Diabetes MellitusDAN05NCT02925299
Day and Night Closed-loop in Young People With Type 1 Diabetes
A study testing FlorenceM (US) and FlorenceX (UK) and Insulin pump therapy in people with Diabetes Mellitus and Diabetes Mellitus, Type 1, run by Jaeb Center for Health Research at 11 sites in 2 countries.
Trial summary
The main study objective is to determine whether 24/7 automated closed-loop glucose control combined with low glucose feature will improve glucose control as measured by HbA1c. This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a 6 month period of… Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders
- What is being tested?
- FlorenceM (US) and FlorenceX (UK) and Insulin pump therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 133 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 12 May 2017to 27 Aug 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≥6 and <19 years
- Type 1 diabetes as defined by WHO (51) for at least 1 year [WHO definition: 'The aetiological type named type 1 encompasses the majority of cases with 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.).']
- Use of an insulin pump for at least 3 months, with good knowledge of insulin self-adjustment by subject or caregiver as judged by the investigator
- Using U-100 rapid acting insulin analogues insulin Aspart or Lispro only
- Willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements per day day
- Screening HbA1c ≥ 7.0% (53 mmol/mol) and ≤10 % (86mmol/mol) based on analysis from local laboratory
Show all 13Show fewer
- Literate in English
- Willing to wear glucose sensor
- Willing to wear closed-loop system at home
- Willing to follow study specific instructions
- Willing to upload pump and CGM data at regular intervals
- Access to WiFi.
- Lives with someone who is trained to administer intramuscular glucagon and is able to seek emergency assistance
Who cannot join
- Living alone
- Current use of any closed-loop system
- Any other 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, adrenal insufficiency, or untreated thyroid disease
- Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc.
- Known or suspected allergy to insulin
Show all 27Show fewer
- Clinically significant nephropathy (eGFR < 45ml/min) or on dialysis, neuropathy or active retinopathy (defined as presence of maculopathy or proliferative changes) as judged by the investigator
- Recurrent incidents of severe hypoglycaemia (>1 episode) during the previous 6 months (adolescents: severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions including episodes of hypoglycaemia severe enough to cause unconsciousness, seizures or attendance at hospital; children: severe hypoglycaemia is defined as an event associated with a seizure or loss of consciousness)
- Recurrent incidents of diabetic ketoacidosis (>1 episode) during previous 6 months
- Unwilling to avoid regular use of acetaminophen
- Lack of reliable telephone facility for contact
- Total daily insulin dose ≥ 2 IU/kg/day
- Total daily insulin dose < 15 IU/day
- Pregnancy, planned pregnancy, or breast feeding
- Severe visual impairment
- Severe hearing impairment
- Seizure disorder
- Medically documented allergy towards the adhesive (glue) of plasters or unable to tolerate tape adhesive in the area of sensor placement
- Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located at places of the body, which potentially are possible to be used for localisation of the glucose sensor)
- Illicit drugs abuse
- Subject is currently abusing prescription drugs
- Alcohol abuse
- Use of pramlintide (Symlin), or other non-insulin glucose lowering agents including sulphonylureas, biguanides, DPP4-Inhibitors, , GLP-1 analogues, SGLT-1/ 2 inhibitors at time of screening
- Shift work with working hours between 10pm and 8am
- Sickle cell disease, haemoglobinopathy, or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
- Eating disorder such as anorexia or bulimia
- Employed by Medtronic Diabetes or with immediate family members employed by Medtronic Diabetes
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United Kingdom6 sites
University of Cambridge
Cambridge, Cambridgeshire County, CB2 0QQ
The Leeds Teaching Hospitals NHS Trust
Leeds, West Yorkshire, LS9 7TF
Alder Hey Children's NHS Foundation Trust
Liverpool
Nottingham Children's Hospital
Nottingham, England, NG5 1PB
Oxford Children's Hospital
Oxford
Southampton Children's Hospital
Southampton, England, SO16 6YD
United States5 sites
University of Colorado Denver School of Medicine Barbara Davis Center
Aurora, Colorado, 80045
Yale University
Hartford, Connecticut, 06520
Indiana University
Indianapolis, Indiana, 43202
Nemours Children's Health System
Jacksonville, Florida, 32207
Stanford University
Palo Alto, California, 95032
About this study
Official title: An Open-label, Multi-centre, Randomized, Single-period, Parallel Study to Assess the Efficacy, Safety and Utility of 6 Month Day-and-night Automated Closed-loop Insulin Delivery Under Free Living Conditions Compared to Insulin Pump Therapy in Children and Adolescents With Type 1 Diabetes
The main study objective is to determine whether 24/7 automated closed-loop glucose control combined with low glucose feature will improve glucose control as measured by HbA1c.
This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a 6 month period of home study during which day and night glucose levels will be controlled either by a closed-loop system combined with low glucose feature (intervention group) or by insulin pump therapy alone (control group).
Read more
It is expected that a total of up to 150 subjects (aiming for 130 randomised subjects) with type 1 diabetes will be recruited through paediatric outpatient diabetes clinics of the investigation centres. Participants will all be on subcutaneous insulin pump therapy.
Subjects in the intervention group will have proven competencies both in the use of the study insulin pump and the study continuous glucose monitoring (CGM) device, and will receive appropriate training in the safe use of closed-loop insulin delivery system and low glucose feature. All subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is between group differences in HbA1c levels at 6 months post study arm initiation. Secondary outcomes are the time spent in the glucose target (3.9 to 10.0mmol/l; 70 to 180mg/dl), 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 of severe hypoglycaemic episodes and diabetic ketoacidosis (DKA).
Read the detailed description
- Purpose of the study: To determine whether 24/7 automated closed-loop glucose control will improve glucose control as measured by glycated haemoglobin and reduce the burden of hypoglycaemia compared to insulin pump therapy alone.
- Study Objectives:
- EFFICACY: The objective is to assess efficacy of day and night automated closed-loop glucose control in improving glucose control as measured by glycated haemoglobin, as compared to insulin pump therapy alone.
- SAFETY: The objective is to evaluate the safety of day and night automated closed-loop glucose control, in terms of episodes of severe hypoglycaemia and other adverse events.
- UTILITY: The objective is to determine the frequency and duration of the use of the automated closed-loop system.
- HUMAN FACTORS: The objective is to assess cognitive, emotional, and behavioural characteristics of participating subjects and family members and their response to the closed-loop system and clinical trial using validated surveys and focus groups.
- HEALTH ECONOMICS: The objective is to perform a cost utility analysis to inform reimbursement decision-making.
- Study Design: An open-label, multi-centre, randomised, single-period parallel study, contrasting day-and-night automated closed-loop glucose control with insulin pump therapy alone.
- Population: 130 participants randomised (equal proportion of those aged 6 to 12 years and 13 to 18 years, a minimum quota of 25% participants with baseline HbA1c >8.5%)
- Maximum duration of study for a subject: 8 months
- Recruitment: The subjects will be recruited through the pediatric outpatient clinics at each center.
- Consent: Written consent / assent will be obtained from participants and/or guardians according to REC / IRB requirements
- Screening Assessments: Eligible participants will undergo a screening evaluation where blood samples for full blood count, liver, thyroid function and anti-transglutaminase antibodies (with IgA levels if not done within previous 12 months) will be taken. Non-hypoglycaemia C-peptide, glucose and HbA1c will also be measured, and a urine pregnancy test in females of child-bearing potential will be performed.
Surveys investigating participants' quality of life, psychosocial and cognitive functioning, and response to their current treatment will be distributed.
Participants will be fitted with a blinded continuous glucose monitoring (CGM) device to assess baseline glycaemic control. Instructions on how to safely use, remove and send back the device will be provided.
- Study Training: Training sessions on the use of study CGM, insulin pump (and closed loop system for those randomized to be intervention group) will be provided by the research team. Training session on the use of real-time CGM and on how to interpret real-time and retrospective stored data will be provided to all subjects / carers using written material.
- Run-In Period: During a 1-2 week run-in period, subjects will continue using their own insulin pump. Data obtained from blinded CGM and pump downloads may be utilised for therapy adjustment.
- 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. Further training may be delivered as required.
- Randomization: Eligible subjects will be randomised using randomisation software to the use of real-time CGM and low glucose feature combined with day and night closed-loop or to conventional insulin pump therapy alone.
A blood sample will be taken for the measurement of HbA1c and a urine pregnancy test in females of child-bearing potential. A blood sample for centralised analysis of HbA1c will be taken if screening and randomisation are >28 days apart.
