Type 1 Diabetes MellitusFAST-KidsNCT04759144
FASter Insulin in Closed-loop Technology in Children
A study testing CamAPS FX using faster insulin aspart and CamAPS FX using standard insulin aspart in people with Type 1 Diabetes Mellitus, run by University of Cambridge at 2 sites in United Kingdom.
Trial summary
The main objective of this study is to determine whether 24/7 hybrid closed-loop insulin delivery under free living conditions applying faster insulin aspart (FiAsp) is superior to 24/7 hybrid closed-loop insulin delivery applying standard insulin aspart in very young children with type 1 diabetes. Read more about this study
- Who is it for?
- Ages 2 to 6 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- CamAPS FX using faster insulin aspart and CamAPS FX using standard insulin aspart
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 12 Mar 2021to 1 Dec 2022
- 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 2 to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age between 2 and 6 years (inclusive)
- Type 1 diabetes as defined by WHO for at least 6 months [WHO definition: 'The aetiological type named type 1 encompasses the majority of cases which are primarily due to beta-cell destruction, and are prone to ketoacidosis. Type 1 includes those cases attributable to an autoimmune process, as well as those with beta-cell destruction for which neither an aetiology nor a pathogenesis is known (idiopathic). It does not include those forms of beta-cell destruction or failure to which specific causes can be assigned (e.g. cystic fibrosis, mitochondrial defects, etc.).']
- Insulin pump user (with or without continuous glucose monitoring or flash glucose monitoring system) for at least 3 months, with parent/guardian good knowledge of insulin self-adjustment as judged by the investigator
- Treated with U-100 rapid or ultra-rapid acting insulin analogue
- Screening HbA1c ≤ 11% (97mmol/mol) on analysis from local laboratory
- Able to wear glucose sensor
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- Able to wear closed-loop system 24/7
- The parent/guardian is willing to follow study specific instructions
- The parent/guardian is proficient in English
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
- Parent/guardian's lack of reliable telephone facility for contact
- Parent/guardian's severe visual impairment
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- Parent/guardian'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)
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
University Department of Paediatrics
Cambridge, Cambridgeshire, CB2 0QQ
Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge
Cambridge, Cambridgeshire, CB2 0QQ
About this study
Official title: A Randomised Crossover Study Comparing Hybrid Closed-loop Insulin Delivery Using Ultra-rapid Acting Insulin to Hybrid Closed-loop Insulin Delivery Using Standard Rapid-acting Insulin in Children With Type 1 Diabetes in the Home Setting (FAST-Kids)
The main objective of this study is to determine whether 24/7 hybrid closed-loop insulin delivery under free living conditions applying faster insulin aspart (FiAsp) is superior to 24/7 hybrid closed-loop insulin delivery applying standard insulin aspart in very young children with type 1 diabetes.
The closed-loop system consists of three components: the continuous glucose monitor (CGM), the insulin pump and a smartphone Application, or App, that translates, in real-time, sensor glucose levels received from the glucose monitoring device and calculates the amount of insulin to be delivered by the coupled insulin pump.
Read more
This is a double-blind, multi-centre, randomised, crossover design study, involving a run-in period followed by two 8-week study periods during which glucose levels will be controlled by a hybrid closed-loop system using either standard insulin aspart or faster insulin aspart in random order.
Participants aged 2-6 years with type 1 diabetes on insulin pump therapy will be recruited through paediatric diabetes outpatient clinics at participating clinical centres. Enrolment will target up to 30 children (aiming for 6-14 participants per centre) to allow for dropouts during run-in.
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 CGM device, and the hybrid closed-loop insulin delivery system. Parents/guardians at nursey/school may also receive training by the study team if required. Participants will have regular contact with the study team during the study including 24/7 telephone support. Parents/guardians will be asked to complete validated questionnaires at the start and end of the study to assess quality of life measures including sleep.
The primary outcome is the between group difference in time spent in target range between 3.9 and 10.0 mmol/l as recorded by CGM during the study. Secondary outcomes are time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises assessment of the frequency and severity of hypoglycaemic episodes and diabetic ketoacidosis (DKA).
Read the detailed description
Purpose of clinical trial:
To compare hybrid closed-loop applying faster insulin aspart to hybrid closed-loop applying standard insulin aspart over 8 weeks.
Study objectives:
The study objective is to compare hybrid closed-loop glucose control using faster insulin aspart with hybrid closed-loop control using standard insulin aspart in very young children with type 1 diabetes.
