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The Artificial Pancreas in Very Young Children With T1D - Pilot (KidsAP01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03101865
Recruitment Status : Completed
First Posted : April 5, 2017
Last Update Posted : June 6, 2018
Sponsor:
Collaborators:
European Commission
Medtronic
Cambridge University Hospitals NHS Foundation Trust
The Leeds Teaching Hospitals NHS Trust
University of Luxembourg
University of Leipzig
Medical University of Graz
Medical University Innsbruck
Medical University of Vienna
Jaeb Center for Health Research
Information provided by (Responsible Party):
Dr Roman Hovorka, University of Cambridge

Brief Summary:

The suggested clinical trial is part of the KidsAP project funded by the European Commission's Horizon 2020 Framework Programme. The project evaluates the use of the Artificial Pancreas (or closed loop systems) in very young children with type 1 diabetes (T1D) aged 1 to 7 years. The suggested trial is a feasibility study to pilot the setup of a large-scale outcome trial and to address the specific needs of this population. The results of the pilot trial will feed into the design of the outcome study.

In this study the investigators will compare closed loop insulin delivery using standard strength insulin to closed loop use with diluted insulin in very young children with T1D. Diluted insulin is a standard treatment approach for children with low insulin requirements. The investigators hypothesize that diluted insulin will lead to more stable glucose levels by reducing inaccuracies accentuated by delivery of minute amounts of insulin (frequently less than 0.1U/h [1μl/h with standard strength insulin] in small children compared to 1U/h in adults). These inaccuracies may result from pump plunger micro-jumps, tissues pressure build-up, and infusion set kinking. This study builds on previous and on-going studies of closed loop systems that have been performed in Cambridge in children and adolescents with T1D in clinical research facilities and in the home setting.

The study adopts an open-label, multi-centre, multinational, randomised, two-period crossover design contrasting closed loop glucose control using diluted insulin and closed loop using standard insulin strength under free-living home conditions. The two intervention periods will last 3 weeks each with a 1 to 4 weeks washout period in between. The order of the two interventions will be random. A total of up to 30 young children aged 1 to 7 years with T1D on insulin pump therapy will be recruited through outpatient diabetes clinics at participating clinical centres to allow for 24 completed subjects available for assessment in each of the study arms.

Prior to the use of study devices, participants and parents/guardians will receive appropriate training by the research team on the safe use of the study pump and continuous glucose monitoring system, and the hybrid closed loop insulin delivery system. Carers at nursery or school may also receive training by the study team if required. During the intervention periods, subjects and parents/guardians will use the closed loop system for 21 days under free-living conditions in their home and nursery/school environment without remote monitoring or supervision by research staff.

The primary outcome is time spent in target range between 3.9 and 10.0 mmol/l as recorded by CGM. Secondary outcomes are the time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises the tabulation of severe hypoglycaemic episodes.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Device: FlorenceM Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open-label, Multi-centre, Randomised, 2-period Cross-over Study to Assess the Efficacy and Safety of Closed Loop Insulin Delivery Using Diluted Insulin in Comparison With Closed Loop With Non-diluted Insulin Over 21 Days in Children With Type 1 Diabetes Aged 1 to 7 Years in the Home Setting
Actual Study Start Date : August 8, 2017
Actual Primary Completion Date : May 11, 2018
Actual Study Completion Date : May 11, 2018


Arm Intervention/treatment
Experimental: Closed loop with diluted insulin
Unsupervised home use of day and night automated closed loop insulin delivery system (FlorenceM) combined with pump suspend feature using DILUTED insulin aspart over 3 weeks.
Device: FlorenceM
The automated closed loop system (FlorenceM) will consist of: Next generation sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Enlite 3 family real time CGM and glucose suspend feature. An Android smartphone containing the Cambridge model predictive algorithm and communicating wirelessly with the insulin pump using a proprietary translator device.