- Automated day and night closed-loop insulin delivery (intervention arm) combined with low glucose feature (interventional arm) - Participants in the closed-loop group will receive additional training sessions following randomisation covering the use of the study insulin pump and real-time CGM, prior to starting closed-loop insulin delivery. Once confident with the use of the study pump and CGM system, participants will receive training required for safe and effective use of the closed-loop system approximately 2-4 weeks after randomisation. During this 2-4 hour session participants will operate the system under the supervision of the clinical team. Competency on the use of closed-loop system will be evaluated. Thereafter, participants are expected to use closed-loop for 6 months without direct real-time remote monitoring.
- Insulin pump therapy (control arm) - Refresher training on key aspects of insulin pump therapy will be provided.
Subjects will continue using their own insulin pump for 6 months.
- 3-month and 6 month assessments:
- A blood sample will be taken for measurement of HbA1c and a urine pregnancy test in females of child-bearing potential.
- Validated surveys evaluating the impact of the devices employed on quality of life, psychosocial and cognitive functioning, diabetes management and treatment satisfaction will be completed.
- Participants of both study arms will be fitted with blinded CGM systems at the end of each follow up visit. The sensors will be worn at home for up to 14 days and will be sent back to the research team. 6 months only: Subjects/guardians will be invited to join follow-up focus groups to gather feedback and reactions to their current treatment (closed-loop or insulin pump), the clinical trial, and quality of life changes.
- Study Contacts: In between study visits, participants will be contacted by the study team (email or phone) once monthly in order to record any adverse events, device deficiencies, and changes in insulin settings, other medical conditions and/or medication.
In case of any technical device or problems related to 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.
--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.
Subjects will be asked to test and record blood ketones if their finger prick glucose is > 16.7mmol/l (300mg/dl) upon awakening, >300 for more than 1 hour, or >22.2mmo/l (400mg/dL) at any time as part of the safety assessment for DKA.
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 patients on safety grounds: A subject, parent, or 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 closed-loop intervention after consideration of the benefit/risk ratio. Possible reasons are:
- Serious adverse events
- Significant protocol violation or non-compliance
- Failure to satisfy competency assessment
- Decision by the investigator, or the sponsor, that termination is in the subject's best medical interest
- Pregnancy, planned pregnancy, or breast feeding
- Allergic reaction to insulin
Efforts will be made to retain subjects in follow up for the final primary outcome assessment even if the intervention is discontinued, unless the investigator believes that it will be harmful for the subject to continue in the trial.
- Conditions
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Endocrine System Diseases, Autoimmune Diseases
- Being tested
- FlorenceM (US) and FlorenceX (UK), Insulin pump therapy
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Endocrine System Diseases, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlorenceM (US) and FlorenceX (UK)Device
The automated closed loop system (FlorenceM in US) will consist of:
Next generation sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Guardian3 CGM and glucose suspend feature.
The automated closed loop system (FlorenceX in UK) will consist of:
The DANA Diabecare R insulin pump (Sooil Development, Korea) incorporating the Dexcom G6 CGM.
An Android smartphone containing the Cambridge model predictive algorithm and communicating wirelessly with the insulin pump using a proprietary translator device.
Insulin pump therapyDevice
Subjects will continue using their own insulin pump for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| 24/7 closed loop insulin delivery | Experimental | The study system includes (1) a CGM that measures glucose levels, (2) a computer program on a smartphone that determines how much insulin is needed, and (3) an insulin pump that delivers the insulin. The name of this closed-loop system used in the US is FlorenceM (Medtronic 640G pump and Guardian3 sensor). The name of this closed-loop system in the UK is FlorenceX (DANA pump and Dexcom sensor). Half of the individuals taking part in the study will use the closed-loop study system for 6 months. Receives: Device: FlorenceM (US) and FlorenceX (UK) |
| Insulin pump therapy | Active comparator | Half of the Subjects will continue using their own insulin pump for 6 months. Receives: Device: Insulin pump therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glycated Hemoglobin (HbA1c) at 6 Months.
The objective is to assess efficacy of day and night automated closed-loop glucose control combined with low glucose feature in improving HbA1c, as compared with insulin pump therapy alone.
Measured: HbA1c at 6 months
Secondary outcomes (14)
Time Spent in the Target Glucose Range (3.9 to 10mmol/l) (70 to 180mg/dl)
Secondary endpoints regarding glucose levels will be based on sensor glucose data.
