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

Primary Purpose

Diabetes Mellitus, Type 1

Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Insulin pump therapy (with or without glucose sensor)
Artificial pancreas (Inreda Diabetic)
Sponsored by
J.H. DeVries
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Artificial pancreas, Glucose control

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rijnstate Hospital
  • Academic Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Open loop

Closed loop

Arm Description

14 days patient-managed Insulin pump therapy (with or without glucose sensor) with blinded continuous glucose monitoring

4-6 training + 14 days automated blood glucose control with the Artificial pancreas (Inreda Diabetic)

Outcomes

Primary Outcome Measures

Time in target
Proportion of time spent in the target range (3.9-10 mmol/l)

Secondary Outcome Measures

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

Full Information

First Posted
February 21, 2019
Last Updated
October 21, 2019
Sponsor
J.H. DeVries
Collaborators
Rijnstate Hospital, Inreda Diabetic B.V.
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1. Study Identification

Unique Protocol Identification Number
NCT03858062
Brief Title
Algorithm to Control Postprandial, Post Exercise and Night Glucose Excursions in a Portable Closed Loop Format,
Acronym
APPEL5
Official Title
Algorithm to Control Postprandial, Post Exercise and Night Glucose Excursions in a Portable Closed Loop Format, APPEL 5
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
March 10, 2019 (Actual)
Primary Completion Date
September 12, 2019 (Actual)
Study Completion Date
September 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
J.H. DeVries
Collaborators
Rijnstate Hospital, Inreda Diabetic B.V.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
Keywords
Artificial pancreas, Glucose control

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Open loop
Arm Type
Active Comparator
Arm Description
14 days patient-managed Insulin pump therapy (with or without glucose sensor) with blinded continuous glucose monitoring
Arm Title
Closed loop
Arm Type
Experimental
Arm Description
4-6 training + 14 days automated blood glucose control with the Artificial pancreas (Inreda Diabetic)
Intervention Type
Device
Intervention Name(s)
Insulin pump therapy (with or without glucose sensor)
Other Intervention Name(s)
Continuous subcutaneous insulin infusion (CSII), Sensor augmented pump therapy (SAP)
Intervention Description
Patients' own insulin pump with fast-acting insulin analog and optionally with own glucose sensor
Intervention Type
Device
Intervention Name(s)
Artificial pancreas (Inreda Diabetic)
Other Intervention Name(s)
Closed loop therapy
Intervention Description
Bi-hormonal reactive closed loop system without mealtime announcement
Primary Outcome Measure Information:
Title
Time in target
Description
Proportion of time spent in the target range (3.9-10 mmol/l)
Time Frame
Week 1-2
Secondary Outcome Measure Information:
Title
Time in hypoglycemia 1
Description
Proportion of time spent in hypoglycemia (<3.9 mmol/l)
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Time in hypoglycemia 2
Description
Proportion of time spent in hypoglycemia (<3.3 mmol/l)
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Time in hyperglycemia 1
Description
Proportion of time spent in hyperglycemia (>10 mmol/l)
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Time in hyperglycemia 2
Description
Proportion of time spent in hyperglycemia (>13.9 mmol/l)
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Hypoglycemic events
Description
Number of carbohydrate-treated hypoglycemic events
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Mean or median glucose
Description
Mean or median sensor glucose concentration
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Mean or median day glucose
Description
Mean or median sensor glucose concentration
Time Frame
Day time: Week 1-2 / Week 1 / Week 2
Title
Mean or median night glucose
Description
Mean or median sensor glucose concentration
Time Frame
Night time: Week 1-2 / Week 1 / Week 2
Title
Mean or median postprandial glucose
Description
Mean or median sensor glucose concentration
Time Frame
Postprandial: Week 1-2 / Week 1 / Week 2
Title
Glycemic variability 1
Description
Interquartile range (IQR)
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Glycemic variability 2
Description
Coefficient of variation (CV)
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Glycemic variability 3
Description
Low blood glucose index (LBGI)
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Glycemic variability 4
Description
High blood glucose index (HBGI)
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Glycemic variability 5
Description
Blood glucose risk index (BGRI)
Time Frame
Week 1-2 / Week 1 / Week 2
Title
Time in target
Description
Proportion of time spent in the target range (3.9-10 mmol/l)
Time Frame
Week 1 / Week 2
Title
PAID: Problem Areas In Diabetes questionnaire
Description
Total score; Scale 0 (no problems) to 80 (big problems)
Time Frame
Baseline / End week 2
Title
EQ5D: EuroQol 5 Dimensions questionnaire
Description
Quality of life measure; Scale 1 ("no problem) to 5 ("extreme problems")
Time Frame
Baseline / End week 2
Title
DTSQ-status: Diabetes Treatment Satisfaction Questionnaire
Description
Total score: Scale 0 (negative) to 36 (positive)
Time Frame
Baseline / End week 2
Title
DTSQ-change: Diabetes Treatment Satisfaction Questionnaire
Description
Change in DTSQ; Total score: Scale -18 (negative) to 18 (positive)
Time Frame
End week 2
Title
Algorithm active time
Description
Percentage of time that the closed loop algorithm is active
Time Frame
Week 1-2 (closed loop only)
Title
Usability score
Description
Questionnaire: Mobile Phone Usability Questionnaire (MPUQ); Total score: Scale 62 (low level of usability) to 310 (higher level of usability)
Time Frame
End week 2 (closed loop only)
Title
Glucose measurement performance
Description
MARD
Time Frame
Day 3, 4 or 5 of the training period prior to the closed loop
Other Pre-specified Outcome Measures:
Title
Demographic variables
Time Frame
Baseline
Title
Weight
Time Frame
Baseline
Title
Length
Time Frame
Baseline
Title
HbA1c plasma concentration
Time Frame
Baseline
Title
Meals
Description
Carbohydrate intake
Time Frame
Week 1-2
Title
Physical activity 1
Description
Number of exercise moments per intensity category ("light", "moderate", "heavy'" )
Time Frame
Week 1-2
Title
Physical activity 2
Description
Duration of exercise moments per intensity category ("light", "moderate", "heavy'" )
Time Frame
Week 1-2
Title
Physical activity 3
Description
Total number of exercise moments
Time Frame
Week 1-2
Title
Physical activity 4
Description
Total duration of exercise moments
Time Frame
Week 1-2
Title
Insulin dose
Description
Daily average
Time Frame
Week 1-2
Title
Glucagon dose
Description
Daily average
Time Frame
Week 1-2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J.H. DeVries, MD PhD
Organizational Affiliation
Academisch Medisch Centrum, Universiteit van Amsterdam
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rijnstate Hospital
City
Arnhem
State/Province
Gelderland
ZIP/Postal Code
6815 AD
Country
Netherlands
Facility Name
Academic Medical Center
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1105 AZ
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24224750
Citation
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.
Results Reference
background
PubMed Identifier
26996542
Citation
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.
Results Reference
background
PubMed Identifier
33397767
Citation
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.
Results Reference
derived

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

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