Active Comparator: Closed loop with standard insulin strength
Unsupervised home use of day and night automated closed loop insulin delivery system (FlorenceM) combined with pump suspend feature using STANDARD strength insulin aspart over 3 weeks.
Device: FlorenceM
The automated closed loop system (FlorenceM) will consist of: Next generation sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Enlite 3 family real time CGM and glucose suspend feature. An Android smartphone containing the Cambridge model predictive algorithm and communicating wirelessly with the insulin pump using a proprietary translator device.




Primary Outcome Measures :
  1. Time in target (3.9 to 10.0mmol/l) (70 to 180 mg/dl) [ Time Frame: 3-week home stay ]
    Percentage of time spent with sensor glucose readings in the target glucose range from 3.9 to 10.0 mmol// (70 to 180 mg/dl)


Secondary Outcome Measures :
  1. Time spent below target glucose (3.9mmol/l)(70mg/dl) [ Time Frame: 3-week home stay ]
    Percentage of time spent with sensor glucose readings below target glucose (3.9mmol/l)(70mg/dl)

  2. Time spent above target glucose (10.0mmol/l) (180mg/dl) [ Time Frame: 3-week home stay ]
    Percentage of time spent with sensor glucose readings above target glucose (10.0mmol/l) (180mg/dl)

  3. Average glucose [ Time Frame: 3-week home stay ]
    Average of sensor glucose levels

  4. Standard deviation of glucose levels [ Time Frame: 3-week home stay ]
    Standard deviation of sensor glucose levels

  5. Coefficient of variation of glucose levels [ Time Frame: 3-week home stay ]
    Coefficient of variation of sensor glucose levels

  6. Time with glucose levels < 3.5mmol/l (63 mg/dl) [ Time Frame: 3-week home stay ]
    Percentage of time spent with glucose levels < 3.5mmol/l (63 mg/dl)

  7. Time with glucose levels <2.8mmol/l (50mg/dl) [ Time Frame: 3-week home stay ]
    Percentage of time spent with glucose levels <2.8mmol/l (50mg/dl)

  8. Time with glucose levels in significant hyperglycaemia [ Time Frame: 3-week home stay ]
    Percentage of time spent with glucose levels in significant hyperglycaemia (glucose levels > 16.7mmol/l) (300mg/dl)

  9. Total daily insulin dose [ Time Frame: 3-week home stay ]
    Average total daily insulin requirements

  10. Daily basal insulin dose [ Time Frame: 3-week home stay ]
    Average daily basal insulin requirements

  11. Daily bolus insulin dose [ Time Frame: 3-week home stay ]
    Average daily bolus insulin requirements

  12. AUC of glucose below 3.5mmol/l (63mg/dl) [ Time Frame: 3-week home stay ]
    Area under the curve of sensor glucose readings below 3.5mmol/l (63mg/dl)


Other Outcome Measures:
  1. Number of episodes of severe hypoglycaemia [ Time Frame: 3-week home stay ]
    Safety evaluation

  2. Number of subjects experiencing severe hypoglycaemia [ Time Frame: 3-week home stay ]
    Safety evaluation

  3. Frequency of diabetic ketoacidosis [ Time Frame: 3-week home stay ]
    Safety evaluation

  4. Frequency and nature of other adverse events or serious adverse events [ Time Frame: 3-week home stay ]
    Safety evaluation

  5. Percentage of time of closed-loop operations [ Time Frame: 3-week home stay ]
    Utility evaluation

  6. Percentage of time of CGM availability [ Time Frame: 3-week home stay ]
    Utility evaluation



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 7 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 1 and 7 years of age (inclusive)
  2. Type 1 diabetes as defined by WHO for at least 6 months
  3. Insulin pump user (with or without continuous glucose monitoring or flash glucose monitoring system) for at least 3 months, with subject/carer good knowledge of insulin self-adjustment as judged by the investigator
  4. Treated with rapid acting insulin analogue insulin Aspart (Novo Nordisk, Bagsvaerd, Denmark)
  5. Subject/carer is willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements taken every day
  6. Screening HbA1c ≤ 11% (97mmol/mol)
  7. Willing to wear glucose sensor
  8. Willing to wear closed loop system 24/7
  9. The subject/carer is willing to follow study specific instructions
  10. The subject/carer is willing to upload pump and CGM data at regular intervals

