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CompletedNCT03784027KidsAP02Updated Mar 27, 2025Results posted

The Artificial Pancreas in Very Young Children With T1D

An interventional study of CamAPS FX and Sensor augmented therapy in Type 1 Diabetes Mellitus, sponsored by University of Cambridge. Completed at 8 sites in 4 countries. Open to participants aged 1 Year to 7 Years. Per ClinicalTrials.gov, last updated 2025-03-27.

Sponsored by University of Cambridge · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
81
Allocation
Randomized
Ages
1 Year to 7 Years
Sex
All
01

Study summary

The suggested clinical trial is part of the KidsAP project funded by the European Commission's Horizon 2020 Framework Programme and JDRF. It evaluates the use of the Artificial Pancreas (closed loop system) in very young children with type 1 diabetes (T1D) aged 1-7 years. This outcome study aims to determine whether 24/7 automated closed loop glucose control improves time in range compared to sensor augmented pump therapy. An extension phase will evaluate the effect of long-term home use of the 24/7 automated hybrid closed loop insulin delivery system on glucose control (UK sites only).

The study employs an open-label, multi-centre, multi-national, randomized, two-period, crossover design. Participants undergo a 2-4 week run-in period, followed by two 16-week treatment periods (one for each therapy) separated by a 1-4 week washout. The order of treatments is randomized. Up to 80 young children (with a target of 72 randomized subjects) on insulin pump therapy will be recruited from paediatric outpatient diabetes clinics.

Before using the study devices, participants and their parents/guardians receive training on the safe use of the study pump, continuous glucose monitoring (CGM) device, and hybrid closed loop system. Nursery or school carers may also be trained if needed. During the closed loop arm, subjects use the system for 16 weeks under free-living conditions at home and in nursery/school without remote monitoring. In the control arm, subjects use sensor augmented pump therapy for 16 weeks under similar conditions, with regular contact and 24/7 telephone support from the study team.

The primary endpoint is the time spent in the target glucose range (3.9-10.0 mmol/l) as recorded by CGM. Secondary outcomes include the time spent with glucose levels above and below target and other CGM metrics. Safety assessments include the frequency and severity of hypoglycaemic episodes and diabetic ketoacidosis (DKA). In the extension phase, participants have follow-up contacts every 3 months, with the primary endpoint measured over 18 months from the end of the primary phase and compared to sensor augmented pump therapy during that phase. Secondary outcomes, safety, and utility will be assessed similarly.

Read the detailed description

Purpose of clinical trial:

To determine whether 24/7 automated hybrid closed loop will improve glucose control as measured by time within the target range compared with sensor augmented pump therapy in very young children with T1D.

Study objectives:

The study objective is to evaluate the safety, efficacy and utility of automated hybrid closed loop glucose control in very young children with type 1 diabetes.

  1. EFFICACY: The objective is to assess the ability of a hybrid closed loop system to maintain CGM glucose levels within the target range of 3.9 to 10 mmol/l (70 to 180 mg/dl) in comparison with sensor augmented pump therapy in very young children with type 1 diabetes.
  2. SAFETY: The objective is to evaluate the safety of closed loop glucose control compared with sensor augmented pump therapy 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 in this population.
  4. HUMAN FACTORS: The objective is to assess emotional and behavioural characteristics of participants and parents/guardians and their response to the closed loop system and clinical trial using validated surveys and semi-structured qualitative interviews.
  5. HEALTH ECONOMICS: The objective is to perform a cost utility analysis to inform reimbursement decision-making.

Participating clinical centres:

  1. Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
  2. Leeds Teaching Hospitals NHS Trust, Leeds, UK
  3. DECCP, Centre Hospitalier de Luxembourg, Grand Duché de Luxembourg
  4. University of Leipzig, Leipzig, Germany
  5. Medical University of Graz, Graz, Austria
  6. Medical University of Innsbruck, Innsbruck, Austria
  7. Medical University of Vienna, Vienna, Austria

Sample Size:

72 participants randomised (8-12 participants per centre). At the primary phase final visit, participants (UK sites only) on sensor-augmented pump therapy as their standard clinical care will be invited to participate in an extension phase of closed loop therapy for a further 18 months.

Maximum duration of study for a subject: 11 months (primary phase). 29 months for participants (UK sites only) opting to participate in 18-month extension phase.