- EFFICACY: The objective is to assess the ability of a hybrid closed-loop system applying faster insulin aspart to maintain CGM glucose levels within the target range from 3.9 to 10.0 mmol/l, in comparison to a hybrid closed-loop system applying standard insulin aspart in very young children with type 1 diabetes.
- SAFETY: The objective is to evaluate the safety of closed-loop glucose control using faster insulin aspart compared to standard insulin aspart in terms of episodes and severity of hypoglycaemia, frequency of diabetic ketoacidosis (DKA) and nature and severity of other adverse events.
- UTILITY: The objective is to determine the acceptability and duration of use of the closed-loop system.
- HUMAN FACTORS: The objective is to assess emotional and behavioural characteristics of parents/guardians and their response to the closed-loop system and clinical trial using validated surveys.
Participating clinical centres:
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
- John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford
- Nottingham Children's Hospital, Nottingham
- Alder Hey Children's Hospital, Liverpool
Sample Size:
24 children randomised (6-14 participants per centre).
Maximum duration of study for a subject:
6 months
Recruitment:
Participants will be recruited through the paediatric diabetes outpatient clinics at participating clinical centres (see above). Enrolment will target up to 30 participants (aiming for 6-14 participants per centre), to allow for dropouts during run-in.
Consent:
Written informed consent will be obtained from all parents/guardians.
Screening and baseline Assessment:
Eligible participants will undergo a baseline assessment including a blood sample for the measurement of HbA1c. Height and weight will be recorded. Validated questionnaires will be completed by parents/guardians.
Pre-Study Training and Run-in:
Training sessions on the use of the study CGM, insulin pump and hybrid closed-loop insulin delivery will be provided by the research team. During the closed-loop training session, parents/guardians will operate the system under the supervision of the clinical research team. Participants and parents/guardians will use the study CGM, insulin pump, and hybrid closed-loop insulin delivery during a 2-4 week run-in period. For compliance and to assess the ability of the participant to use the study devices safely, at least 8 days of CGM data need to be recorded and safe use of study insulin pump and hybrid closed-loop insulin delivery demonstrated during the last 14 days of the run-in period. The CGM data will also be used to assess baseline glucose control and may be used for treatment optimisation as necessary.
Competency Assessment:
Competency on the use of study pump,study CGM and hybrid closed-loop insulin delivery will be evaluated by the research team. Training may be repeated if required.
Randomisation:
Eligible participants will be randomised using randomisation software to the initial use of faster insulin aspart with the hybrid closed-loop system or to standard insulin aspart with the hybrid closed-loop system for 8 weeks before crossing over to the other treatment arm.
- Faster insulin aspart with hybrid closed-loop: Participants and their parents/guardians will use the hybrid closed-loop system with faster insulin aspart for 8 weeks at home. The participant, parents/guardians and the research team will be blinded to the intervention. Crossover assessment: At the end of the first study arm, validated questionnaires will be completed by the parents/guardians.
- Standard insulin aspart with hybrid closed-loop:
Participants and their parents/guardians will use the hybrid closed-loop system with standard insulin aspart for 8 weeks at home. The participant, parents/guardians and the research team will be blinded to the intervention.
Study contacts:
Participants and parents/guardians will be contacted 24 hours after starting each study arm to ensure there are no concerns regarding the study devices. Participants will be contacted by the study team (email/phone) 2 and 4 weeks after the start of each study arm in order to record any adverse events, device deficiencies, and changes in insulin settings, other medical conditions and/or medication.
In case of any problems related to the technical devices or diabetes management, participants and parents/guardians will be able to contact a 24-hour telephone helpline to the local research team. The local research team will have access to central 24 hour advice on technical issues.
End of study assessments:
Height and weight will be recorded. Validated questionnaires will be completed by parents/guardians. Participants will resume usual care using their pre-study insulin pump.
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), serious adverse device effects (SADE) and specific adverse events (AE) such as severe hypoglycaemia.
A data safety and monitoring board (DSMB) will be informed of all serious adverse events and any unanticipated serious adverse device effects that occur during the study and will review compiled adverse event data at periodic intervals.
