Diabetes MellitusPhase 2APCam08NCT01778348
Closing the Loop in Children and Adolescents With Type 1 Diabetes in the Home Setting
A Phase 2 study testing Overnight closed-loop and Real-time CGM alone in people with Diabetes Mellitus and Diabetes Mellitus, Type 1, run by University of Cambridge at 3 sites in United Kingdom.
Trial summary
Type 1 diabetes (T1D) is one of the most common chronic childhood diseases requiring lifelong insulin therapy. Children and adolescents with T1D need regular insulin injections or the continuous insulin delivery using an insulin pump in order to keep blood glucose levels normal. 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?
- Overnight closed-loop and Real-time CGM alone
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Dec 2013to May 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- The subject is between 6 and 18 years of age (inclusive)
- The subject has type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative
- The subject will have been an insulin pump user for at least 3 months, with good knowledge of insulin self-adjustment as judged by the investigator
- The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements taken every day
- HbA1c ≤ 10 % based on analysis from central laboratory or equivalent
- The subject is literate in English
Who cannot join
- Non-type 1 diabetes mellitus including those secondary to chronic disease
- Untreated celiac disease
- 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
- 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 against insulin
- Subjects with clinical significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator
Show all 12Show fewer
- Total daily insulin dose ≤ 2 IU/kg/day
- Total daily insulin dose < 10 IU/day
- Pregnancy, planned pregnancy, or breast feeding
- Severe visual impairment
- Severe hearing impairment
- Subjects using implanted internal pace-maker
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
University of Cambridge
Cambridge, CB2 0QQ
Leeds Teaching Hospitals
Leeds, LS9 7TF
University College London Hospital
London, NW1 2BU
About this study
Official title: An Open-label, Three-centre, Randomised, Two-period, Crossover Study to Assess the Efficacy, Safety and Utility of Overnight Closed-loop in Comparison With CGM Alone in the Home Setting in Children and Adolescents With Type 1 Diabetes
Type 1 diabetes (T1D) is one of the most common chronic childhood diseases requiring lifelong insulin therapy. Children and adolescents with T1D need regular insulin injections or the continuous insulin delivery using an insulin pump in order to keep blood glucose levels normal. We know that keeping blood sugars in the normal range will help prevent longterm diabetes-related complications involving the eyes, kidneys and heart. However, achieving treatment goals can be very difficult as the tighter we try to control blood glucose levels, the greater the risk to develop symptoms and signs of low glucose levels (hypoglycaemia). This is a particular problem at night and one solution is to develop a system whereby the amount of insulin injected is controlled by a computer and is very closely matched to the blood sugar levels on a continuous basis. This can be achieved by what is known as a "closed-loop system" where a small glucose sensor placed under the skin communicates with a computer containing an algorithm that drives an insulin pump. We have been testing such a system in Cambridge over the last five years in children and have found that this system is effective at maintaining tight glucose control and preventing nocturnal hypoglycaemia. More recently the system has been tested in real life conditions in the home setting for three weeks during a pilot single-centre study.
The next step is to extend the evaluation of closed-loop over a prolonged period of three months. In the present study we are planning to study 24 young people aged 6-18 years on insulin pump therapy. During three months glucose will be controlled by the computer and during the other three months the subjects will make their own adjustments to the insulin therapy using real-time continuous glucose monitoring.
We aim to determine the effect of the computer algorithm in keeping glucose levels between 3.9 and 8 mmol/L (normal levels). Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes. Participants' response to the use of the system in terms of lifestyle change, daily diabetes management and fear of hypoglycaemia will be assessed. We will also test for longer term glucose control by measuring glycated haemoglobin (HbA1c).
Read the detailed description
Purpose of the study
The purpose of this research is to evaluate the efficacy, safety and utility of the overnight automated closed-loop system in the home setting on consecutive nights over a 3-month period, as compared to the use of real-time continuous glucose monitoring (CGM) alone.