Recruitment:

The subjects will be recruited through paediatric diabetes outpatient clinics at participating clinical centres (see above). Enrolment will target up to 80 (aiming for 8-12 participants per centre) to allow for dropouts during run-in.

Participants (UK sites only) completing the primary phase, who are on sensor-augmented pump therapy as their standard clinical care, will be invited to participate in the extension phase.

Consent:

Written informed consent will be obtained from all parents/guardians and written assent from older children before any study related activities.

Additional written consent will be obtained for the extension phase from all parents/guardians.

Baseline Assessment:

Eligible subjects will undergo a baseline assessment 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 using randomisation software to the initial use of automated hybrid closed loop glucose system or to sensor augmented pump therapy for 16 weeks with a 1 to 4 week washout period before crossing over to the other study arm.

Automated day and night closed loop insulin delivery (intervention arm)

Participants in the closed loop arm and their caregivers will receive an additional training session covering the use of the closed loop system provided by the research team prior to starting closed loop insulin delivery. During this 1-2 hour session, parents/guardians will operate the system under the supervision of the clinical research team. Competency on the use of closed loop system will be evaluated. Thereafter, subjects and their parents/guardians will use the hybrid closed loop system for 16 weeks at home.

Crossover Assessment:

At the end of the first study arm, a blood sample for the measurement of HbA1c will be taken and weight and height will be measured. Validated surveys evaluating the impact of the devices employed on quality of life, psychosocial function, diabetes management and treatment satisfaction will be completed.

Parents/guardians will be invited to be interviewed to gather feedback on and reactions to their current treatment, the clinical trial, and quality of life changes.

Sensor augmented pump therapy (control arm):

Participants in the sensor augmented pump therapy arm and their caregivers will receive refresher training on key aspects of insulin pump therapy and CGM use.

Subjects and their parents/guardians will continue using sensor augmented pump therapy for 16 weeks at home.

Study contacts:

Participants will be contacted 24h after starting each study arm to ensure there are no concerns regarding the study devices. In between study visits, participants will be contacted by the study team (email/phone) once monthly and 3-monthly in the extension phase, 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 device or diabetes management such as hypo- or hyperglycaemia, subjects will be able to contact a 24-hour telephone helpline to the local research team at any time. The local research team will have access to central 24 hour advice on technical issues.

End of study assessments (primary phase):

A blood sample will be taken for measurement of HbA1c at the end of the study. Height and weight will be recorded. Study devices will be downloaded and returned. Participants will resume usual care using their pre-study insulin pump. Validated surveys evaluating the impact of the devices employed on quality of life, psychosocial function and diabetes management and treatment satisfaction will be completed.

Parents/guardians will be invited to participate in a sleep sub-study prior to the final visit (UK \& Luxembourg only).

Parents/guardians will be invited to be interviewed to gather feedback on and reactions to their current treatment, the clinical trial, and quality of life changes.

Extension Phase (UK sites only):

Follow up contacts will be conducted 3-monthly, in line with routine clinic visits, including recording of adverse events, medical history, insulin requirements and HbA1c.

After 18 months from the end of the primary phase, parents/guardians will complete validated questionnaires evaluating the impact of the technology on quality of life, diabetes management, sleep quality and fear of hypoglycaemia. Height and weight will be measured. A blood sample will be taken for measurement of HbA1c at the end of the extension phase

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 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
  • Allergic reaction to insulin
02

Conditions studied

  • Type 1 Diabetes Mellitus
03

Who can participate

Ages eligible
1 Year to 7 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Age between 1 and 7 years (inclusive) (Luxembourg and Austria)
  2. Age between 2 and 7 years (inclusive) (Germany and UK)
  3. 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.).']
  4. 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
  5. On sensor-augmented pump as standard clinical care (extension phase only)
  6. Treated with rapid or ultra-rapid acting insulin analogue
  7. Subject/carer is willing to perform regular finger-prick blood glucose monitoring, with at least 2 blood glucose measurements taken every day
  8. Screening HbA1c ≤ 11% (97mmol/mol) on analysis from local laboratory
  9. Willing to wear glucose sensor
  10. Willing to wear closed loop system 24/7 during intervention arm
  11. The subject/carer is willing to follow study specific instructions
  12. The subject/carer is willing to upload pump and CGM data at regular intervals

Exclusion criteria

Exclusion Criteria:

  1. Physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
  2. Untreated coeliac disease or thyroid disease based on local investigations prior to study enrolment
  3. Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids
  4. Use of closed loop insulin delivery within the past 2 months
  5. Known or suspected allergy to insulin
  6. Carer's lack of reliable telephone facility for contact
  7. Subject/carer's severe visual impairment
  8. Subject/carer's severe hearing impairment
  9. Medically documented allergy towards the adhesive (glue) of plasters or subject is unable to tolerate tape adhesive in the area of sensor placement
  10. 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)
  11. Sickle cell disease, haemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
  12. Plan to receive red blood cell transfusion or erythropoietin over the course of study participation

  13. Subject/carer not proficient in English (UK, Germany, Austria, Luxembourg) or German (Germany, Austria, Luxembourg) or French (Luxembourg)

    Additional exclusion criteria - Germany only

  14. Known microvascular diabetes complications (retinopathy, renal disease, neuropathy)
  15. Eating disorders
  16. Psychiatric diseases of the parents that would possibly interfere with the ability to comply to study procedures
  17. Major needle phobia that would complicate to wear pump catheter and sensor
  18. Congenital malformations that would interfere with diabetes treatment (e.g. congenital heart malformations, lung diseases, renal malformations)
  19. Growth hormone deficiency
  20. Combined Hypopituitarism
  21. Down Syndrome (high risk for comorbidity with coeliac disease, autoimmune thyroiditis)
  22. Cancer under treatment
  23. Current participation in other interventional clinical trials
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
81 participants (actual)

Study arms

  • Experimental
    Automated closed loop insulin delivery (intervention arm)

    Unsupervised home use of day and night automated hybrid closed loop insulin delivery system over 16 weeks. Intervention: Device: CamAPS FX

    Device: CamAPS FX

  • Active comparator
    Sensor augmented pump therapy (control arm)

    Sensor augmented pump therapy over 16 weeks.

    Other: Sensor augmented therapy

Interventions

  • DeviceCamAPS FX

    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

  • OtherSensor augmented therapy

    Study insulin pump and study CGM.

05

What researchers measure

Primary outcomes

  1. Time in Target (3.9 to 10.0 mmol/l) (70 to 180 mg/dl)

    Between group difference in time spent with sensor glucose levels between 3.9 to 10.0 mmol/l (70 to 180 mg/dl) during the 4 months intervention period.

    Time frame: 16-week home stay

Secondary outcomes

  1. Key Endpoint: 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)

    Time frame: 16-week home stay

  2. Key Endpoint: HbA1c

    HbA1c is measured in % as per NGSP

    Time frame: 16-week home stay

  3. Key Endpoint: HbA1c

    HbA1c, measured using standardized, validated assays, serves as an indicator of long-term glycemic control, reflecting the average blood glucose levels over approximately 3 months.

    Time frame: 16 weeks

  4. Key Endpoint: Mean Sensor Glucose

    Mean sensor glucose is calculated from CGM readings over the study period to reflect overall glycemic control.

    Time frame: 16-week home stay

  5. Key Endpoint: 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)

    Time frame: 16-week home stay

  6. Standard Deviation

    Standard deviation of sensor glucose levels

    Time frame: 16-week home stay

  7. Coefficient of Variation (Percentage) of Glucose Levels

    Coefficient of variation (percentage) of sensor glucose levels

    Time frame: 16-week home stay

  8. Time With Glucose Levels <3.0 mmol/l (54 mg/dl)

    Percentage of time spent with glucose levels \< 3.0mmol/l (54 mg/dl)

    Time frame: 16-week home stay

  9. 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)

    Time frame: 16-week home stay

  10. AUC of Glucose Below 3.5 mmol/l (63 mg/dl)

    Area under the curve of sensor glucose readings below 3.5mmol/l (63mg/dl). Glucose AUC was calculated by trapezoidal approximation of sensor glucose levels.

    Time frame: 16-week home stay

  11. BMI SDS

    BMI Standard Deviation Score

    Time frame: 16-week home stay

  12. Total, Basal, and Bolus Insulin Dose

    Median daily total, basal and bolus insulin use

    Time frame: 16-week home stay

  13. Number of Episodes of Severe Hypoglycaemia

    This outcome measure records the total number of severe hypoglycaemic episodes-defined as events requiring external assistance-experienced during the study period. Episodes are captured through patient records and clinical confirmation.

    Time frame: 16-week home stay

  14. Number of Subjects Experiencing Severe Hypoglycaemia

    Count of subjects with at least one severe hypoglycaemic event during the study. Severe events are defined as episodes requiring external assistance.

    Time frame: 16-week home stay

  15. Frequency of Diabetic Ketoacidosis

    The incidence of diabetic ketoacidosis (DKA) episodes will be recorded as the number of confirmed events during the study

    Time frame: 16-week home stay

  16. Frequency and Nature of Other Adverse Events

    The frequency and nature of other adverse events will be recorded throughout the study. All events not directly linked to the intervention will be documented, detailing their onset, duration, severity, and potential relation to the treatment.

    Time frame: 16-week home stay

  17. Percentage of Time of CGM Availability

    This outcome assesses the percentage of time the continuous glucose monitoring (CGM) system is active and delivering valid data.

    Time frame: 16-week home stay

  18. Percentage of Time of Closed-loop Operation

    This outcome measure determines the percentage of the total study period during which the closed-loop insulin delivery system operates as intended.

    Time frame: 16-week home stay

  19. Frequency and Nature of Other Serious Adverse Events

    Frequency and nature of other serious adverse events will be documented, including type, severity, and potential treatment association.

    Time frame: 16-week home stay

06

Results

Posted Mar 27, 2025

Participant flow

81 participants were enrolled between 17 May 201 9 and 16 June 2020 at 7 paediatric diabetes centres in the UK, Luxembourg, Austria and Germany.

Period 1
Participant flow — Period 1
MilestoneClosed-loop Insulin Delivery (Intervention), Then Sensor-augmented Pump Therapy (Control)Sensor Augmented Pump Therapy (Control), Then Closed-loop Insulin Delivery (Intervention)
Started3935
Completed3934
Not completed01
Withdrew: Withdrawal by subject01
Washout
Participant flow — Washout
MilestoneClosed-loop Insulin Delivery (Intervention), Then Sensor-augmented Pump Therapy (Control)Sensor Augmented Pump Therapy (Control), Then Closed-loop Insulin Delivery (Intervention)
Started3934
Completed3934
Not completed00
Period 2
Participant flow — Period 2
MilestoneClosed-loop Insulin Delivery (Intervention), Then Sensor-augmented Pump Therapy (Control)Sensor Augmented Pump Therapy (Control), Then Closed-loop Insulin Delivery (Intervention)
Started3934
Completed3934
Not completed00

Outcome measures

PrimaryTime in Target (3.9 to 10.0 mmol/l) (70 to 180 mg/dl)

Between group difference in time spent with sensor glucose levels between 3.9 to 10.0 mmol/l (70 to 180 mg/dl) during the 4 months intervention period.

Time frame:
16-week home stay
Reported as:
Mean · Percent of time spent in target range
Time in Target (3.9 to 10.0 mmol/l) (70 to 180 mg/dl)
Percent of time spent in target rangeClosed-loop PeriodSensor-augmented Pump Period
Time in Target (3.9 to 10.0 mmol/l) (70 to 180 mg/dl)71.6 ± 5.962.9 ± 9.0
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Regression, Linear · p = <0.001 · Mean difference (final values): 8.7 · 95% CI 7.4 to 9.9The mean adjusted differences are based on a linear mixed model with adjustment for repeated participant measures, with period as a fixed effect and trial site as a random effect; the model also accounted for the baseline values.
SecondaryKey Endpoint: 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)

Time frame:
16-week home stay
Reported as:
Median · Percent of time spent
Key Endpoint: Time Spent Above Target Glucose (10.0 mmol/l) (180 mg/dl)
Percent of time spentClosed-loop PeriodSensor-augmented Pump Period
Key Endpoint: Time Spent Above Target Glucose (10.0 mmol/l) (180 mg/dl)22.9 (19.3 to 27.3)31.7 (23.4 to 40.1)
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Regression, Linear · p = <0.001 (The primary and key secondary end points were tested in hierarchy (Time in range, time \>180mg/dL, HbA1c, mean glucose, time \<70mg/dL) to control the type 1 error with the use of the fixed-sequence method.) · Mean difference (final values): -8.5 · 95% CI -9.9 to -7.1The mean adjusted differences are based on a linear mixed model with adjustment for repeated participant measures, with period as a fixed effect and trial site as a random effect; the model also accounted for the baseline values.
SecondaryKey Endpoint: HbA1c