Criteria for withdrawal of subjects on safety grounds:
A participant and parent/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 participant after consideration of the benefit/risk ratio. Possible reasons are:
- Serious adverse events
- Serious protocol violation
- Non-compliance
- Failure to satisfy competency assessment
- Decision by the investigator, or the Sponsor, that termination is in the participant's best medical interest
- Allergic reaction to insulin
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- CamAPS FX using faster insulin aspart, CamAPS FX using standard insulin aspart
- Keywords
- Faster insulin aspart, Closed loop insulin delivery
- 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.
CamAPS FX using faster insulin aspartDevice
CamAPS FX closed loop system comprises:
- Dana insulin pump (Diabecare, Sooil, Seoul, South Korea)
- Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA)
- An Android smartphone hosting CamAPS FX app with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump and glucose sensor
- Cloud upload system to monitor CGM/insulin data
CamAPS FX using standard insulin aspartDevice
CamAPS FX closed loop system comprises:
- Dana insulin pump (Diabecare, Sooil, Seoul, South Korea)
- Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA)
- An Android smartphone hosting CamAPS FX app with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump and glucose sensor
- Cloud upload system to monitor CGM/insulin data
| Study group | Role | What they receive |
|---|---|---|
| Faster insulin aspart with hybrid closed-loop insulin delivery | Active comparator | Unsupervised home use of hybrid closed-loop insulin delivery with faster insulin aspart for 8 weeks.
Intervention: Use of faster insulin aspart with hybrid closed-loop insulin delivery Receives: Device: CamAPS FX using faster insulin aspart |
| Standard insulin aspart with hybrid closed-loop insulin delivery | Active comparator | Unsupervised home use of hybrid closed-loop insulin delivery with standard insulin aspart for 8 weeks.
Intervention: Use of standard insulin aspart with hybrid closed-loop insulin delivery Receives: Device: CamAPS FX using standard insulin aspart |
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)
Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM)
Measured: 8-week intervention
Secondary outcomes (15)
Time spent above target glucose (10.0 mmol/L) (180 mg/dL)
Percentage of time spent with sensor glucose readings above target glucose (10.0mmol/L) (180mg/dL)
Measured: 8-week intervention
Mean glucose
Average of sensor glucose levels
Measured: 8-week intervention
Time spent below target glucose (3.9 mmol/L) (70 mg/dL)
Percentage of time spent with sensor glucose readings below target glucose (3.9mmol/L)(70mg/dL)
Measured: 8-week intervention
Standard deviation of glucose
Standard deviation Standard deviation of sensor glucose levels
Measured: 8-week intervention
Coefficient of variation of glucose
Coefficient of variation of sensor glucose levels
Measured: 8-week intervention
Time spent below target glucose (3.0 mmol/L) (54 mg/dL)
Percentage of time spent with sensor glucose readings below target glucose (3.0mmol/L)(54mg/dL)
Measured: 8-week intervention
Time with glucose levels in significant hyperglycaemia (glucose levels > 16.7 mmol/L) (300 mg/dL)
Percentage of time spent with glucose levels in significant hyperglycaemia (glucose levels > 16.7mmol/L) (300mg/dL)
Measured: 8-week intervention
BMI SDS
Measured: 8-week intervention
Total, basal, and bolus insulin dose
Measured: 8-week intervention
Number of episodes of severe hypoglycaemia
Safety evaluation
Measured: Through study completion, an average of 5 months
Frequency of diabetic ketoacidosis
Safety evaluation
Measured: Through study completion, an average of 5 months
Frequency and nature of other adverse events or serious adverse events
Safety evaluation
Measured: Through study completion, an average of 5 months
Closed-loop use
Percentage of time of closed-loop is operational (Utility evaluation)
Measured: Through study completion, an average of 5 months
CGM use
Percentage of time CGM is available (Utility evaluation)
Measured: Through study completion, an average of 5 months
Human factors assessment
Assessment of emotional and behavioural characteristics of parents/guardians, their response to the closed-loop system and information about parent/guardian sleep will be assessed through validated surveys.
