Type 1 Diabetes MellitusNCT03101865
The Artificial Pancreas in Very Young Children With T1D - Pilot (KidsAP01)
A study testing FlorenceM in people with Type 1 Diabetes Mellitus, run by University of Cambridge at 7 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 7 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- FlorenceM
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 7 sitesin 4 countries
- Study dates
- 8 Aug 2017to 11 May 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age between 1 and 7 years of age (inclusive)
- Type 1 diabetes as defined by WHO for at least 6 months
- 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
- Treated with rapid acting insulin analogue insulin Aspart (Novo Nordisk, Bagsvaerd, Denmark)
- Subject/carer is willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements taken every day
- Screening HbA1c ≤ 11% (97mmol/mol)
Show all 10Show fewer
- Willing to wear glucose sensor
- Willing to wear closed loop system 24/7
- The subject/carer is willing to follow study specific instructions
- The subject/carer is willing to upload pump and CGM data at regular intervals
Who cannot join
- 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
- Untreated coeliac disease or thyroid disease based on local investigations prior to study enrolment
- Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids
- Known or suspected allergy to insulin
- 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]
- Unwilling to avoid regular use of acetaminophen
Show all 15Show fewer
- Carer's lack of reliable telephone facility for contact
- Total daily insulin dose ≥ 2 IU/kg/day
- Subject/carer's severe visual impairment
- Subject/carer's severe hearing impairment
- Medically documented allergy towards the adhesive (glue) of plasters or subject is unable to tolerate tape adhesive in the area of sensor placement
- 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)
- Sickle cell disease, haemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
- Plan to receive red blood cell transfusion or erythropoietin over the course of study participation
- Subject/carer not proficient in English (UK) or German (Germany, Austria, Luxembourg) or French (Luxembourg)
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
Austria3 sites
Department of Pediatrics and Adolescent Medicine, Medical University of Graz
Graz, A-8036
Department of Pediatrics I, Medical University of Innsbruck
Innsbruck, A-6020
Deptartment of Pediatrics, Medical University of Vienna
Vienna, A-1090
United Kingdom2 sites
University of Cambridge
Cambridge, CB2 0QQ
St James's University Hospital
Leeds, LS9 7TF
Germany1 site
Division for Paediatric Diabetology, University of Leipzig
Leipzig, D-04103
About this study
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
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.
Read more
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.
Read the detailed description
Purpose of clinical trial:
This is a feasibility study to pilot the outcome study setup and to address the specific needs of the studied population by comparing closed loop insulin delivery using standard strength insulin (U-100) and diluted insulin. The results will feed into the design of a follow up outcome study. The investigators hypothesize that diluted insulin will lead to more stable glucose levels by reducing inaccuracies accentuated by delivery of small amounts of insulin (frequently less than 0.1U/h [1μl/h with standard strength insulin] in small children.
Study objectives:
The study objective is to evaluate the safety, efficacy and utility of day-and-night closed loop glucose control in young children with type 1 diabetes.
- EFFICACY: The objective is to assess the ability of a day-and-night hybrid closed loop system using diluted insulin to maintain CGM glucose levels within the target range of 3.9 to 10mmol/l (70 to 180mg/dl) in comparison with a hybrid closed loop system with standard insulin strength in young children with type 1 diabetes.
- SAFETY: The objective is to evaluate the safety of day-and-night closed loop using diluted insulin versus closed loop with non-diluted insulin in terms of episodes and severity of hypoglycaemia, and nature and severity of other adverse events.
- UTILITY: The objective is to determine the overall acceptability and duration of use of the closed loop system in this population.
Study Design:
The pilot study adopts an open-label, multi-centre, multinational, randomised, two-period crossover study design contrasting closed loop glucose control using diluted insulin and closed loop using standard insulin strength in young children with type 1 diabetes in the home setting. Two intervention periods will last 3 weeks each with 1 to 4 weeks washout period. The order of the two interventions will be random.
