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

• ClinicalTrials.gov Identifier: NCT03858062
• Recruitment Status: Completed
• First Posted: February 28, 2019
• Last Update Posted: October 22, 2019
• Sponsor: J.H. DeVries
• Collaborators: Rijnstate Hospital; Inreda Diabetic
• Information provided by (Responsible Party): J.H. DeVries, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 1	Device: Insulin pump therapy (with or without glucose sensor); Device: Artificial pancreas (Inreda Diabetic)	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Algorithm to Control Postprandial, Post Exercise and Night Glucose Excursions in a Portable Closed Loop Format, APPEL 5
• Actual Study Start Date: March 10, 2019
• Actual Primary Completion Date: September 12, 2019
• Actual Study Completion Date: September 12, 2019

Arms and Interventions

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 Name: Closed loop therapy

Outcome Measures

Primary Outcome Measures :

1. Time in target [ Time Frame: Week 1-2 ]
   Proportion of time spent in the target range (3.9-10 mmol/l)

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Demographic variables [ Time Frame: Baseline ]
2. Weight [ Time Frame: Baseline ]
3. Length [ Time Frame: Baseline ]
4. HbA1c plasma concentration [ Time Frame: Baseline ]
5. Meals [ Time Frame: Week 1-2 ]
   Carbohydrate intake
6. Physical activity 1 [ Time Frame: Week 1-2 ]

   Number of exercise moments per intensity category ("light", "moderate", "heavy'"

   )

7. Physical activity 2 [ Time Frame: Week 1-2 ]

   Duration of exercise moments per intensity category ("light", "moderate", "heavy'"

   )

8. Physical activity 3 [ Time Frame: Week 1-2 ]
   Total number of exercise moments
9. Physical activity 4 [ Time Frame: Week 1-2 ]
   Total duration of exercise moments
10. Insulin dose [ Time Frame: Week 1-2 ]
    Daily average
11. Glucagon dose [ Time Frame: Week 1-2 ]
    Daily average

Eligibility Criteria

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

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

Contacts and Locations

Locations

Netherlands

Rijnstate Hospital

Arnhem, Gelderland, Netherlands, 6815 AD

Academic Medical Center

Amsterdam, Noord-Holland, Netherlands, 1105 AZ

Sponsors and Collaborators

J.H. DeVries

Rijnstate Hospital

Inreda Diabetic

Investigators

• Principal Investigator: J.H. DeVries, MD PhD; Academisch Medisch Centrum, Universiteit van Amsterdam

More Information

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.

• Responsible Party: J.H. DeVries, Endocrinologist, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• ClinicalTrials.gov Identifier: NCT03858062
• Other Study ID Numbers: NL55693.018.15
• First Posted: February 28, 2019
• Last Update Posted: October 22, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by J.H. DeVries, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Artificial pancreas; Glucose control

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin; Insulin, Globin Zinc; Pancrelipase; Hypoglycemic Agents; Physiological Effects of Drugs; Gastrointestinal Agents