Measured: 6 months
Time Spent Below Target Glucose (3.9mmol/l)(70mg/dl)
Secondary endpoints regarding glucose levels will be based on sensor glucose data.
Measured: 6 months
Time Spent Above Target Glucose (10.0 mmol/l) (180 mg/dl)
Secondary endpoints regarding glucose levels will be based on sensor glucose data.
Measured: 6 months
Mean and Standard Deviation Sensor Glucose
Secondary endpoints regarding glucose levels will be based on sensor glucose data.
Measured: 6 months
Time With Glucose Levels < 3.5 mmol/l (63 mg/dl)
Secondary endpoints regarding glucose levels will be based on sensor glucose data.
Measured: 6 months
Time With Glucose Levels <3.0 mmol/l (54 mg/dl)
Secondary endpoints regarding glucose levels will be based on sensor glucose data.
Measured: 6 months
Time With Glucose Levels in Significant Hyperglycaemia (Glucose Levels > 16.7 mmol/l) (300mg/dl)
Secondary endpoints regarding glucose levels will be based on sensor glucose data.
Measured: 6 months
Total Daily Insulin
Units/kg per day
Measured: 6 months
HbA1c <53 mmol/Mol (<7.0%)
Participants with HbA1c <53 mmol/mol (<7.5%) at 6 months
Measured: 6 months
HbA1c <58 mmol/Mol (<7.5%)
Participants with HbA1c <58 mmol/mol (<7.5%) at 6 months
Measured: 6 months
Relative Reduction ≥10%
Relative reduction in HbA1c ≥10% at 6 months
Measured: 6 months
HbA1c Absolute Reduction ≥0.5%
HbA1c absolute reduction ≥0.5% from baseline to 6 months
Measured: 6 months
HbA1c Absolute Reduction ≥1%
HbA1c absolute reduction ≥1% from baseline to 6 months
Measured: 6 months
HbA1c Absolute Reduction ≥1% or HbA1c <53 mmol/Mol (<7.0%)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2016 (estimated)
- Study start12 May 2017
- Primary completion27 Aug 2020
- Study completion27 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 133 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jaeb Center for Health Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Cambridge University Hospitals NHS Foundation Trust, University of Colorado, Denver, Indiana University, The Leeds Teaching Hospitals NHS Trust, Stanford University, Yale University, Nemours Children's Health System
- Responsible party
- Sponsor
- Investigators
- Roman Hovorka, PhD, Study chair, University of CambridgeAjay Thankamony, MD, Principal investigator, University of CambridgeFiona Campbell, MD, Principal investigator, The Leeds Teaching Hospitals NHS TrustBruce Buckingham, MD, Principal investigator, Stanford UniversityStuart Weinzimer, MD, Principal investigator, Yale UniversityLinda DiMeglio, MD, Principal investigator, Indiana UniversityPaul Wadwa, MD, Principal investigator, University of Colorado, DenverKorey Hood, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02925299
- Sponsor's protocol ID
- DAN05
- Other IDs
- 1UC4DK108520-01
- Acronym
- DAN05
- Status last verified
- Sep 2026
- First submitted
- 4 Oct 2016
- Last updated
- 15 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Ware J, Boughton CK, Allen JM, Wilinska ME, Tauschmann M, Denvir L, Thankamony A, Campbell FM, Wadwa RP, Buckingham BA, Davis N, DiMeglio LA, Mauras N, Besser REJ, Ghatak A, Weinzimer SA, Hood KK, Fox DS, Kanapka L, Kollman C, Sibayan J, Beck RW, Hovorka R; DAN05 Consortium. Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial. Lancet Digit Health. 2022 Apr;4(4):e245-e255. doi: 10.1016/S2589-7500(22)00020-6. Epub 2022 Mar 7.
PubMed 35272971Musolino G, Allen JM, Hartnell S, Wilinska ME, Tauschmann M, Boughton C, Campbell F, Denvir L, Trevelyan N, Wadwa P, DiMeglio L, Buckingham BA, Weinzimer S, Acerini CL, Hood K, Fox S, Kollman C, Sibayan J, Borgman S, Cheng P, Hovorka R. Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, multicentre, multinational, single-period, randomised, parallel group study protocol. BMJ Open. 2019 Jun 3;9(6):e027856. doi: 10.1136/bmjopen-2018-027856.
PubMed 31164368
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-centre, Randomized, Single-period, Parallel Study to Assess the Efficacy, Safety and Utility of 6 Month Day-and-night Automated Closed-loop Insulin Delivery Under Free Living Conditions Compared to Insulin Pump Therapy in Children and Adolescents With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT02925299
- Acronym / sponsor ID
- DAN05 / DAN05
- Conditions
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Endocrine System Diseases, Autoimmune Diseases
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 133 participants (actual)
- Lead sponsor
- Jaeb Center for Health ResearchUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Cambridge University Hospitals NHS Foundation Trust, University of Colorado, Denver, Indiana University, The Leeds Teaching Hospitals NHS Trust, Stanford University, Yale University, Nemours Children's Health System
- Study start
- 12 May 2017 (actual)
- Primary completion
- 27 Aug 2020 (actual)
- Study completion
- 27 Aug 2020 (actual)
- First posted
- 5 Oct 2016 (estimated)
- Results
- Posted 15 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main study objective is to determine whether 24/7 automated closed-loop glucose control combined with low glucose feature will improve glucose control as measured by HbA1c.
This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a 6 month period of home study during which day and night glucose levels will be controlled either by a closed-loop system combined with low glucose feature (intervention group) or by insulin pump therapy alone (control group).
It is expected that a total of up to 150 subjects (aiming for 130 randomised subjects) with type 1 diabetes will be recruited through paediatric outpatient diabetes clinics of the investigation centres. Participants will all be on subcutaneous insulin pump therapy.
Subjects in the intervention group will have proven competencies both in the use of the study insulin pump and the study continuous glucose monitoring (CGM) device, and will receive appropriate training in the safe use of closed-loop insulin delivery system and low glucose feature. All subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is between group differences in HbA1c levels at 6 months post study arm initiation. Secondary outcomes are the time spent in the glucose target (3.9 to 10.0mmol/l; 70 to 180mg/dl), 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 of severe hypoglycaemic episodes and diabetic ketoacidosis (DKA).
Detailed description
- Purpose of the study: To determine whether 24/7 automated closed-loop glucose control will improve glucose control as measured by glycated haemoglobin and reduce the burden of hypoglycaemia compared to insulin pump therapy alone.
- Study Objectives:
- EFFICACY: The objective is to assess efficacy of day and night automated closed-loop glucose control in improving glucose control as measured by glycated haemoglobin, as compared to insulin pump therapy alone.
- SAFETY: The objective is to evaluate the safety of day and night automated closed-loop glucose control, in terms of episodes of severe hypoglycaemia and other adverse events.
- UTILITY: The objective is to determine the frequency and duration of the use of the automated closed-loop system.
- HUMAN FACTORS: The objective is to assess cognitive, emotional, and behavioural characteristics of participating subjects and family members and their response to the closed-loop system and clinical trial using validated surveys and focus groups.
- HEALTH ECONOMICS: The objective is to perform a cost utility analysis to inform reimbursement decision-making.
- Study Design: An open-label, multi-centre, randomised, single-period parallel study, contrasting day-and-night automated closed-loop glucose control with insulin pump therapy alone.
- Population: 130 participants randomised (equal proportion of those aged 6 to 12 years and 13 to 18 years, a minimum quota of 25% participants with baseline HbA1c >8.5%)
- Maximum duration of study for a subject: 8 months
- Recruitment: The subjects will be recruited through the pediatric outpatient clinics at each center.
- Consent: Written consent / assent will be obtained from participants and/or guardians according to REC / IRB requirements
- Screening Assessments: Eligible participants will undergo a screening evaluation where blood samples for full blood count, liver, thyroid function and anti-transglutaminase antibodies (with IgA levels if not done within previous 12 months) will be taken. Non-hypoglycaemia C-peptide, glucose and HbA1c will also be measured, and a urine pregnancy test in females of child-bearing potential will be performed.
Surveys investigating participants' quality of life, psychosocial and cognitive functioning, and response to their current treatment will be distributed.
Participants will be fitted with a blinded continuous glucose monitoring (CGM) device to assess baseline glycaemic control. Instructions on how to safely use, remove and send back the device will be provided.
- Study Training: Training sessions on the use of study CGM, insulin pump (and closed loop system for those randomized to be intervention group) will be provided by the research team. Training session on the use of real-time CGM and on how to interpret real-time and retrospective stored data will be provided to all subjects / carers using written material.