Participating clinical centres:
- Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Luxembourg, Luxembourg
- University of Leipzig, Leipzig, Germany
- Medical University of Graz, Graz, Austria
- Medical University of Innsbruck, Innsbruck, Austria
- Medical University of Vienna, Vienna, Austria
Sample Size:
24 participants randomised (2-5 participants per centre), equal proportion of those with total daily insulin dose ≤12 U/day and >12 U/day
Maximum duration of study for a subject: 14 weeks
Recruitment:
The subjects will be recruited through paediatric diabetes outpatient clinics at participating clinical centres (see above). Enrollment will target up to 30 (2-5 participants per centre) to allow for dropouts during run-in (approximately equal proportion of those with total daily insulin dose ≤12 U/day and >12 U/day).
Consent:
Written informed consent will be obtained from all parents/guardians and written assent from older children before any study related activities.
Baseline Assessment:
Eligible subjects will undergo a baseline evaluation including a blood sample for the measurement of HbA1c. Questionnaires will be completed by parents/guardians.
Pre-Study Training and Run-in:
Training sessions on the use of the study CGM and insulin pump will be provided by the research team. During a 2-4 week run-in period, subjects will use study CGM and insulin pump. For compliance and to assess the ability of the subject to use the study devices safely, at least 8 days of CGM data need to be recorded and safe use of study insulin pump demonstrated during the last 14 days of run-in period. The CGM data will also be used to assess baseline glucose control and may be used for treatment optimization as necessary.
Competency Assessment:
Competency on the use of study insulin pump and study CGM will be evaluated using a competency assessment tool developed by the research team. Training may be repeated if required.
Randomisation:
Eligible subjects will be randomised to the use of automated hybrid closed loop glucose system with diluted insulin or to closed loop with standard strength insulin for 21 days, with a 1-4 week washout period in between the two interventions.
- Closed loop with diluted insulin Training on the use of the closed loop system with diluted insulin will be provided by the research team. During this 2-4 hour session, subjects and parents/guardians will operate the system under the supervision of the clinical research team, practicalities around the use of diluted insulin will be discussed, and pump settings will be adjusted accordingly. Competency on the use of closed loop system will be evaluated. Thereafter, subjects and their parents/guardians will continue using the hybrid closed loop system with diluted insulin over 21 days at home.
- Closed loop with standard insulin strength:
Identical procedures as described above will be followed including training on the use of the closed loop system with standard strength insulin. Subjects will continue using the closed loop system with standard strength insulin at home over 21 days.
End of study assessments:
Study devices will be downloaded and returned. Participants will resume usual care using their pre-study insulin pump. A closed loop experience questionnaire will be completed by parents/guardians.
Procedures for safety monitoring during trial:
Standard operating procedures for monitoring and reporting of all adverse events will be in place, including serious adverse events (SAE) and specific adverse events (AE) such as severe hypoglycaemia.
Criteria for withdrawal of subjects on safety grounds:
A subject/guardian may terminate participation in the study at any time without necessarily giving a reason and without any personal disadvantage. An investigator can stop the participation of a subject after consideration of the benefit/risk ratio. Possible reasons are:
- Serious adverse events
- Non-compliance
- Serious protocol violation
- Decision by the investigator, or the sponsor, that termination is in the subject's best medical interest
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- FlorenceM
- Keywords
- Type 1 diabetes, Artificial Pancreas, Closed-loop glucose control, Very young children, Continuous subcutaneous insulin infusion, Continuous glucose monitoring
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlorenceMDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Closed loop with diluted insulin | Experimental | 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. Receives: Device: FlorenceM |