HbA1c is measured in % as per NGSP

Time frame:
16-week home stay
Reported as:
Mean · % of glucose linked to haemoglobin molec
Key Endpoint: HbA1c
% of glucose linked to haemoglobin molecClosed-loop PeriodSensor-augmented Pump Period
Key Endpoint: HbA1c6.6 ± 0.67.0 ± 0.7
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Regression, Linear · p = <0.001 (The primary and key secondary end points were tested in hierarchy (Time in range, time \>180mg/dL, HbA1c, mean glucose, time \<70mg/dL) to control the type 1 error with the use of the fixed-sequence method.) · Mean difference (final values): -0.4 · 95% CI -0.5 to -0.3The mean adjusted differences are based on a linear mixed model with adjustment for repeated participant measures, with period as a fixed effect and trial site as a random effect; the model also accounted for the baseline values.
SecondaryKey Endpoint: HbA1c

HbA1c, measured using standardized, validated assays, serves as an indicator of long-term glycemic control, reflecting the average blood glucose levels over approximately 3 months.

Time frame:
16 weeks
Reported as:
Mean · mmol/mol
Key Endpoint: HbA1c
mmol/molClosed-loop PeriodSensor-augmented Pump Period
Key Endpoint: HbA1c49.0 ± 5.952.8 ± 7.2
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Mixed Models Analysis · p = <0.001 · Mean difference (final values): -3.9 · 95% CI -4.9 to -2.9
SecondaryKey Endpoint: Mean Sensor Glucose

Mean sensor glucose is calculated from CGM readings over the study period to reflect overall glycemic control.

Time frame:
16-week home stay
Reported as:
Mean · mg/dL
Key Endpoint: Mean Sensor Glucose
mg/dLClosed-loop PeriodSensor-augmented Pump Period
Key Endpoint: Mean Sensor Glucose145.8 ± 11.8158.1 ± 18.5
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Regression, Linear · p = <0.001 (The primary and key secondary end points were tested in hierarchy (Time in range, time \>180mg/dL, HbA1c, mean glucose, time \<70mg/dL) to control the type 1 error with the use of the fixed-sequence method.) · Mean difference (final values): -12.3 · 95% CI -14.8 to -9.8The mean adjusted differences are based on a linear mixed model with adjustment for repeated participant measures, with period as a fixed effect and trial site as a random effect; the model also accounted for the baseline values.
SecondaryKey Endpoint: 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)

Time frame:
16-week home stay
Reported as:
Median · Percent of time spent
Key Endpoint: Time Spent Below Target Glucose (3.9 mmol/l) (70 mg/dl)
Percent of time spentClosed-loop PeriodSensor-augmented Pump Period
Key Endpoint: Time Spent Below Target Glucose (3.9 mmol/l) (70 mg/dl)4.9 (3.3 to 6.7)4.5 (2.9 to 7.3)
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Regression, Linear · p = 0.74 (The primary and key secondary end points were tested in hierarchy (Time in range, time \>180mg/dL, HbA1c, mean glucose, time \<70mg/dL) to control the type 1 error with the use of the fixed-sequence method.) · Mean difference (final values): 0.1 · 95% CI -0.4 to 0.5
SecondaryStandard Deviation

Standard deviation of sensor glucose levels

Time frame:
16-week home stay
Reported as:
Median · mg/dL
Standard Deviation
mg/dLClosed-loop PeriodSensor-augmented Pump Period
Standard Deviation58.6 (53.7 to 64.4)64.2 (58.1 to 71.9)
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Mean difference (final values): -6.2 · 95% CI -7.6 to -4.8Confidence intervals for the secondary end points were adjusted for multiple comparisons with the use of the Benjamini-Hochberg procedure to control the false discovery rate.
SecondaryCoefficient of Variation (Percentage) of Glucose Levels

Coefficient of variation (percentage) of sensor glucose levels

Time frame:
16-week home stay
Reported as:
Median · Percent
Coefficient of Variation (Percentage) of Glucose Levels
PercentClosed-loop PeriodSensor-augmented Pump Period
Coefficient of Variation (Percentage) of Glucose Levels41 (39 to 43)41 (38 to 44)
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Mean difference (final values): -0.7 · 95% CI -1.5 to 0.05Confidence intervals for the secondary end points were adjusted for multiple comparisons with the use of the Benjamini-Hochberg procedure to control the false discovery rate.
SecondaryTime With Glucose Levels <3.0 mmol/l (54 mg/dl)

Percentage of time spent with glucose levels \< 3.0mmol/l (54 mg/dl)