- Run-In Period: During a 1-2 week run-in period, subjects will continue using their own insulin pump. Data obtained from blinded CGM and pump downloads may be utilised for therapy adjustment.
- 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. Further training may be delivered as required.
- Randomization: Eligible subjects will be randomised using randomisation software to the use of real-time CGM and low glucose feature combined with day and night closed-loop or to conventional insulin pump therapy alone.
A blood sample will be taken for the measurement of HbA1c and a urine pregnancy test in females of child-bearing potential. A blood sample for centralised analysis of HbA1c will be taken if screening and randomisation are >28 days apart.
- Automated day and night closed-loop insulin delivery (intervention arm) combined with low glucose feature (interventional arm) - Participants in the closed-loop group will receive additional training sessions following randomisation covering the use of the study insulin pump and real-time CGM, prior to starting closed-loop insulin delivery. Once confident with the use of the study pump and CGM system, participants will receive training required for safe and effective use of the closed-loop system approximately 2-4 weeks after randomisation. During this 2-4 hour session participants will operate the system under the supervision of the clinical team. Competency on the use of closed-loop system will be evaluated. Thereafter, participants are expected to use closed-loop for 6 months without direct real-time remote monitoring.
- Insulin pump therapy (control arm) - Refresher training on key aspects of insulin pump therapy will be provided.
Subjects will continue using their own insulin pump for 6 months.
- 3-month and 6 month assessments:
- A blood sample will be taken for measurement of HbA1c and a urine pregnancy test in females of child-bearing potential.
- Validated surveys evaluating the impact of the devices employed on quality of life, psychosocial and cognitive functioning, diabetes management and treatment satisfaction will be completed.
- Participants of both study arms will be fitted with blinded CGM systems at the end of each follow up visit. The sensors will be worn at home for up to 14 days and will be sent back to the research team. 6 months only: Subjects/guardians will be invited to join follow-up focus groups to gather feedback and reactions to their current treatment (closed-loop or insulin pump), the clinical trial, and quality of life changes.
- Study Contacts: In between study visits, participants will be contacted by the study team (email or phone) once monthly in order to record any adverse events, device deficiencies, and changes in insulin settings, other medical conditions and/or medication.
In case of any technical device or problems related to 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.
--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.
Subjects will be asked to test and record blood ketones if their finger prick glucose is > 16.7mmol/l (300mg/dl) upon awakening, >300 for more than 1 hour, or >22.2mmo/l (400mg/dL) at any time as part of the safety assessment for DKA.
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 patients on safety grounds: A subject, parent, or 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 closed-loop intervention after consideration of the benefit/risk ratio. Possible reasons are:
- Serious adverse events
- Significant protocol violation or non-compliance
- Failure to satisfy competency assessment
- Decision by the investigator, or the sponsor, that termination is in the subject's best medical interest
- Pregnancy, planned pregnancy, or breast feeding
- Allergic reaction to insulin
Efforts will be made to retain subjects in follow up for the final primary outcome assessment even if the intervention is discontinued, unless the investigator believes that it will be harmful for the subject to continue in the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 24/7 closed loop insulin delivery | Experimental | Device: FlorenceM (US) and FlorenceX (UK)The study system includes (1) a CGM that measures glucose levels, (2) a computer program on a smartphone that determines how much insulin is needed, and (3) an insulin pump that delivers the insulin. The name of this closed-loop system used in the US is FlorenceM (Medtronic 640G pump and Guardian3 sensor). The name of this closed-loop system in the UK is FlorenceX (DANA pump and Dexcom sensor). Half of the individuals taking part in the study will use the closed-loop study system for 6 months. |
| Insulin pump therapy | Active comparator | Device: Insulin pump therapyHalf of the Subjects will continue using their own insulin pump for 6 months. |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Age ≥6 and <19 years
- Type 1 diabetes as defined by WHO (51) for at least 1 year [WHO definition: 'The aetiological type named type 1 encompasses the majority of cases with 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.).']
- Use of an insulin pump for at least 3 months, with good knowledge of insulin self-adjustment by subject or caregiver as judged by the investigator
- Using U-100 rapid acting insulin analogues insulin Aspart or Lispro only
- Willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements per day day
Key exclusion criteria (27 listed)
- Living alone
- Current use of any closed-loop system
- Any other 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, adrenal insufficiency, or untreated thyroid disease
- Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc.