Exclusion Criteria:

  1. Physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
  2. Untreated coeliac disease or thyroid disease based on local investigations prior to study enrolment
  3. Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids
  4. Known or suspected allergy to insulin
  5. Recurrent incidents of severe hypoglycaemia (>2 episodes) during the previous 6 months [severe hypoglycaemia is defined as an event associated with a seizure or loss of consciousness]
  6. Unwilling to avoid regular use of acetaminophen
  7. Carer's lack of reliable telephone facility for contact
  8. Total daily insulin dose ≥ 2 IU/kg/day
  9. Subject/carer's severe visual impairment
  10. Subject/carer's severe hearing impairment
  11. Medically documented allergy towards the adhesive (glue) of plasters or subject is unable to tolerate tape adhesive in the area of sensor placement
  12. Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located in parts of the body which could potentially be used for localisation of the glucose sensor)
  13. Sickle cell disease, haemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
  14. Plan to receive red blood cell transfusion or erythropoietin over the course of study participation
  15. Subject/carer not proficient in English (UK) or German (Germany, Austria, Luxembourg) or French (Luxembourg)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03101865


Locations
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Austria
Department of Pediatrics and Adolescent Medicine, Medical University of Graz
Graz, Austria, A-8036
Department of Pediatrics I, Medical University of Innsbruck
Innsbruck, Austria, A-6020
Deptartment of Pediatrics, Medical University of Vienna
Vienna, Austria, A-1090
Germany
Division for Paediatric Diabetology, University of Leipzig
Leipzig, Germany, D-04103
Luxembourg
Clinique Pédiatrique de Luxembourg
Luxembourg, Luxembourg, L-1210
United Kingdom
University of Cambridge
Cambridge, United Kingdom, CB2 0QQ
St James's University Hospital
Leeds, United Kingdom, LS9 7TF
Sponsors and Collaborators
University of Cambridge
European Commission
Medtronic
Cambridge University Hospitals NHS Foundation Trust
The Leeds Teaching Hospitals NHS Trust
University of Luxembourg
University of Leipzig
Medical University of Graz
Medical University Innsbruck
Medical University of Vienna
Jaeb Center for Health Research
Investigators
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Study Director: Roman Hovorka, PhD Department of Paediatrics, University of Cambridge, UK
Principal Investigator: Carlo Acerini, MD Department of Paediatrics, University of Cambridge, UK
Principal Investigator: Carine de Beaufort, PhD Clinique Pédiatrique de Luxembourg, University of Luxembourg, Luxembourg
Principal Investigator: Fiona Campbell, MD St James's University Hospital, Leeds, UK
Principal Investigator: Elke Fröhlich-Reiterer, MD Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
Principal Investigator: Sabine Hofer, MD Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
Principal Investigator: Thomas Kapellen, MD Division for Paediatric Diabetology, University of Leipzig, Leipzig, Germany
Principal Investigator: Birgit Rami-Merhar, MD Deptartment of Pediatrics, Medical University of Vienna, Vienna, Austria
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dr Roman Hovorka, Director of Research, University of Cambridge
ClinicalTrials.gov Identifier: NCT03101865    
Other Study ID Numbers: KidsAP01
First Posted: April 5, 2017    Key Record Dates
Last Update Posted: June 6, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Fully anonymised data may be shared with third parties (EU or non-EU based) for the purposes of advancing management and treatment of diabetes.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr Roman Hovorka, University of Cambridge:
Type 1 diabetes
Artificial Pancreas
Closed-loop glucose control
Very young children
Continuous subcutaneous insulin infusion
Continuous glucose monitoring
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases