Algorithm to Control Postprandial, Post Exercise and Night Glucose Excursions in a Portable Closed Loop Format, (APPEL5)

Algorithm to Control Postprandial, Post Exercise and Night Glucose Excursions in a Portable Closed Loop Format, APPEL 5

In previous studies, the investigators tested the feasibility of a bi-hormonal reactive closed loop system without mealtime announcement. This system for automated control of blood glucose in patients with type 1 diabetes was tested in the clinical research center (APPEL 1 and 2) as well as at the home of the patients (APPEL 3 and 4). After the APPEL 4 study some improvements have been made to the miniaturized prototype to allow patients to operate the system independently and additional risk control measures were included. The main objective of this study is to assess the efficacy of this improved closed loop system.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Device: Insulin pump therapy (with or without glucose sensor); Device: Artificial pancreas (Inreda Diabetic)

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Arnhem, Gelderland, Netherlands, 6815 AD
      • Rijnstate Hospital
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Academic Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with diabetes mellitus type 1;
• Treated with SAP or CSII for a minimum of 6 months;
• Willing and able to sign informed consent.

Exclusion Criteria:

• Impaired awareness of hypoglycemia (score ≥ 4) according to Gold and/or Clarke questionnaire;
• BMI > 35 kg/m2;
• HbA1c > 97 mmol/mol (=11.0 %);
• Use of heparin, coumarin derivatives or oral corticosteroids;
• Use of acetaminophen during the open loop or closed loop period, as this may influence the sensor glucose measurements;
• Limited ability to see, and to hear or feel alarm signals of the closed loop system;
• Skin condition prohibiting needle insertion;
• Pregnancy and/or breastfeeding;
• Living alone during the night during the closed loop period (the patient may ask someone to stay over temporarily);
• Expected poor connectivity with internet regarding 24/7 tele monitoring;
• Any condition that the local investigator feels would have interfere with trial participation or the 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; 14 days patient-managed Insulin pump therapy (with or without glucose sensor) with blinded continuous glucose monitoring	Device: Insulin pump therapy (with or without glucose sensor); Patients' own insulin pump with fast-acting insulin analog and optionally with own glucose sensor; Other Names: Continuous subcutaneous insulin infusion (CSII); Sensor augmented pump therapy (SAP)
Experimental: Closed loop; 4-6 training + 14 days automated blood glucose control with the Artificial pancreas (Inreda Diabetic)	Device: Artificial pancreas (Inreda Diabetic); Bi-hormonal reactive closed loop system without mealtime announcement; Other Names: Closed loop therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in target	Proportion of time spent in the target range (3.9-10 mmol/l)	Week 1-2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in hypoglycemia 1	Proportion of time spent in hypoglycemia (<3.9 mmol/l)	Week 1-2 / Week 1 / Week 2
Time in hypoglycemia 2	Proportion of time spent in hypoglycemia (<3.3 mmol/l)	Week 1-2 / Week 1 / Week 2
Time in hyperglycemia 1	Proportion of time spent in hyperglycemia (>10 mmol/l)	Week 1-2 / Week 1 / Week 2
Time in hyperglycemia 2	Proportion of time spent in hyperglycemia (>13.9 mmol/l)	Week 1-2 / Week 1 / Week 2
Hypoglycemic events	Number of carbohydrate-treated hypoglycemic events	Week 1-2 / Week 1 / Week 2
Mean or median glucose	Mean or median sensor glucose concentration	Week 1-2 / Week 1 / Week 2
Mean or median day glucose	Mean or median sensor glucose concentration	Day time: Week 1-2 / Week 1 / Week 2
Mean or median night glucose	Mean or median sensor glucose concentration	Night time: Week 1-2 / Week 1 / Week 2
Mean or median postprandial glucose	Mean or median sensor glucose concentration	Postprandial: Week 1-2 / Week 1 / Week 2
Glycemic variability 1	Interquartile range (IQR)	Week 1-2 / Week 1 / Week 2
Glycemic variability 2	Coefficient of variation (CV)	Week 1-2 / Week 1 / Week 2
Glycemic variability 3	Low blood glucose index (LBGI)	Week 1-2 / Week 1 / Week 2
Glycemic variability 4	High blood glucose index (HBGI)	Week 1-2 / Week 1 / Week 2
Glycemic variability 5	Blood glucose risk index (BGRI)	Week 1-2 / Week 1 / Week 2
Time in target	Proportion of time spent in the target range (3.9-10 mmol/l)	Week 1 / Week 2
PAID: Problem Areas In Diabetes questionnaire	Total score; Scale 0 (no problems) to 80 (big problems)	Baseline / End week 2
EQ5D: EuroQol 5 Dimensions questionnaire	Quality of life measure; Scale 1 ("no problem) to 5 ("extreme problems")	Baseline / End week 2
DTSQ-status: Diabetes Treatment Satisfaction Questionnaire	Total score: Scale 0 (negative) to 36 (positive)	Baseline / End week 2
DTSQ-change: Diabetes Treatment Satisfaction Questionnaire	Change in DTSQ; Total score: Scale -18 (negative) to 18 (positive)	End week 2
Algorithm active time	Percentage of time that the closed loop algorithm is active	Week 1-2 (closed loop only)
Usability score	Questionnaire: Mobile Phone Usability Questionnaire (MPUQ); Total score: Scale 62 (low level of usability) to 310 (higher level of usability)	End week 2 (closed loop only)
Glucose measurement performance	MARD	Day 3, 4 or 5 of the training period prior to the closed loop