Design
The study is designed in the form of an open-label, cross-over study and it involves two 3-month-long home studies during which overnight glucose levels will be controlled either by a closed-loop (CL) system combined with a real-time continuous subcutaneous glucose monitoring (CGM) or by real-time continuous glucose monitoring alone, in random order.
The study will take place within the home setting where, initially, overnight supervision of the closed-loop system will be undertaken by a research nurse either at home or at an in-patient facility.
Three UK centres will be involved in the study: Addenbrooke's Hospital, Cambridge, University College London Hospital (UCLH), London, Leeds Teaching Hospitals, Leeds
Population
A total of 30 children and adolescents with T1D between 6 and 18 years of age on insulin pump therapy will be recruited from the Paediatric Diabetes Outpatient Clinics at the three investigation centres to allow for 24 evaluable subjects. Each investigation centre will recruit at least three subjects to achieve balanced representation of study population.
Potential participants will be identified by their treating clinicians and invited to contact the research team. They will be sent the study information leaflets and an invitation to join the study by the research team. They will have the opportunity to read and discuss the information. If they agree to participate in the study, informed consent and/or assent will be taken by a member of the research team who has a good working knowledge of the aims and practicalities of the study. The person taking consent will use language that is easy to understand and free from medical jargon.
Experimental Procedures
The study will consist of up to 10 visits, including two study periods (closed-loop vs. conventional pump therapy + continuous glucose monitoring). The study periods will last 3 months each. The order of the two interventions will be random.
Once the subjects have agreed to participate in the study, they will be invited for the recruitment visit, when participants' body weight and height, demographics, medical and diabetes history, and their previous days insulin therapy will be recorded. Urine pregnancy test will also be performed in females of children-bearing age.
Once consent has been obtained and if all the inclusion and exclusion criteria are met the subject will be included in the study and allocated a sequential subject number.
Blood samples will be taken for the baseline measurement of random C-peptide, glucose and HbA1c. Eligible subjects will also undergo a baseline evaluation where a blood sample for renal, liver, thyroid function, full blood count and anti-transglutaminase antibodies with IgA levels will be taken (if not done in the previous 3 months).
Validated questionnaires will be distributed to assess both the user friendliness of the devices used by study participants and fear of hypoglycaemia before entering the study. Study participants will also be invited to participate in a semi-structured qualitative interview conducted by trained staff, which will occur face-to-face or via telephone, within 2-4 weeks (during the training period), to determine their expectations of the diabetes treatments to be used in the study.
All eligible subjects who will have signed informed consent will be invited to a training session on the use of the devices which will be employed in the study.
- Two to four weeks prior to the first study night the subjects will be switched from their regular insulin pump to the study subcutaneous insulin infusion pump for the period of the study. Local diabetes clinic guidelines for switching insulin pumps will be followed. Subjects will be given training on the functionality of the pump by the research team and standard operational procedures, as well as the pump user manual, will be provided. The research and paediatric diabetes team will be available by telephone to assist with any concerns that the subjects may have regarding the pump.
- A training session on Continuous Glucose Monitoring (CGM) will take place about two to four weeks before the study starts. Subjects will be trained on the use of the study CGM system. Subjects will be trained at home/clinic by the research nurse to insert a subcutaneous glucose sensor and will be provided with the study CGM system to wear at home for at least three consecutive 5-day-sensor sessions (at least 12 days of use) or until subjects become confident with the device, namely with the performance of sensor insertion and calibrations. During the two to four week training period the CGM display may be masked so that subjects will not be able to see their glucose values. For subjects who use CGM as part of their normal diabetes care, the CGM display will not be masked during this training period. At the end of the training period the sensor data will be downloaded by the research team and will be used to optimise insulin therapy prior to the start of the study. This will be done in collaboration with the paediatrics diabetes team. The CGM readings recorded during this training period will used to assess baseline glucose control.