| Closed loop with standard insulin strength | Active comparator | 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. Receives: Device: FlorenceM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time in target (3.9 to 10.0mmol/l) (70 to 180 mg/dl)
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)
Measured: 3-week home stay
Secondary outcomes (12)
Time spent below target glucose (3.9mmol/l)(70mg/dl)
Percentage of time spent with sensor glucose readings below target glucose (3.9mmol/l)(70mg/dl)
Measured: 3-week home stay
Time spent above target glucose (10.0mmol/l) (180mg/dl)
Percentage of time spent with sensor glucose readings above target glucose (10.0mmol/l) (180mg/dl)
Measured: 3-week home stay
Average glucose
Average of sensor glucose levels
Measured: 3-week home stay
Standard deviation of glucose levels
Standard deviation of sensor glucose levels
Measured: 3-week home stay
Coefficient of variation of glucose levels
Coefficient of variation of sensor glucose levels
Measured: 3-week home stay
Time with glucose levels < 3.5mmol/l (63 mg/dl)
Percentage of time spent with glucose levels < 3.5mmol/l (63 mg/dl)
Measured: 3-week home stay
Time with glucose levels <2.8mmol/l (50mg/dl)
Percentage of time spent with glucose levels <2.8mmol/l (50mg/dl)
Measured: 3-week home stay
Time with glucose levels in significant hyperglycaemia
Percentage of time spent with glucose levels in significant hyperglycaemia (glucose levels > 16.7mmol/l) (300mg/dl)
Measured: 3-week home stay
Total daily insulin dose
Average total daily insulin requirements
Measured: 3-week home stay
Daily basal insulin dose
Average daily basal insulin requirements
Measured: 3-week home stay
Daily bolus insulin dose
Average daily bolus insulin requirements
Measured: 3-week home stay
AUC of glucose below 3.5mmol/l (63mg/dl)
Area under the curve of sensor glucose readings below 3.5mmol/l (63mg/dl)
Measured: 3-week home stay
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2017
- Study start8 Aug 2017
- Primary completion11 May 2018
- Study completion11 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Dr Roman Hovorka, University of Cambridge
- Investigators
- Roman Hovorka, PhD, Study director, Department of Paediatrics, University of Cambridge, UKCarlo Acerini, MD, Principal investigator, Department of Paediatrics, University of Cambridge, UKCarine de Beaufort, PhD, Principal investigator, Clinique Pédiatrique de Luxembourg, University of Luxembourg, LuxembourgFiona Campbell, MD, Principal investigator, St James's University Hospital, Leeds, UKElke Fröhlich-Reiterer, MD, Principal investigator, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, AustriaSabine Hofer, MD, Principal investigator, Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, AustriaThomas Kapellen, MD, Principal investigator, Division for Paediatric Diabetology, University of Leipzig, Leipzig, GermanyBirgit Rami-Merhar, MD, Principal investigator, Deptartment of Pediatrics, Medical University of Vienna, Vienna, Austria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03101865
- Sponsor's protocol ID
- KidsAP01
- Status last verified
- Feb 2018
- First submitted
- 30 Mar 2017
- Last updated
- 6 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Fully anonymised data may be shared with third parties (EU or non-EU based) for the purposes of advancing management and treatment of diabetes.
Publications
Elleri D, Allen JM, Tauschmann M, El-Khairi R, Benitez-Aguirre P, Acerini CL, Dunger DB, Hovorka R. Feasibility of overnight closed-loop therapy in young children with type 1 diabetes aged 3-6 years: comparison between diluted and standard insulin strength. BMJ Open Diabetes Res Care. 2014 Dec 11;2(1):e000040. doi: 10.1136/bmjdrc-2014-000040. eCollection 2014.
PubMed 25512874Ruan Y, Elleri D, Allen JM, Tauschmann M, Wilinska ME, Dunger DB, Hovorka R. Pharmacokinetics of diluted (U20) insulin aspart compared with standard (U100) in children aged 3-6 years with type 1 diabetes during closed-loop insulin delivery: a randomised clinical trial. Diabetologia. 2015 Apr;58(4):687-90. doi: 10.1007/s00125-014-3483-6. Epub 2014 Dec 24.
PubMed 25537835Thabit H, Tauschmann M, Allen JM, Leelarathna L, Hartnell S, Wilinska ME, Acerini CL, Dellweg S, Benesch C, Heinemann L, Mader JK, Holzer M, Kojzar H, Exall J, Yong J, Pichierri J, Barnard KD, Kollman C, Cheng P, Hindmarsh PC, Campbell FM, Arnolds S, Pieber TR, Evans ML, Dunger DB, Hovorka R; New Collective Author. Home Use of an Artificial Beta Cell in Type 1 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2129-2140. doi: 10.1056/NEJMoa1509351. Epub 2015 Sep 17.