Measured: 8-week intervention and 8-week control period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start12 Mar 2021
- Primary completion14 Sep 2022
- Study completion1 Dec 2022
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Device: CamAPS FX The automated closed loop system (CamAPS FX) will consist of: * Dana insulin pump (Diabecare, Sooil, Seoul, South Korea) * Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) * An Android smartphone hosting CamAPS FX app with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump and glucose sensor * Cloud upload system to monitor CGM/insulin data. Treatment: Two insulins will be used * Faster insulin aspart (Fiasp) * Standard insulin aspart (Novorapid)
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, Oxford University Hospitals NHS Trust, Nottingham University Hospitals NHS Trust, Alder Hey Children's NHS Foundation Trust
- Responsible party
- Principal investigator, Dr Roman Hovorka, University of Cambridge
- Investigators
- Roman Hovorka, PhD, Study director, Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04759144
- Sponsor's protocol ID
- FAST-Kids
- Acronym
- FAST-Kids
- Status last verified
- Mar 2023
- First submitted
- 13 Feb 2021
- Last updated
- 14 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication. To gain access, data requestors will need to sign a data access agreement. 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
Tauschmann M, Thabit H, Bally L, Allen JM, Hartnell S, Wilinska ME, Ruan Y, Sibayan J, Kollman C, Cheng P, Beck RW, Acerini CL, Evans ML, Dunger DB, Elleri D, Campbell F, Bergenstal RM, Criego A, Shah VN, Leelarathna L, Hovorka R; APCam11 Consortium. Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a multicentre, 12-week randomised trial. Lancet. 2018 Oct 13;392(10155):1321-1329. doi: 10.1016/S0140-6736(18)31947-0. Epub 2018 Oct 3.
PubMed 30292578Tauschmann 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 30692242Tauschmann 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 27612500Dovc K, Boughton C, Tauschmann M, Thabit H, Bally L, Allen JM, Acerini CL, Arnolds S, de Beaufort C, Bergenstal RM, Campbell F, Criego A, Dunger DB, Elleri D, Evans ML, Frohlich-Reiterer E, Hofer S, Kapellen T, Leelarathna L, Pieber TR, Rami-Merhar B, Shah VN, Sibayan J, Wilinska ME, Hovorka R; APCam11, AP@Home, and KidsAP Consortia. Young Children Have Higher Variability of Insulin Requirements: Observations During Hybrid Closed-Loop Insulin Delivery. Diabetes Care. 2019 Jul;42(7):1344-1347. doi: 10.2337/dc18-2625. Epub 2019 May 21.
PubMed 31221700Musolino G, Dovc K, Boughton CK, Tauschmann 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, Ashcroft N, Wilinska ME, 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. Reduced burden of diabetes and improved quality of life: Experiences from unrestricted day-and-night hybrid closed-loop use in very young children with type 1 diabetes. Pediatr Diabetes. 2019 Sep;20(6):794-799. doi: 10.1111/pedi.12872. Epub 2019 Jun 13.
PubMed 31140654Ware J, Allen JM, Boughton CK, Cezar A, Hartnell S, Wilinska ME, Thankamony A, Deakin M, Leyland H, Phelan K, Thornborough K, Hovorka R. Hybrid Closed-Loop with Faster Insulin Aspart Compared with Standard Insulin Aspart in Very Young Children with Type 1 Diabetes: A Double-Blind, Multicenter, Randomized, Crossover Study. Diabetes Technol Ther. 2023 Jun;25(6):431-436. doi: 10.1089/dia.2023.0042.
PubMed 36880866
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Crossover Study Comparing Hybrid Closed-loop Insulin Delivery Using Ultra-rapid Acting Insulin to Hybrid Closed-loop Insulin Delivery Using Standard Rapid-acting Insulin in Children With Type 1 Diabetes in the Home Setting (FAST-Kids)
- ClinicalTrials.gov ID
- NCT04759144
- Acronym / sponsor ID
- FAST-Kids / FAST-Kids
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Faster insulin aspart, Closed loop insulin delivery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, Oxford University Hospitals NHS Trust, Nottingham University Hospitals NHS Trust, Alder Hey Children's NHS Foundation Trust
- Study start
- 12 Mar 2021 (actual)
- Primary completion
- 14 Sep 2022 (actual)
- Study completion
- 1 Dec 2022 (actual)
- First posted
- 18 Feb 2021 (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 main objective of this study is to determine whether 24/7 hybrid closed-loop insulin delivery under free living conditions applying faster insulin aspart (FiAsp) is superior to 24/7 hybrid closed-loop insulin delivery applying standard insulin aspart in very young children with type 1 diabetes.
The closed-loop system consists of three components: the continuous glucose monitor (CGM), the insulin pump and a smartphone Application, or App, that translates, in real-time, sensor glucose levels received from the glucose monitoring device and calculates the amount of insulin to be delivered by the coupled insulin pump.
