FASter Insulin in Closed-loop Technology in Children
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional

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.

      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.

        1. 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.

        2. 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.

        3. UTILITY: The objective is to determine the acceptability and duration of use of the
           closed-loop system.

        4. 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:

        1. Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge

        2. John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford

        3. Nottingham Children's Hospital, Nottingham

        4. 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.

        1. 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.

        2. 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:

        1. Serious adverse events

        2. Serious protocol violation

        3. Non-compliance

        4. Failure to satisfy competency assessment

        5. Decision by the investigator, or the Sponsor, that termination is in the participant's
           best medical interest

        6. Allergic reaction to insulin
    

Intervention name(s): CamAPS FX using faster insulin aspart; CamAPS FX using standard insulin aspart
Intervention type(s): Device; Device
Intervention description(s): 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 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
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention 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 (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Faster insulin aspart; Closed loop insulin delivery