PubMed 26379095Tauschmann M, Allen JM, Wilinska ME, Thabit H, Stewart Z, Cheng P, Kollman C, Acerini CL, Dunger DB, Hovorka R. Day-and-Night Hybrid Closed-Loop Insulin Delivery in Adolescents With Type 1 Diabetes: A Free-Living, Randomized Clinical Trial. Diabetes Care. 2016 Jul;39(7):1168-74. doi: 10.2337/dc15-2078. Epub 2016 Jan 6.
PubMed 26740634Tauschmann M, Allen JM, Wilinska ME, Thabit H, Acerini CL, Dunger DB, Hovorka R. Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Suboptimally Controlled Adolescents With Type 1 Diabetes: A 3-Week, Free-Living, Randomized Crossover Trial. Diabetes Care. 2016 Nov;39(11):2019-2025. doi: 10.2337/dc16-1094. Epub 2016 Sep 9.
PubMed 27612500Tauschmann M, Allen JM, Nagl K, Fritsch M, Yong J, Metcalfe E, Schaeffer D, Fichelle M, Schierloh U, Thiele AG, Abt D, Kojzar H, Mader JK, Slegtenhorst S, Barber N, Wilinska ME, Boughton C, Musolino G, Sibayan J, Cohen N, Kollman C, Hofer SE, Frohlich-Reiterer E, Kapellen TM, Acerini CL, de Beaufort C, Campbell F, Rami-Merhar B, Hovorka R; KidsAP Consortium. Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Very Young Children: A Multicenter, 3-Week, Randomized Trial. Diabetes Care. 2019 Apr;42(4):594-600. doi: 10.2337/dc18-1881. Epub 2019 Jan 28.
PubMed 30692242
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03101865
- Acronym / sponsor ID
- KidsAP01
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Type 1 diabetes, Artificial Pancreas, Closed-loop glucose control, Very young children, Continuous subcutaneous insulin infusion, Continuous glucose monitoring
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- 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
- Study start
- 8 Aug 2017 (actual)
- Primary completion
- 11 May 2018 (actual)
- Study completion
- 11 May 2018 (actual)
- First posted
- 5 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Purpose of clinical trial:
This is a feasibility study to pilot the outcome study setup and to address the specific needs of the studied population by comparing closed loop insulin delivery using standard strength insulin (U-100) and diluted insulin. The results will feed into the design of a follow up outcome study. The investigators hypothesize that diluted insulin will lead to more stable glucose levels by reducing inaccuracies accentuated by delivery of small amounts of insulin (frequently less than 0.1U/h [1μl/h with standard strength insulin] in small children.
Study objectives:
The study objective is to evaluate the safety, efficacy and utility of day-and-night closed loop glucose control in young children with type 1 diabetes.
- EFFICACY: The objective is to assess the ability of a day-and-night hybrid closed loop system using diluted insulin to maintain CGM glucose levels within the target range of 3.9 to 10mmol/l (70 to 180mg/dl) in comparison with a hybrid closed loop system with standard insulin strength in young children with type 1 diabetes.
- SAFETY: The objective is to evaluate the safety of day-and-night closed loop using diluted insulin versus closed loop with non-diluted insulin in terms of episodes and severity of hypoglycaemia, and nature and severity of other adverse events.
- UTILITY: The objective is to determine the overall acceptability and duration of use of the closed loop system in this population.
Study Design:
The pilot study adopts an open-label, multi-centre, multinational, randomised, two-period crossover study design contrasting closed loop glucose control using diluted insulin and closed loop using standard insulin strength in young children with type 1 diabetes in the home setting. Two intervention periods will last 3 weeks each with 1 to 4 weeks washout period. The order of the two interventions will be random.
Participating clinical centres:
- Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Luxembourg, Luxembourg
- University of Leipzig, Leipzig, Germany
- Medical University of Graz, Graz, Austria
- Medical University of Innsbruck, Innsbruck, Austria
- Medical University of Vienna, Vienna, Austria
Sample Size:
24 participants randomised (2-5 participants per centre), equal proportion of those with total daily insulin dose ≤12 U/day and >12 U/day
Maximum duration of study for a subject: 14 weeks
Recruitment:
The subjects will be recruited through paediatric diabetes outpatient clinics at participating clinical centres (see above). Enrollment will target up to 30 (2-5 participants per centre) to allow for dropouts during run-in (approximately equal proportion of those with total daily insulin dose ≤12 U/day and >12 U/day).
Consent:
Written informed consent will be obtained from all parents/guardians and written assent from older children before any study related activities.
Baseline Assessment:
Eligible subjects will undergo a baseline evaluation including a blood sample for the measurement of HbA1c. Questionnaires will be completed by parents/guardians.
Pre-Study Training and Run-in:
Training sessions on the use of the study CGM and insulin pump will be provided by the research team. During a 2-4 week run-in period, subjects will use study CGM and insulin pump. For compliance and to assess the ability of the subject to use the study devices safely, at least 8 days of CGM data need to be recorded and safe use of study insulin pump demonstrated during the last 14 days of run-in period. The CGM data will also be used to assess baseline glucose control and may be used for treatment optimization as necessary.
Competency Assessment:
Competency on the use of study insulin pump and study CGM will be evaluated using a competency assessment tool developed by the research team. Training may be repeated if required.
Randomisation:
Eligible subjects will be randomised to the use of automated hybrid closed loop glucose system with diluted insulin or to closed loop with standard strength insulin for 21 days, with a 1-4 week washout period in between the two interventions.
- Closed loop with diluted insulin Training on the use of the closed loop system with diluted insulin will be provided by the research team. During this 2-4 hour session, subjects and parents/guardians will operate the system under the supervision of the clinical research team, practicalities around the use of diluted insulin will be discussed, and pump settings will be adjusted accordingly. Competency on the use of closed loop system will be evaluated. Thereafter, subjects and their parents/guardians will continue using the hybrid closed loop system with diluted insulin over 21 days at home.
- Closed loop with standard insulin strength:
Identical procedures as described above will be followed including training on the use of the closed loop system with standard strength insulin. Subjects will continue using the closed loop system with standard strength insulin at home over 21 days.
End of study assessments:
Study devices will be downloaded and returned. Participants will resume usual care using their pre-study insulin pump. A closed loop experience questionnaire will be completed by parents/guardians.
Procedures for safety monitoring during trial:
Standard operating procedures for monitoring and reporting of all adverse events will be in place, including serious adverse events (SAE) and specific adverse events (AE) such as severe hypoglycaemia.
Criteria for withdrawal of subjects on safety grounds:
A subject/guardian may terminate participation in the study at any time without necessarily giving a reason and without any personal disadvantage. An investigator can stop the participation of a subject after consideration of the benefit/risk ratio. Possible reasons are:
- Serious adverse events
- Non-compliance
- Serious protocol violation
- Decision by the investigator, or the sponsor, that termination is in the subject's best medical interest
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Closed loop with diluted insulin | Experimental | Device: FlorenceMUnsupervised 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. |
| Closed loop with standard insulin strength | Active comparator | Device: FlorenceMUnsupervised 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. |
Who may qualify
- Ages
- 1 year to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- Age between 1 and 7 years of age (inclusive)
- Type 1 diabetes as defined by WHO for at least 6 months
- 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
- Treated with rapid acting insulin analogue insulin Aspart (Novo Nordisk, Bagsvaerd, Denmark)
- Subject/carer is willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements taken every day
Key exclusion criteria (15 listed)
- 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
- Untreated coeliac disease or thyroid disease based on local investigations prior to study enrolment
- Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids
- Known or suspected allergy to insulin
- 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]
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FlorenceMThe 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. | Device | Closed loop with diluted insulin, Closed loop with standard insulin strength |
Primary outcome
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)
12 secondary outcomes
Time spent below target glucose (3.9mmol/l)(70mg/dl)
Time frame: 3-week home stay
Time spent above target glucose (10.0mmol/l) (180mg/dl)
Time frame: 3-week home stay
Average glucose
Time frame: 3-week home stay
Standard deviation of glucose levels
Time frame: 3-week home stay
Coefficient of variation of glucose levels
Time frame: 3-week home stay
Time with glucose levels < 3.5mmol/l (63 mg/dl)
Time frame: 3-week home stay
Time with glucose levels <2.8mmol/l (50mg/dl)
Time frame: 3-week home stay
Time with glucose levels in significant hyperglycaemia
Time frame: 3-week home stay
Total daily insulin dose
Time frame: 3-week home stay
Daily basal insulin dose
Time frame: 3-week home stay
Daily bolus insulin dose
Time frame: 3-week home stay
AUC of glucose below 3.5mmol/l (63mg/dl)
Time frame: 3-week home stay
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2018.
- Background: PubMed 25512874Elleri D, Allen JM, Tauschmann M, El-Khairi R, Benitez-Aguirre P, Acerini CL, Dunger DB, Hovorka R. Feasibility of overnight closed-loop therapy in young children with type 1 diabetes aged 3-6 years: comparison between diluted and standard insulin strength. BMJ Open Diabetes Res Care. 2014 Dec 11;2(1):e000040. doi: 10.1136/bmjdrc-2014-000040. eCollection 2014.
- Background: PubMed 25537835Ruan Y, Elleri D, Allen JM, Tauschmann M, Wilinska ME, Dunger DB, Hovorka R. Pharmacokinetics of diluted (U20) insulin aspart compared with standard (U100) in children aged 3-6 years with type 1 diabetes during closed-loop insulin delivery: a randomised clinical trial. Diabetologia. 2015 Apr;58(4):687-90. doi: 10.1007/s00125-014-3483-6. Epub 2014 Dec 24.
- Background: PubMed 26379095Thabit H, Tauschmann M, Allen JM, Leelarathna L, Hartnell S, Wilinska ME, Acerini CL, Dellweg S, Benesch C, Heinemann L, Mader JK, Holzer M, Kojzar H, Exall J, Yong J, Pichierri J, Barnard KD, Kollman C, Cheng P, Hindmarsh PC, Campbell FM, Arnolds S, Pieber TR, Evans ML, Dunger DB, Hovorka R; New Collective Author. Home Use of an Artificial Beta Cell in Type 1 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2129-2140. doi: 10.1056/NEJMoa1509351. Epub 2015 Sep 17.
- Background: PubMed 26740634Tauschmann M, Allen JM, Wilinska ME, Thabit H, Stewart Z, Cheng P, Kollman C, Acerini CL, Dunger DB, Hovorka R. Day-and-Night Hybrid Closed-Loop Insulin Delivery in Adolescents With Type 1 Diabetes: A Free-Living, Randomized Clinical Trial. Diabetes Care. 2016 Jul;39(7):1168-74. doi: 10.2337/dc15-2078. Epub 2016 Jan 6.
- Background: PubMed 27612500Tauschmann M, Allen JM, Wilinska ME, Thabit H, Acerini CL, Dunger DB, Hovorka R. Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Suboptimally Controlled Adolescents With Type 1 Diabetes: A 3-Week, Free-Living, Randomized Crossover Trial. Diabetes Care. 2016 Nov;39(11):2019-2025. doi: 10.2337/dc16-1094. Epub 2016 Sep 9.
- Derived from this study: PubMed 30692242Tauschmann M, Allen JM, Nagl K, Fritsch M, Yong J, Metcalfe E, Schaeffer D, Fichelle M, Schierloh U, Thiele AG, Abt D, Kojzar H, Mader JK, Slegtenhorst S, Barber N, Wilinska ME, Boughton C, Musolino G, Sibayan J, Cohen N, Kollman C, Hofer SE, Frohlich-Reiterer E, Kapellen TM, Acerini CL, de Beaufort C, Campbell F, Rami-Merhar B, Hovorka R; KidsAP Consortium. Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Very Young Children: A Multicenter, 3-Week, Randomized Trial. Diabetes Care. 2019 Apr;42(4):594-600. doi: 10.2337/dc18-1881. Epub 2019 Jan 28.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roman Hovorka, PhD study director
Department of Paediatrics, University of Cambridge, UK
Carlo Acerini, MD principal investigator
Department of Paediatrics, University of Cambridge, UK
Carine de Beaufort, PhD principal investigator
Clinique Pédiatrique de Luxembourg, University of Luxembourg, Luxembourg
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing FlorenceM in people with Type 1 Diabetes Mellitus, run by University of Cambridge at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Austria, United Kingdom, Germany, Luxembourg. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time in target (3.9 to 10.0mmol/l) (70 to 180 mg/dl) (time frame: 3-week home stay). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03101865, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2018.