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 |
|---|---|---|
| FlorenceM (US) and FlorenceX (UK)The automated closed loop system (FlorenceM in US) will consist of: Next generation sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Guardian3 CGM and glucose suspend feature. The automated closed loop system (FlorenceX in UK) will consist of: The DANA Diabecare R insulin pump (Sooil Development, Korea) incorporating the Dexcom G6 CGM. An Android smartphone containing the Cambridge model predictive algorithm and communicating wirelessly with the insulin pump using a proprietary translator device. | Device | 24/7 closed loop insulin delivery |
| Insulin pump therapySubjects will continue using their own insulin pump for 6 months. | Device | Insulin pump therapy |
Primary outcome
Glycated Hemoglobin (HbA1c) at 6 Months.
Time frame: HbA1c at 6 months
The objective is to assess efficacy of day and night automated closed-loop glucose control combined with low glucose feature in improving HbA1c, as compared with insulin pump therapy alone.
14 secondary outcomes
Time Spent in the Target Glucose Range (3.9 to 10mmol/l) (70 to 180mg/dl)
Time frame: 6 months
Time Spent Below Target Glucose (3.9mmol/l)(70mg/dl)
Time frame: 6 months
Time Spent Above Target Glucose (10.0 mmol/l) (180 mg/dl)
Time frame: 6 months
Mean and Standard Deviation Sensor Glucose
Time frame: 6 months
Time With Glucose Levels < 3.5 mmol/l (63 mg/dl)
Time frame: 6 months
Time With Glucose Levels <3.0 mmol/l (54 mg/dl)
Time frame: 6 months
Time With Glucose Levels in Significant Hyperglycaemia (Glucose Levels > 16.7 mmol/l) (300mg/dl)
Time frame: 6 months
Total Daily Insulin
Time frame: 6 months
HbA1c <53 mmol/Mol (<7.0%)
Time frame: 6 months
HbA1c <58 mmol/Mol (<7.5%)
Time frame: 6 months
Relative Reduction ≥10%
Time frame: 6 months
HbA1c Absolute Reduction ≥0.5%
Time frame: 6 months
HbA1c Absolute Reduction ≥1%
Time frame: 6 months
HbA1c Absolute Reduction ≥1% or HbA1c <53 mmol/Mol (<7.0%)
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35272971Ware J, Boughton CK, Allen JM, Wilinska ME, Tauschmann M, Denvir L, Thankamony A, Campbell FM, Wadwa RP, Buckingham BA, Davis N, DiMeglio LA, Mauras N, Besser REJ, Ghatak A, Weinzimer SA, Hood KK, Fox DS, Kanapka L, Kollman C, Sibayan J, Beck RW, Hovorka R; DAN05 Consortium. Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial. Lancet Digit Health. 2022 Apr;4(4):e245-e255. doi: 10.1016/S2589-7500(22)00020-6. Epub 2022 Mar 7.
- Derived from this study: PubMed 31164368Musolino G, Allen JM, Hartnell S, Wilinska ME, Tauschmann M, Boughton C, Campbell F, Denvir L, Trevelyan N, Wadwa P, DiMeglio L, Buckingham BA, Weinzimer S, Acerini CL, Hood K, Fox S, Kollman C, Sibayan J, Borgman S, Cheng P, Hovorka R. Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, multicentre, multinational, single-period, randomised, parallel group study protocol. BMJ Open. 2019 Jun 3;9(6):e027856. doi: 10.1136/bmjopen-2018-027856.
- Individual participant dataSharing planned: No
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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 chair
University of Cambridge
Ajay Thankamony, MD principal investigator
University of Cambridge
Fiona Campbell, MD principal investigator
The Leeds Teaching Hospitals NHS Trust
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing FlorenceM (US) and FlorenceX (UK) and Insulin pump therapy in people with Diabetes Mellitus and Diabetes Mellitus, Type 1, run by Jaeb Center for Health Research at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 27 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 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United Kingdom, United States. 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?
Yes. Results are posted in the registry (first posted 15 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Glycated Hemoglobin (HbA1c) at 6 Months. (time frame: HbA1c at 6 months). 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 NCT02925299, which also lists 2 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 15 Oct 2026.