At the end of the training session, a competency assessment tool will be used to evaluate subjects' competency in the use of both devices. Subjects' compliance in diabetes management will also be evaluated in terms of time wearing the continuous glucose monitoring device. A minimum of 12 days of continuous glucose monitor readings should be recorded over the time of use of the device. Competency and compliance evaluations will determine participants' eligibility before randomisation.
Eligible subjects, who have completed the training session on the use of both the study subcutaneous insulin pump and the study CGM device and gained confidence in the use of both devices as assessed by the research team, will be randomised to one of the 2 intervention arms:
- Real-time CGM + overnight CL
- Real-time CGM alone Three to four weeks after the completion of each intervention arm, subjects will cross over to alternative intervention: those who were allocated to the CGM+CL intervention will be switched to CGM alone intervention, whereas those who completed the CGM alone intervention will be allocated to the CGM+CL intervention. During this three-to-four-weeks wash out period, real-time CGM may be used.
Additional training on the use of real-time CGM will be provided at the beginning of the first intervention arm. This involves training on how to interpret the data displayed on the real-time CGM device screen and how to perform insulin therapy adjustments according to glucose reports. Written guidelines on the use of both real-time and retrospective information will be provided to all subjects.
At the beginning of the closed-loop intervention, subjects will be provided with specific training on the use of the closed-loop system. Closed-loop training will be carried out in two consecutive stages:
- Supervised Closed Loop: the closed-loop system will be started in the evening or at bedtime and will remain in operation until the following morning. Each subject will be supervised in starting the closed-loop system by the research nurse/doctor for one night at home or at an in-patient facility, with the option of a second supervised night at the start of the closed-loop intervention, until the subject is confident to use the equipment. For subjects who were supervised in using the closed-loop system at the in-patient facility, the research nurse/clinician may provide assistance and supervision in setting up the closed-loop system for the first night at home.
- Unsupervised Closed Loop: Subjects will use the closed-loop system overnight at home for a total duration of 12 weeks. The subcutaneous CGM sensor will be replaced every 5 days by the subjects. Support and telephone advice will be provided by the research team for the duration of the study to deal with any concerns that may arise with the use of the closed-loop system components.
Cross-over procedures:
Having completed the first intervention arm, all subjects will cross over to the other intervention arm after a wash-out period of three to four weeks. Blood sampling for the determination of HbA1c will be taken to investigate any changes in metabolic control. Validated questionnaires will be distributed to evaluate the impact and satisfaction as well as the user friendliness of the devices employed in the completed arm of the study. A questionnaire evaluating fear of hypoglycaemia will also be distributed to both parents and children. Study participants will be invited to participate in a semi-structured qualitative interview conducted by trained staff within 0-4 weeks of completing the Closed Loop intervention arm, including their views on the diabetes treatment experienced. The second intervention treatment arm will start three to four weeks after the end of the first arm. In between the two intervention arms, subjects will resume their usual insulin regimen, using either the study insulin pump or usual patient's insulin pump. Real-time CGM may be used as part of their standard diabetes management.
End of study:
Having completed the second intervention arm of the study, subjects will revert to their conventional insulin pump therapy by switching to the insulin pump they were using before entering the study. Blood sampling for the determination of HbA1c will be taken to investigate any changes in metabolic control. Validated questionnaires will be distributed to evaluate the impact and satisfaction as well as the user friendliness of the devices employed in the completed arm of the study.
- Conditions
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Endocrine System Diseases, Autoimmune Diseases
- Being tested
- Overnight closed-loop, Real-time CGM alone
- Keywords
- Type 1 diabetes, Closed-loop glucose control, Artificial Pancreas, Continuous subcutaneous insulin infusion, Continuous glucose monitoring
- 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.
Overnight closed-loopDevice
The closed-loop system is purpose-built and comprises a hand-held computer containing a model predictive control (MPC) based glucose control algorithm and communicating with the CGM device and the insulin pump.
