Day and Night Closed-loop in Young People With Type 1 Diabetes (DAN05)
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|ClinicalTrials.gov Identifier: NCT02925299|
Recruitment Status : Recruiting
First Posted : October 5, 2016
Last Update Posted : October 3, 2019
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).
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus Diabetes Mellitus, Type 1 Glucose Metabolism Disorders Endocrine System Diseases Autoimmune Diseases||Device: FlorenceM (US) and FlorenceX (UK) Device: Insulin pump therapy||Not Applicable|
Hide 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.
- 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||130 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||May 12, 2017|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||June 2020|
Experimental: 24/7 closed loop insulin delivery
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.
Device: 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.
Active Comparator: Insulin pump therapy
Half of the Subjects will continue using their own insulin pump for 6 months.
Device: Insulin pump therapy
Subjects will continue using their own insulin pump for 6 months.
- The primary outcome is the centralised measurement of glycated haemoglobin (HbA1c) at 6 months. [ Time Frame: HbA1c will be taken at baseline, 3 and 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.
- Time spent in the target glucose range (3.9 to 10mmol/l) (70 to 180mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Time spent below target glucose (3.9mmol/l)(70mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Time spent above target glucose (10.0 mmol/l) (180 mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Mean and standard deviation or percentiles sensor glucose [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Coefficient of variation of glucose levels [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Time with glucose levels < 3.5 mmol/l (63 mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Time with glucose levels <3.0 mmol/l (54 mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Time with glucose levels in significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Changes in total basal and bolus insulin dose [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on CRF and insulin pump data.
- AUC of glucose below 3.5mmol/l (63mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- AUC glucose above 10.0mmol/L (180mg/dL) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- HbA1c <7.0%, HbA1c <7.5%, Relative reduction ≥10% from baseline. o Absolute reduction ≥0.5% from baseline o Absolute reduction ≥1% from baseline o Absolute reduction ≥1% from baseline or HbA1c <7.0% [ Time Frame: 6 months ]Binary metrics for HbA1c
- Safety Evaluation [ Time Frame: 6 months ]Frequency of severe hypoglycaemic episodes as defined by American Diabetes Association (adolescents), and International Society for Pediatric and Adolescent Diabetes (children), frequency of diabetic ketoacidosis (DKA), frequency of severe hyperglycaemia (>16.7 mmol/l)(>300mg/dl) with significant ketosis (plasma ketones >0.6mmol/l) and nature and severity of other adverse events
- Utility evaluation [ Time Frame: 6 months ]Assessment of the frequency and duration of use of the closed-loop system
- Human Factors Assessment [ Time Frame: 6 months ]Cognitive, emotional, and behavioural characteristics of participating subjects and family members and their response to the closed-loop system and clinical trial will be assessed gathering both quantitative (validated surveys) and qualitative data (focus groups)
- Health Economic Evaluation [ Time Frame: 6 months ]Cost utility analysis on the benefits of closed loop insulin delivery to inform reimbursement decision-making
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02925299
|Contact: Roman Hovorka, PhD||+44 1223 762 firstname.lastname@example.org|
|Contact: Judy Sibayan, MPH, CCRPemail@example.com|
|United States, California|
|Stanford University||Active, not recruiting|
|Palo Alto, California, United States, 95032|
|United States, Colorado|
|University of Colorado Denver School of Medicine Barbara Davis Center||Active, not recruiting|
|Aurora, Colorado, United States, 80045|
|United States, Connecticut|
|Yale University||Active, not recruiting|
|Hartford, Connecticut, United States, 06520|
|United States, Florida|
|Nemours Children's Health System||Active, not recruiting|
|Jacksonville, Florida, United States, 32207|
|United States, Indiana|
|Indiana University||Active, not recruiting|
|Indianapolis, Indiana, United States, 43202|
|University of Cambridge||Recruiting|
|Cambridge, Cambridgeshire County, United Kingdom, CB2 0QQ|
|Contact: Charlotte Boughton, MD +44 1229 769066 firstname.lastname@example.org|
|Contact: Janet Allen, RN 44 1223 769064 email@example.com|
|Principal Investigator: Carlo Acerini, MD|
|Nottingham Children's Hospital||Recruiting|
|Nottingham, England, United Kingdom, NG5 1PB|
|Contact: Louise Denvir, MD 44 115 924 9924 ext 62336 Louise.firstname.lastname@example.org|
|Contact: Maria Saxton 0115 924 9924 ext 70680 Maria.Saxton@nuh.nhs.uk|
|Southampton Children's Hospital||Recruiting|
|Southampton, England, United Kingdom, SO16 6YD|
|Contact: Nikki Davis, MD email@example.com|
|Contact: Helen Dewar 023 8120 4989 Helen.Dewar@uhs.nhs.net|
|The Leeds Teaching Hospitals NHS Trust||Recruiting|
|Leeds, West Yorkshire, United Kingdom, LS9 7TF|
|Contact: Fiona Campbell, MD 01132-064-996|
|Contact: Emily Metcalfe 0113 206 4996 ext 64996 firstname.lastname@example.org|
|Study Chair:||Roman Hovorka, PhD||University of Cambridge|
|Principal Investigator:||Carlo Acerini, MD||University of Cambridge|
|Principal Investigator:||Fiona Campbell, MD||The Leeds Teaching Hospitals NHS Trust|
|Principal Investigator:||Bruce Buckingham, MD||Stanford University|
|Principal Investigator:||Stuart Weinzimer, MD||Yale University|
|Principal Investigator:||Linda DiMeglio, MD||Indiana University|
|Principal Investigator:||Paul Wadwa, MD||University of Colorado Denver School of Medicine Barbara Davis Center|
|Principal Investigator:||Korey Hood, PhD||Stanford University|
|Principal Investigator:||Dana Goldman, PhD||University of Southern California|
|Principal Investigator:||Nikki C Davis, MD||Southampton Children's Hospital|
|Principal Investigator:||Louise Denvir, MD||Nottingham Children's Hospital|
|Principal Investigator:||Nelly Mauras, MD||Nemours Children's Health System|