Time frame:
16-week home stay
Reported as:
Median · Percent of time spent
Time With Glucose Levels <3.0 mmol/l (54 mg/dl)
Percent of time spentClosed-loop PeriodSensor-augmented Pump Period
Time With Glucose Levels <3.0 mmol/l (54 mg/dl)1.0 (0.6 to 1.4)0.9 (0.4 to 1.6)
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Mean difference (final values): 0.02 · 95% CI -0.1 to 0.1Confidence intervals for the secondary end points were adjusted for multiple comparisons with the use of the Benjamini-Hochberg procedure to control the false discovery rate.
SecondaryTime 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)

Time frame:
16-week home stay
Reported as:
Median · Percent of time spent
Time With Glucose Levels in Significant Hyperglycaemia (Glucose Levels > 16.7 mmol/l) (300 mg/dl)
Percent of time spentClosed-loop PeriodSensor-augmented Pump Period
Time With Glucose Levels in Significant Hyperglycaemia (Glucose Levels > 16.7 mmol/l) (300 mg/dl)2.0 (1.2 to 3.1)3.1 (1.3 to 5.7)
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Mean difference (final values): -1.0 · 95% CI -1.6 to -0.6Confidence intervals for the secondary end points were adjusted for multiple comparisons with the use of the Benjamini-Hochberg procedure to control the false discovery rate.
SecondaryAUC of Glucose Below 3.5 mmol/l (63 mg/dl)

Area under the curve of sensor glucose readings below 3.5mmol/l (63mg/dl). Glucose AUC was calculated by trapezoidal approximation of sensor glucose levels.

Time frame:
16-week home stay
Reported as:
Median · mg*min/dL
AUC of Glucose Below 3.5 mmol/l (63 mg/dl)
mg*min/dLClosed-loop PeriodSensor-augmented Pump Period
AUC of Glucose Below 3.5 mmol/l (63 mg/dl)0.1 (0.0 to 0.1)0.1 (0.0 to 0.1)
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Mean difference (final values): 0.002 · 95% CI -0.006 to 0.009Confidence intervals for the secondary end points were adjusted for multiple comparisons with the use of the Benjamini-Hochberg procedure to control the false discovery rate.
SecondaryBMI SDS

BMI Standard Deviation Score

Time frame:
16-week home stay
Reported as:
Mean · Percentile
BMI SDS
PercentileClosed-loop PeriodSensor-augmented Pump Period
BMI SDS71 ± 2370 ± 26
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Regression, Linear · p = 0.75 · Mean difference (final values): 0.004 · 95% CI -0.02 to 0.03Based on a longitudinal model adjusting for baseline value and period as fixed effects. The model accounts for correlated data from the same subject.
SecondaryTotal, Basal, and Bolus Insulin Dose

Median daily total, basal and bolus insulin use

Time frame:
16-week home stay
Reported as:
Median · Units/day
Total, Basal, and Bolus Insulin Dose
Units/dayClosed-loop PeriodSensor-augmented Pump Period
Total daily insulin use16.9 (13.2 to 21.5)17.6 (13.6 to 20.3)
Total daily basal insulin use8.0 (5.8 to 10.9)5.7 (4.0 to 6.9)
Total daily bolus insulin use8.6 (6.9 to 10.6)11.0 (9.1 to 13.5)
Statistical analysis
  • Closed-loop Period vs Sensor-augmented Pump Period · Mean difference (final values): 0.3 · 95% CI -0.1 to 0.8(For total daily insulin use) Confidence intervals for the secondary end points were adjusted for multiple comparisons with the use of the Benjamini-Hochberg procedure to control the false discovery rate.
SecondaryNumber of Episodes of Severe Hypoglycaemia

This outcome measure records the total number of severe hypoglycaemic episodes-defined as events requiring external assistance-experienced during the study period. Episodes are captured through patient records and clinical confirmation.

Time frame:
16-week home stay
Reported as:
Number · number of events
Number of Episodes of Severe Hypoglycaemia
number of eventsClosed-loop PeriodSensor-augmented Pump Period
Number of Episodes of Severe Hypoglycaemia10
SecondaryNumber of Subjects Experiencing Severe Hypoglycaemia

Count of subjects with at least one severe hypoglycaemic event during the study. Severe events are defined as episodes requiring external assistance.