Real-time CGM aloneDevice
Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)
| Study group | Role | What they receive |
|---|---|---|
| Overnight closed-loop combined with CGM | Experimental | Glucose level is controlled by the automated closed loop glucose control system. After initial training with the closed-loop system devices, subjects will use the closed-loop system overnight at home for a total duration of 12 weeks. Receives: Device: Overnight closed-loop |
| Real-time CGM alone | Active comparator | The subjects will use the study CGM alone at home for the period of 12 weeks. Glucose level will be controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM) Receives: Device: Real-time CGM alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time spent overnight in the target glucose range (3.9 to 8.0 mmol/l), as assessed by adjusted continuous subcutaneous glucose monitoring (CGM)
Measured: 3 month home study period
Secondary outcomes (12)
The proportion of nights when glucose levels drop below 3.5 mmol/l for 20 minutes or longer, as recorded by CGM
Measured: 3 month home study period
Time spent above and below the target glucose (3.9 to 8.0 mmol/l) based on CGM.
Measured: 3 month home study period
The time with glucose levels in the significant hyperglycaemia range (glucose levels > 16.7 mmol/l) as recorded by CGM
Measured: 3 month home study period
Metabolic control assessed by HbA1c
Measured: 3 month home study period
Average and standard deviation of glucose levels, as recorded by CGM
Measured: 3 month home study period
The time with glucose levels < 3.5 mmol/l as recorded by CGM.
Measured: 3 month home study period
The time with glucose levels in the widened target range, as recorded by CGM (glucose levels ≥ 3.9mmol/l to ≤ 10.0mmol/l )
Measured: 3 month home study period
Low Blood Glucose Index (LBGI), as recorded by CGM.
Measured: 3 month home study period
Standard deviation of the glucose rate of change, as recorded by CGM.
Measured: 3 month home study period
Overnight insulin dose
Measured: 3 month home study period
Total daily insulin dose
Measured: 3 month home study period
Episodes of symptomatic hypoglycaemia
Measured: 3 month home study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2013 (estimated)
- Study startDec 2013
- Primary completionMar 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, University College London Hospitals, The Leeds Teaching Hospitals NHS Trust
- Responsible party
- Principal investigator, Dr Roman Hovorka, University of Cambridge
- Investigators
- Roman Hovorka, PhD, Study director, University of CambridgeDavid Dunger, MD, FRCPCH, Principal investigator, University of CambridgePeter Hindmarsh, MD, FRCPCH, Principal investigator, University College London HospitalsFiona Campbell, MD, FRCPCH, Principal investigator, Leeds Teaching Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01778348
- Sponsor's protocol ID
- APCam08
- Acronym
- APCam08
- Status last verified
- Feb 2017
- First submitted
- 25 Jan 2013
- Last updated
- 3 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Elleri D, Allen JM, Biagioni M, Kumareswaran K, Leelarathna L, Caldwell K, Nodale M, Wilinska ME, Acerini CL, Dunger DB, Hovorka R. Evaluation of a portable ambulatory prototype for automated overnight closed-loop insulin delivery in young people with type 1 diabetes. Pediatr Diabetes. 2012 Sep;13(6):449-53. doi: 10.1111/j.1399-5448.2012.00903.x. Epub 2012 Jul 23.
PubMed 22817340Kumareswaran K, Elleri D, Allen JM, Harris J, Xing D, Kollman C, Nodale M, Murphy HR, Amiel SA, Heller SR, Wilinska ME, Acerini CL, Evans ML, Dunger DB, Hovorka R. Meta-analysis of overnight closed-loop randomized studies in children and adults with type 1 diabetes: the Cambridge cohort. J Diabetes Sci Technol. 2011 Nov 1;5(6):1352-62. doi: 10.1177/193229681100500606.
PubMed 22226252Hovorka R, Kumareswaran K, Harris J, Allen JM, Elleri D, Xing D, Kollman C, Nodale M, Murphy HR, Dunger DB, Amiel SA, Heller SR, Wilinska ME, Evans ML. Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies. BMJ. 2011 Apr 13;342:d1855. doi: 10.1136/bmj.d1855.
PubMed 21493665Hovorka R, Allen JM, Elleri D, Chassin LJ, Harris J, Xing D, Kollman C, Hovorka T, Larsen AM, Nodale M, De Palma A, Wilinska ME, Acerini CL, Dunger DB. Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet. 2010 Feb 27;375(9716):743-51. doi: 10.1016/S0140-6736(09)61998-X. Epub 2010 Feb 4.
PubMed 20138357Thabit 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; New Collective Author. 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
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Three-centre, Randomised, Two-period, Crossover Study to Assess the Efficacy, Safety and Utility of Overnight Closed-loop in Comparison With CGM Alone in the Home Setting in Children and Adolescents With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT01778348
- Acronym / sponsor ID
- APCam08 / APCam08
- Conditions
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Endocrine System Diseases, Autoimmune Diseases
- Keywords
- Type 1 diabetes, Closed-loop glucose control, Artificial Pancreas, Continuous subcutaneous insulin infusion, Continuous glucose monitoring
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, University College London Hospitals, The Leeds Teaching Hospitals NHS Trust
- Study start
- Dec 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 29 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Type 1 diabetes (T1D) is one of the most common chronic childhood diseases requiring lifelong insulin therapy. Children and adolescents with T1D need regular insulin injections or the continuous insulin delivery using an insulin pump in order to keep blood glucose levels normal. We know that keeping blood sugars in the normal range will help prevent longterm diabetes-related complications involving the eyes, kidneys and heart. However, achieving treatment goals can be very difficult as the tighter we try to control blood glucose levels, the greater the risk to develop symptoms and signs of low glucose levels (hypoglycaemia). This is a particular problem at night and one solution is to develop a system whereby the amount of insulin injected is controlled by a computer and is very closely matched to the blood sugar levels on a continuous basis. This can be achieved by what is known as a "closed-loop system" where a small glucose sensor placed under the skin communicates with a computer containing an algorithm that drives an insulin pump. We have been testing such a system in Cambridge over the last five years in children and have found that this system is effective at maintaining tight glucose control and preventing nocturnal hypoglycaemia. More recently the system has been tested in real life conditions in the home setting for three weeks during a pilot single-centre study.
The next step is to extend the evaluation of closed-loop over a prolonged period of three months. In the present study we are planning to study 24 young people aged 6-18 years on insulin pump therapy. During three months glucose will be controlled by the computer and during the other three months the subjects will make their own adjustments to the insulin therapy using real-time continuous glucose monitoring.
We aim to determine the effect of the computer algorithm in keeping glucose levels between 3.9 and 8 mmol/L (normal levels). Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes. Participants' response to the use of the system in terms of lifestyle change, daily diabetes management and fear of hypoglycaemia will be assessed. We will also test for longer term glucose control by measuring glycated haemoglobin (HbA1c).
Detailed description
Purpose of the study
The purpose of this research is to evaluate the efficacy, safety and utility of the overnight automated closed-loop system in the home setting on consecutive nights over a 3-month period, as compared to the use of real-time continuous glucose monitoring (CGM) alone.
Design
The study is designed in the form of an open-label, cross-over study and it involves two 3-month-long home studies during which overnight glucose levels will be controlled either by a closed-loop (CL) system combined with a real-time continuous subcutaneous glucose monitoring (CGM) or by real-time continuous glucose monitoring alone, in random order.
The study will take place within the home setting where, initially, overnight supervision of the closed-loop system will be undertaken by a research nurse either at home or at an in-patient facility.
Three UK centres will be involved in the study: Addenbrooke's Hospital, Cambridge, University College London Hospital (UCLH), London, Leeds Teaching Hospitals, Leeds
Population
A total of 30 children and adolescents with T1D between 6 and 18 years of age on insulin pump therapy will be recruited from the Paediatric Diabetes Outpatient Clinics at the three investigation centres to allow for 24 evaluable subjects. Each investigation centre will recruit at least three subjects to achieve balanced representation of study population.
Potential participants will be identified by their treating clinicians and invited to contact the research team. They will be sent the study information leaflets and an invitation to join the study by the research team. They will have the opportunity to read and discuss the information. If they agree to participate in the study, informed consent and/or assent will be taken by a member of the research team who has a good working knowledge of the aims and practicalities of the study. The person taking consent will use language that is easy to understand and free from medical jargon.
Experimental Procedures
The study will consist of up to 10 visits, including two study periods (closed-loop vs. conventional pump therapy + continuous glucose monitoring). The study periods will last 3 months each. The order of the two interventions will be random.
Once the subjects have agreed to participate in the study, they will be invited for the recruitment visit, when participants' body weight and height, demographics, medical and diabetes history, and their previous days insulin therapy will be recorded. Urine pregnancy test will also be performed in females of children-bearing age.
Once consent has been obtained and if all the inclusion and exclusion criteria are met the subject will be included in the study and allocated a sequential subject number.
Blood samples will be taken for the baseline measurement of random C-peptide, glucose and HbA1c. Eligible subjects will also undergo a baseline evaluation where a blood sample for renal, liver, thyroid function, full blood count and anti-transglutaminase antibodies with IgA levels will be taken (if not done in the previous 3 months).
Validated questionnaires will be distributed to assess both the user friendliness of the devices used by study participants and fear of hypoglycaemia before entering the study. Study participants will also be invited to participate in a semi-structured qualitative interview conducted by trained staff, which will occur face-to-face or via telephone, within 2-4 weeks (during the training period), to determine their expectations of the diabetes treatments to be used in the study.
All eligible subjects who will have signed informed consent will be invited to a training session on the use of the devices which will be employed in the study.
- Two to four weeks prior to the first study night the subjects will be switched from their regular insulin pump to the study subcutaneous insulin infusion pump for the period of the study. Local diabetes clinic guidelines for switching insulin pumps will be followed. Subjects will be given training on the functionality of the pump by the research team and standard operational procedures, as well as the pump user manual, will be provided. The research and paediatric diabetes team will be available by telephone to assist with any concerns that the subjects may have regarding the pump.
- A training session on Continuous Glucose Monitoring (CGM) will take place about two to four weeks before the study starts. Subjects will be trained on the use of the study CGM system. Subjects will be trained at home/clinic by the research nurse to insert a subcutaneous glucose sensor and will be provided with the study CGM system to wear at home for at least three consecutive 5-day-sensor sessions (at least 12 days of use) or until subjects become confident with the device, namely with the performance of sensor insertion and calibrations. During the two to four week training period the CGM display may be masked so that subjects will not be able to see their glucose values. For subjects who use CGM as part of their normal diabetes care, the CGM display will not be masked during this training period. At the end of the training period the sensor data will be downloaded by the research team and will be used to optimise insulin therapy prior to the start of the study. This will be done in collaboration with the paediatrics diabetes team. The CGM readings recorded during this training period will used to assess baseline glucose control.
At the end of the training session, a competency assessment tool will be used to evaluate subjects' competency in the use of both devices. Subjects' compliance in diabetes management will also be evaluated in terms of time wearing the continuous glucose monitoring device. A minimum of 12 days of continuous glucose monitor readings should be recorded over the time of use of the device. Competency and compliance evaluations will determine participants' eligibility before randomisation.