This is a double-blind, multi-centre, randomised, crossover design study, involving a run-in period followed by two 8-week study periods during which glucose levels will be controlled by a hybrid closed-loop system using either standard insulin aspart or faster insulin aspart in random order.
Participants aged 2-6 years with type 1 diabetes on insulin pump therapy will be recruited through paediatric diabetes outpatient clinics at participating clinical centres. Enrolment will target up to 30 children (aiming for 6-14 participants per centre) to allow for dropouts during run-in.
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 CGM device, and the hybrid closed-loop insulin delivery system. Parents/guardians at nursey/school may also receive training by the study team if required. Participants will have regular contact with the study team during the study including 24/7 telephone support. Parents/guardians will be asked to complete validated questionnaires at the start and end of the study to assess quality of life measures including sleep.
The primary outcome is the between group difference in time spent in target range between 3.9 and 10.0 mmol/l as recorded by CGM during the study. Secondary outcomes are time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises assessment of the frequency and severity of hypoglycaemic episodes and diabetic ketoacidosis (DKA).
Detailed description
Purpose of clinical trial:
To compare hybrid closed-loop applying faster insulin aspart to hybrid closed-loop applying standard insulin aspart over 8 weeks.
Study objectives:
The study objective is to compare hybrid closed-loop glucose control using faster insulin aspart with hybrid closed-loop control using standard insulin aspart in very young children with type 1 diabetes.
- EFFICACY: The objective is to assess the ability of a hybrid closed-loop system applying faster insulin aspart to maintain CGM glucose levels within the target range from 3.9 to 10.0 mmol/l, in comparison to a hybrid closed-loop system applying standard insulin aspart in very young children with type 1 diabetes.
- SAFETY: The objective is to evaluate the safety of closed-loop glucose control using faster insulin aspart compared to standard insulin aspart in terms of episodes and severity of hypoglycaemia, frequency of diabetic ketoacidosis (DKA) and nature and severity of other adverse events.
- UTILITY: The objective is to determine the acceptability and duration of use of the closed-loop system.
- HUMAN FACTORS: The objective is to assess emotional and behavioural characteristics of parents/guardians and their response to the closed-loop system and clinical trial using validated surveys.
Participating clinical centres:
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
- John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford
- Nottingham Children's Hospital, Nottingham
- Alder Hey Children's Hospital, Liverpool
Sample Size:
24 children randomised (6-14 participants per centre).
Maximum duration of study for a subject:
6 months
Recruitment:
Participants will be recruited through the paediatric diabetes outpatient clinics at participating clinical centres (see above). Enrolment will target up to 30 participants (aiming for 6-14 participants per centre), to allow for dropouts during run-in.
Consent:
Written informed consent will be obtained from all parents/guardians.
Screening and baseline Assessment:
Eligible participants will undergo a baseline assessment including a blood sample for the measurement of HbA1c. Height and weight will be recorded. Validated questionnaires will be completed by parents/guardians.
Pre-Study Training and Run-in:
Training sessions on the use of the study CGM, insulin pump and hybrid closed-loop insulin delivery will be provided by the research team. During the closed-loop training session, parents/guardians will operate the system under the supervision of the clinical research team. Participants and parents/guardians will use the study CGM, insulin pump, and hybrid closed-loop insulin delivery during a 2-4 week run-in period. For compliance and to assess the ability of the participant to use the study devices safely, at least 8 days of CGM data need to be recorded and safe use of study insulin pump and hybrid closed-loop insulin delivery demonstrated during the last 14 days of the run-in period. The CGM data will also be used to assess baseline glucose control and may be used for treatment optimisation as necessary.
Competency Assessment:
Competency on the use of study pump,study CGM and hybrid closed-loop insulin delivery will be evaluated by the research team. Training may be repeated if required.
Randomisation:
Eligible participants will be randomised using randomisation software to the initial use of faster insulin aspart with the hybrid closed-loop system or to standard insulin aspart with the hybrid closed-loop system for 8 weeks before crossing over to the other treatment arm.
- Faster insulin aspart with hybrid closed-loop: Participants and their parents/guardians will use the hybrid closed-loop system with faster insulin aspart for 8 weeks at home. The participant, parents/guardians and the research team will be blinded to the intervention. Crossover assessment: At the end of the first study arm, validated questionnaires will be completed by the parents/guardians.
