in %	2 weeks
Time spent in hypoglycemia during the day	Time spent in hypoglycemia (<3.9 mmol/L) during the day (6AM - 12PM) in %	2 weeks
Time spent in hyperglycemia during the day	Time spent in hyperglycemia (>10.0 mmol/L) during the day (6AM - 12PM) in %	2 weeks
Time spent in euglycemia during the day	Time spent in euglycemia (<3.9 mmol/L and <10 mmol/L) during the day (6AM - 12PM) in %	2 weeks
Algorithm active time	Time that the closed-loop algorithm is active in %	2 weeks
Expectations	INSPIRE questionnaire (only for closed loop)	2 weeks
Trust	TAS questionnaire (only for closed loop)	2 weeks
Satisfaction	DTSQ questionnaire (for open loop and closed loop)	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Weight in kg	Baseline
Gender	Gender (M/F)	Baseline
Length	Length in cm	Baseline
HbA1c plasma concentration	HbA1c plasma concentration in mmol/mol	Baseline
Current medication use	List of medication names and corresponding dosages	Baseline
Insulin dose	Daily average of insulin in units	2 weeks
Glucagon dose	Daily average of glucagon in units	2 weeks

Collaborators and Investigators

• Sponsor: Inreda Diabetic B.V.
• Collaborators: Stichting Robopump; Rijnstate ziekenhuis; Kinder Diabetes Centrum Nijmegen
• Investigators: Principal Investigator: Arianne Bon, MD, PhD, Rijnstate Ziekenhuis

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2022
• Primary Completion (Actual): May 19, 2023
• Study Completion (Actual): May 19, 2023

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Gastrointestinal Agents; Pancrelipase
• Other Study ID Numbers: NL79829.000.22

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