Eligible subjects, who have completed the training session on the use of both the study subcutaneous insulin pump and the study CGM device and gained confidence in the use of both devices as assessed by the research team, will be randomised to one of the 2 intervention arms:
- Real-time CGM + overnight CL
- Real-time CGM alone Three to four weeks after the completion of each intervention arm, subjects will cross over to alternative intervention: those who were allocated to the CGM+CL intervention will be switched to CGM alone intervention, whereas those who completed the CGM alone intervention will be allocated to the CGM+CL intervention. During this three-to-four-weeks wash out period, real-time CGM may be used.
Additional training on the use of real-time CGM will be provided at the beginning of the first intervention arm. This involves training on how to interpret the data displayed on the real-time CGM device screen and how to perform insulin therapy adjustments according to glucose reports. Written guidelines on the use of both real-time and retrospective information will be provided to all subjects.
At the beginning of the closed-loop intervention, subjects will be provided with specific training on the use of the closed-loop system. Closed-loop training will be carried out in two consecutive stages:
- Supervised Closed Loop: the closed-loop system will be started in the evening or at bedtime and will remain in operation until the following morning. Each subject will be supervised in starting the closed-loop system by the research nurse/doctor for one night at home or at an in-patient facility, with the option of a second supervised night at the start of the closed-loop intervention, until the subject is confident to use the equipment. For subjects who were supervised in using the closed-loop system at the in-patient facility, the research nurse/clinician may provide assistance and supervision in setting up the closed-loop system for the first night at home.
- Unsupervised Closed Loop: Subjects will use the closed-loop system overnight at home for a total duration of 12 weeks. The subcutaneous CGM sensor will be replaced every 5 days by the subjects. Support and telephone advice will be provided by the research team for the duration of the study to deal with any concerns that may arise with the use of the closed-loop system components.
Cross-over procedures:
Having completed the first intervention arm, all subjects will cross over to the other intervention arm after a wash-out period of three to four weeks. Blood sampling for the determination of HbA1c will be taken to investigate any changes in metabolic control. Validated questionnaires will be distributed to evaluate the impact and satisfaction as well as the user friendliness of the devices employed in the completed arm of the study. A questionnaire evaluating fear of hypoglycaemia will also be distributed to both parents and children. Study participants will be invited to participate in a semi-structured qualitative interview conducted by trained staff within 0-4 weeks of completing the Closed Loop intervention arm, including their views on the diabetes treatment experienced. The second intervention treatment arm will start three to four weeks after the end of the first arm. In between the two intervention arms, subjects will resume their usual insulin regimen, using either the study insulin pump or usual patient's insulin pump. Real-time CGM may be used as part of their standard diabetes management.
End of study:
Having completed the second intervention arm of the study, subjects will revert to their conventional insulin pump therapy by switching to the insulin pump they were using before entering the study. Blood sampling for the determination of HbA1c will be taken to investigate any changes in metabolic control. Validated questionnaires will be distributed to evaluate the impact and satisfaction as well as the user friendliness of the devices employed in the completed arm of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Overnight closed-loop combined with CGM | Experimental | Device: Overnight closed-loopGlucose level is controlled by the automated closed loop glucose control system. After initial training with the closed-loop system devices, subjects will use the closed-loop system overnight at home for a total duration of 12 weeks. |
| Real-time CGM alone | Active comparator | Device: Real-time CGM aloneThe subjects will use the study CGM alone at home for the period of 12 weeks. Glucose level will be controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM) |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- The subject is between 6 and 18 years of age (inclusive)
- The subject has type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative
- The subject will have been an insulin pump user for at least 3 months, with good knowledge of insulin self-adjustment as judged by the investigator
- The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements taken every day
- HbA1c ≤ 10 % based on analysis from central laboratory or equivalent
Key exclusion criteria (12 listed)
- Non-type 1 diabetes mellitus including those secondary to chronic disease
- Untreated celiac disease
- 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
- 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 against insulin
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 |
|---|---|---|
| Overnight closed-loopThe closed-loop system is purpose-built and comprises a hand-held computer containing a model predictive control (MPC) based glucose control algorithm and communicating with the CGM device and the insulin pump. | Device | Overnight closed-loop combined with CGM |
| Real-time CGM aloneSubject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM) | Device | Real-time CGM alone |
Primary outcome
Time spent overnight in the target glucose range (3.9 to 8.0 mmol/l), as assessed by adjusted continuous subcutaneous glucose monitoring (CGM)
Time frame: 3 month home study period
12 secondary outcomes
The proportion of nights when glucose levels drop below 3.5 mmol/l for 20 minutes or longer, as recorded by CGM
Time frame: 3 month home study period
Time spent above and below the target glucose (3.9 to 8.0 mmol/l) based on CGM.