Time frame:
16-week home stay
Reported as:
Count of participants · Participants
Number of Subjects Experiencing Severe Hypoglycaemia
ParticipantsClosed-loop PeriodSensor-augmented Pump Period
Number of Subjects Experiencing Severe Hypoglycaemia10
SecondaryFrequency of Diabetic Ketoacidosis

The incidence of diabetic ketoacidosis (DKA) episodes will be recorded as the number of confirmed events during the study

Time frame:
16-week home stay
Reported as:
Count of participants · Participants
Frequency of Diabetic Ketoacidosis
ParticipantsClosed-loop PeriodSensor-augmented Pump Period
Frequency of Diabetic Ketoacidosis00
SecondaryFrequency and Nature of Other Adverse Events

The frequency and nature of other adverse events will be recorded throughout the study. All events not directly linked to the intervention will be documented, detailing their onset, duration, severity, and potential relation to the treatment.

Time frame:
16-week home stay
Reported as:
Count of participants · Participants
Frequency and Nature of Other Adverse Events
ParticipantsClosed-loop PeriodSensor-augmented Pump Period
Number of participants with no adverse events5356
Number of participants with one adverse event1512
Number of participants with two or more adverse events56
SecondaryPercentage of Time of CGM Availability

This outcome assesses the percentage of time the continuous glucose monitoring (CGM) system is active and delivering valid data.

Time frame:
16-week home stay
Reported as:
Median · Time using CGM (%)
Percentage of Time of CGM Availability
Time using CGM (%)Closed-loop PeriodSensor-augmented Pump Period
Percentage of Time of CGM Availability99 (99 to 100)99 (99 to 100)
SecondaryPercentage of Time of Closed-loop Operation

This outcome measure determines the percentage of the total study period during which the closed-loop insulin delivery system operates as intended.

Time frame:
16-week home stay
Reported as:
Median · Time using closed-loop (%)
Percentage of Time of Closed-loop Operation
Time using closed-loop (%)Closed-loop Period
Percentage of Time of Closed-loop Operation95 (92 to 97)
SecondaryFrequency and Nature of Other Serious Adverse Events

Frequency and nature of other serious adverse events will be documented, including type, severity, and potential treatment association.

Time frame:
16-week home stay
Reported as:
Count of participants · Participants
Frequency and Nature of Other Serious Adverse Events
ParticipantsClosed-loop PeriodSensor-augmented Pump Period
Frequency and Nature of Other Serious Adverse Events01

Adverse events

Collected over Over both 16-week study periods (total 32 weeks).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Closed-loop Period0/73 (0%)1/73 (1.4%)20/73 (27.4%)
Sensor-augmented Pump Period0/74 (0%)1/74 (1.4%)18/74 (24.3%)
Most frequent serious events
Most frequent serious events
EventClosed-loop PeriodSensor-augmented Pump Period
Severe hypoglycaemia eventEndocrine disorders1/730/74
Other serious adverse event.Gastrointestinal disorders0/731/74
Most frequent other events
Most frequent other events
EventClosed-loop PeriodSensor-augmented Pump Period
Infection (Cold, UTI, D&V, fever)Infections and infestations16/7311/74
HyperglycaemiaEndocrine disorders2/736/74
Diabetes relatedProduct Issues2/730/74
Head injuryNervous system disorders0/731/74

Baseline characteristics

Age, Continuous
Age, Continuous(years)Closed-loop Insulin Delivery First, Then Sensor-augmented Pump TherapySensor Augmented Pump Therapy First, Then Closed-loop Insulin DeliveryTotal
Mean5.6 ± 1.45.6 ± 1.75.6 ± 1.6
Sex: Female, Male
Sex: Female, Male(Participants)Closed-loop Insulin Delivery First, Then Sensor-augmented Pump TherapySensor Augmented Pump Therapy First, Then Closed-loop Insulin DeliveryTotal
Female211031
Male182543
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Closed-loop Insulin Delivery First, Then Sensor-augmented Pump TherapySensor Augmented Pump Therapy First, Then Closed-loop Insulin DeliveryTotal
White343266
Black202
Asian112
Multiple224
Duration of diabetes
Duration of diabetes(years)Closed-loop Insulin Delivery First, Then Sensor-augmented Pump TherapySensor Augmented Pump Therapy First, Then Closed-loop Insulin DeliveryTotal
Mean2.5 ± 1.72.7 ± 1.92.6 ± 1.8
Continuous Glucose Monitor Use
Continuous Glucose Monitor Use(Participants)Closed-loop Insulin Delivery First, Then Sensor-augmented Pump TherapySensor Augmented Pump Therapy First, Then Closed-loop Insulin DeliveryTotal
Current353267
In past but not current011
Never426
BMI percentile (age- and sex-adjusted)
BMI percentile (age- and sex-adjusted)(percentile)Closed-loop Insulin Delivery First, Then Sensor-augmented Pump TherapySensor Augmented Pump Therapy First, Then Closed-loop Insulin DeliveryTotal
Mean67.3 ± 23.271.1 ± 24.669.1 ± 23.8
HbA1c at screening
HbA1c at screening(% of glucose linked to haemoglobin)Closed-loop Insulin Delivery First, Then Sensor-augmented Pump TherapySensor Augmented Pump Therapy First, Then Closed-loop Insulin DeliveryTotal
Mean7.3 ± 0.77.4 ± 0.67.3 ± 0.7
HbA1c
HbA1c(mmol/mol)Closed-loop Insulin Delivery First, Then Sensor-augmented Pump TherapySensor Augmented Pump Therapy First, Then Closed-loop Insulin DeliveryTotal
Mean56.3 ± 7.457 ± 7.156.6 ± 7.2