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight		Baseline
Length		Baseline
Demographic variables		Baseline
HbA1c plasma concentration		Baseline
Meals	Carbohydrate intake	Week 1-2
Physical activity 1	Number of exercise moments per intensity category ("light", "moderate", "heavy'" )	Week 1-2
Physical activity 2	Duration of exercise moments per intensity category ("light", "moderate", "heavy'" )	Week 1-2
Physical activity 3	Total number of exercise moments	Week 1-2
Physical activity 4	Total duration of exercise moments	Week 1-2
Insulin dose	Daily average	Week 1-2
Glucagon dose	Daily average	Week 1-2

Collaborators and Investigators

• Sponsor: J.H. DeVries
• Collaborators: Rijnstate Hospital; Inreda Diabetic B.V.
• Investigators: Principal Investigator: J.H. DeVries, MD PhD, Academisch Medisch Centrum, Universiteit van Amsterdam

Publications and helpful links

General Publications

• van Bon AC, Luijf YM, Koebrugge R, Koops R, Hoekstra JB, DeVries JH. Feasibility of a portable bihormonal closed-loop system to control glucose excursions at home under free-living conditions for 48 hours. Diabetes Technol Ther. 2014 Mar;16(3):131-6. doi: 10.1089/dia.2013.0166. Epub 2013 Nov 13.
• Blauw H, van Bon AC, Koops R, DeVries JH; , on behalf of the PCDIAB consortium. Performance and safety of an integrated bihormonal artificial pancreas for fully automated glucose control at home. Diabetes Obes Metab. 2016 Jul;18(7):671-7. doi: 10.1111/dom.12663. Epub 2016 Apr 25.
• Blauw H, Onvlee AJ, Klaassen M, van Bon AC, DeVries JH. Fully Closed Loop Glucose Control With a Bihormonal Artificial Pancreas in Adults With Type 1 Diabetes: An Outpatient, Randomized, Crossover Trial. Diabetes Care. 2021 Mar;44(3):836-838. doi: 10.2337/dc20-2106. Epub 2021 Jan 4.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2019
• Primary Completion (Actual): September 12, 2019
• Study Completion (Actual): September 12, 2019

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: February 27, 2019
• First Posted (Actual): February 28, 2019

Study Record Updates

• Last Update Posted (Actual): October 22, 2019
• Last Update Submitted That Met QC Criteria: October 21, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Glucose control; Artificial pancreas
• 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; Gastrointestinal Agents; Insulin; Insulin, Globin Zinc; Pancrelipase
• Other Study ID Numbers: NL55693.018.15

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