- Standard insulin aspart with hybrid closed-loop:
Participants and their parents/guardians will use the hybrid closed-loop system with standard insulin aspart for 8 weeks at home. The participant, parents/guardians and the research team will be blinded to the intervention.
Study contacts:
Participants and parents/guardians will be contacted 24 hours after starting each study arm to ensure there are no concerns regarding the study devices. Participants will be contacted by the study team (email/phone) 2 and 4 weeks after the start of each study arm in order to record any adverse events, device deficiencies, and changes in insulin settings, other medical conditions and/or medication.
In case of any problems related to the technical devices or diabetes management, participants and parents/guardians will be able to contact a 24-hour telephone helpline to the local research team. The local research team will have access to central 24 hour advice on technical issues.
End of study assessments:
Height and weight will be recorded. Validated questionnaires will be completed by parents/guardians. Participants will resume usual care using their pre-study insulin pump.
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), serious adverse device effects (SADE) and specific adverse events (AE) such as severe hypoglycaemia.
A data safety and monitoring board (DSMB) will be informed of all serious adverse events and any unanticipated serious adverse device effects that occur during the study and will review compiled adverse event data at periodic intervals.
Criteria for withdrawal of subjects on safety grounds:
A participant and parent/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 participant after consideration of the benefit/risk ratio. Possible reasons are:
- Serious adverse events
- Serious protocol violation
- Non-compliance
- Failure to satisfy competency assessment
- Decision by the investigator, or the Sponsor, that termination is in the participant's best medical interest
- Allergic reaction to insulin
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Device: CamAPS FX The automated closed loop system (CamAPS FX) will consist of: * Dana insulin pump (Diabecare, Sooil, Seoul, South Korea) * Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) * An Android smartphone hosting CamAPS FX app with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump and glucose sensor * Cloud upload system to monitor CGM/insulin data. Treatment: Two insulins will be used * Faster insulin aspart (Fiasp) * Standard insulin aspart (Novorapid)
| Arm | Type | Receives |
|---|---|---|
| Faster insulin aspart with hybrid closed-loop insulin delivery | Active comparator | Device: CamAPS FX using faster insulin aspartUnsupervised home use of hybrid closed-loop insulin delivery with faster insulin aspart for 8 weeks. Intervention: Use of faster insulin aspart with hybrid closed-loop insulin delivery |
| Standard insulin aspart with hybrid closed-loop insulin delivery | Active comparator | Device: CamAPS FX using standard insulin aspartUnsupervised home use of hybrid closed-loop insulin delivery with standard insulin aspart for 8 weeks. Intervention: Use of standard insulin aspart with hybrid closed-loop insulin delivery |
Who may qualify
- Ages
- 2 to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Age between 2 and 6 years (inclusive)
- Type 1 diabetes as defined by WHO for at least 6 months [WHO definition: 'The aetiological type named type 1 encompasses the majority of cases which are primarily due to beta-cell destruction, and are prone to ketoacidosis. Type 1 includes those cases attributable to an autoimmune process, as well as those with beta-cell destruction for which neither an aetiology nor a pathogenesis is known (idiopathic). It does not include those forms of beta-cell destruction or failure to which specific causes can be assigned (e.g. cystic fibrosis, mitochondrial defects, etc.).']