6 further baseline measures are reported on the registry.

07

Study locations

8 sites
  • Medical University of Graz Department of Pediatrics and Adolescent Medicine
    Graz, A-8036, Austria
  • Medical University of Innsbruck Department of Pediatrics I
    Innsbruck, A-6020, Austria
  • Medical University of Vienna Department of Pediatrics
    Wien, A-1090, Austria
  • University of Leipzig Division for Paediatric Diabetology
    Leipzig, D-04103, Germany
  • Clinique Pédiatrique de Luxembourg Centre Hospitalier de Luxembourg
    Luxembourg, L-1210, Luxembourg
  • University Department of Paediatrics
    Cambridge, Cambridgeshire CB2 0QQ, United Kingdom
  • Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge
    Cambridge, Cambridgeshire CB2 0QQ, United Kingdom
  • St James's University Hospital
    Leeds, LS9 7TF, United Kingdom
08

References and documents

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 25512874 ↗
  • Thabit 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. 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 26379095 ↗
  • Tauschmann 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 26740634 ↗
  • Tauschmann 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 27612500 ↗
  • Ware J, Allen JM, Boughton CK, Wilinska ME, Hartnell S, Thankamony A, de Beaufort C, Schierloh U, Frohlich-Reiterer E, Mader JK, Kapellen TM, Rami-Merhar B, Tauschmann M, Nagl K, Hofer SE, Campbell FM, Yong J, Hood KK, Lawton J, Roze S, Sibayan J, Bocchino LE, Kollman C, Hovorka R; KidsAP Consortium. Randomized Trial of Closed-Loop Control in Very Young Children with Type 1 Diabetes. N Engl J Med. 2022 Jan 20;386(3):209-219. doi: 10.1056/NEJMoa2111673. PubMed 35045227 ↗
  • Fuchs J, Allen JM, Boughton CK, Wilinska ME, Thankamony A, de Beaufort C, Campbell F, Yong J, Froehlich-Reiterer E, Mader JK, Hofer SE, Kapellen TM, Rami-Merhar B, Tauschmann M, Hood K, Kimbell B, Lawton J, Roze S, Sibayan J, Cohen N, Hovorka R; KidsAP Consortium. Assessing the efficacy, safety and utility of closed-loop insulin delivery compared with sensor-augmented pump therapy in very young children with type 1 diabetes (KidsAP02 study): an open-label, multicentre, multinational, randomised cross-over study protocol. BMJ Open. 2021 Feb 12;11(2):e042790. doi: 10.1136/bmjopen-2020-042790. PubMed 33579766 ↗

Study documents

  • Protocol and statistical analysis plan · May 5, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: 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.

Supporting information: Study protocol, Sap

09

Registry details

Key details

Study ID
NCT03784027
Lead sponsor
University of Cambridge
Collaborators
European Commission, 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, University of Edinburgh, Stanford University, Glooko
Responsible party
Dr Roman Hovorka (Study Director, University of Cambridge) — Principal investigator
First posted
Dec 21, 2018
Start date
May 1, 2019
Primary completion
Feb 22, 2021
Completion
Oct 3, 2022
Results posted
Mar 27, 2025
Last update
Mar 27, 2025

Study contacts

Roman Hovorka
study director · Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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