- Insulin pump user (with or without continuous glucose monitoring or flash glucose monitoring system) for at least 3 months, with parent/guardian good knowledge of insulin self-adjustment as judged by the investigator
- Treated with U-100 rapid or ultra-rapid acting insulin analogue
- Screening HbA1c ≤ 11% (97mmol/mol) on analysis from local laboratory
Key exclusion criteria (9 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
- Parent/guardian's lack of reliable telephone facility for contact
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 |
|---|---|---|
| CamAPS FX using faster insulin aspartCamAPS FX closed loop system comprises: * Dana insulin pump (Diabecare, Sooil, Seoul, South Korea) * Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) * An Android smartphone hosting CamAPS FX app with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump and glucose sensor * Cloud upload system to monitor CGM/insulin data | Device | Faster insulin aspart with hybrid closed-loop insulin delivery |
| CamAPS FX using standard insulin aspartCamAPS FX closed loop system comprises: * Dana insulin pump (Diabecare, Sooil, Seoul, South Korea) * Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) * An Android smartphone hosting CamAPS FX app with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump and glucose sensor * Cloud upload system to monitor CGM/insulin data | Device | Standard insulin aspart with hybrid closed-loop insulin delivery |
Primary outcome
Time in target (3.9 to 10.0mmol/L) (70 to 180 mg/dL)
Time frame: 8-week intervention
Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM)
15 secondary outcomes
Time spent above target glucose (10.0 mmol/L) (180 mg/dL)
Time frame: 8-week intervention
Mean glucose
Time frame: 8-week intervention
Time spent below target glucose (3.9 mmol/L) (70 mg/dL)
Time frame: 8-week intervention
Standard deviation of glucose
Time frame: 8-week intervention
Coefficient of variation of glucose
Time frame: 8-week intervention
Time spent below target glucose (3.0 mmol/L) (54 mg/dL)
Time frame: 8-week intervention
Time with glucose levels in significant hyperglycaemia (glucose levels > 16.7 mmol/L) (300 mg/dL)
Time frame: 8-week intervention
BMI SDS
Time frame: 8-week intervention
Total, basal, and bolus insulin dose
Time frame: 8-week intervention
Number of episodes of severe hypoglycaemia
Time frame: Through study completion, an average of 5 months
Frequency of diabetic ketoacidosis
Time frame: Through study completion, an average of 5 months
Frequency and nature of other adverse events or serious adverse events
Time frame: Through study completion, an average of 5 months
Closed-loop use
Time frame: Through study completion, an average of 5 months
CGM use
Time frame: Through study completion, an average of 5 months
Human factors assessment
Time frame: 8-week intervention and 8-week control period
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 14 Mar 2023.
- Background: PubMed 30292578Tauschmann M, Thabit H, Bally L, Allen JM, Hartnell S, Wilinska ME, Ruan Y, Sibayan J, Kollman C, Cheng P, Beck RW, Acerini CL, Evans ML, Dunger DB, Elleri D, Campbell F, Bergenstal RM, Criego A, Shah VN, Leelarathna L, Hovorka R; APCam11 Consortium. Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a multicentre, 12-week randomised trial. Lancet. 2018 Oct 13;392(10155):1321-1329. doi: 10.1016/S0140-6736(18)31947-0. Epub 2018 Oct 3.
- Background: 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.
- 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.
- Background: PubMed 31221700Dovc K, Boughton C, Tauschmann M, Thabit H, Bally L, Allen JM, Acerini CL, Arnolds S, de Beaufort C, Bergenstal RM, Campbell F, Criego A, Dunger DB, Elleri D, Evans ML, Frohlich-Reiterer E, Hofer S, Kapellen T, Leelarathna L, Pieber TR, Rami-Merhar B, Shah VN, Sibayan J, Wilinska ME, Hovorka R; APCam11, AP@Home, and KidsAP Consortia. Young Children Have Higher Variability of Insulin Requirements: Observations During Hybrid Closed-Loop Insulin Delivery. Diabetes Care. 2019 Jul;42(7):1344-1347. doi: 10.2337/dc18-2625. Epub 2019 May 21.
- Background: PubMed 31140654Musolino G, Dovc K, Boughton CK, Tauschmann 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, Ashcroft N, Wilinska ME, 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. Reduced burden of diabetes and improved quality of life: Experiences from unrestricted day-and-night hybrid closed-loop use in very young children with type 1 diabetes. Pediatr Diabetes. 2019 Sep;20(6):794-799. doi: 10.1111/pedi.12872. Epub 2019 Jun 13.
- Derived from this study: PubMed 36880866Ware J, Allen JM, Boughton CK, Cezar A, Hartnell S, Wilinska ME, Thankamony A, Deakin M, Leyland H, Phelan K, Thornborough K, Hovorka R. Hybrid Closed-Loop with Faster Insulin Aspart Compared with Standard Insulin Aspart in Very Young Children with Type 1 Diabetes: A Double-Blind, Multicenter, Randomized, Crossover Study. Diabetes Technol Ther. 2023 Jun;25(6):431-436. doi: 10.1089/dia.2023.0042.
- Individual participant dataSharing planned: Yes. Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication. To gain access, data requestors will need to sign a data access agreement. 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
Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CamAPS FX using faster insulin aspart and CamAPS FX using standard insulin aspart in people with Type 1 Diabetes Mellitus, run by University of Cambridge at 2 sites in United Kingdom.
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 9 inclusion and 9 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 14 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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: 8-week intervention). 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 NCT04759144, 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 14 Mar 2023.