Time frame: 3 month home study period
The time with glucose levels in the significant hyperglycaemia range (glucose levels > 16.7 mmol/l) as recorded by CGM
Time frame: 3 month home study period
Metabolic control assessed by HbA1c
Time frame: 3 month home study period
Average and standard deviation of glucose levels, as recorded by CGM
Time frame: 3 month home study period
The time with glucose levels < 3.5 mmol/l as recorded by CGM.
Time frame: 3 month home study period
The time with glucose levels in the widened target range, as recorded by CGM (glucose levels ≥ 3.9mmol/l to ≤ 10.0mmol/l )
Time frame: 3 month home study period
Low Blood Glucose Index (LBGI), as recorded by CGM.
Time frame: 3 month home study period
Standard deviation of the glucose rate of change, as recorded by CGM.
Time frame: 3 month home study period
Overnight insulin dose
Time frame: 3 month home study period
Total daily insulin dose
Time frame: 3 month home study period
Episodes of symptomatic hypoglycaemia
Time frame: 3 month home study period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2017.
- Background: PubMed 22817340Elleri D, Allen JM, Biagioni M, Kumareswaran K, Leelarathna L, Caldwell K, Nodale M, Wilinska ME, Acerini CL, Dunger DB, Hovorka R. Evaluation of a portable ambulatory prototype for automated overnight closed-loop insulin delivery in young people with type 1 diabetes. Pediatr Diabetes. 2012 Sep;13(6):449-53. doi: 10.1111/j.1399-5448.2012.00903.x. Epub 2012 Jul 23.
- Background: PubMed 22226252Kumareswaran K, Elleri D, Allen JM, Harris J, Xing D, Kollman C, Nodale M, Murphy HR, Amiel SA, Heller SR, Wilinska ME, Acerini CL, Evans ML, Dunger DB, Hovorka R. Meta-analysis of overnight closed-loop randomized studies in children and adults with type 1 diabetes: the Cambridge cohort. J Diabetes Sci Technol. 2011 Nov 1;5(6):1352-62. doi: 10.1177/193229681100500606.
- Background: PubMed 21493665Hovorka R, Kumareswaran K, Harris J, Allen JM, Elleri D, Xing D, Kollman C, Nodale M, Murphy HR, Dunger DB, Amiel SA, Heller SR, Wilinska ME, Evans ML. Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies. BMJ. 2011 Apr 13;342:d1855. doi: 10.1136/bmj.d1855.
- Background: PubMed 20138357Hovorka R, Allen JM, Elleri D, Chassin LJ, Harris J, Xing D, Kollman C, Hovorka T, Larsen AM, Nodale M, De Palma A, Wilinska ME, Acerini CL, Dunger DB. Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet. 2010 Feb 27;375(9716):743-51. doi: 10.1016/S0140-6736(09)61998-X. Epub 2010 Feb 4.
- Results publication: PubMed 26379095Thabit 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; New Collective Author. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roman Hovorka, PhD study director
University of Cambridge
David Dunger, MD, FRCPCH principal investigator
University of Cambridge
Peter Hindmarsh, MD, FRCPCH principal investigator
University College London Hospitals
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Overnight closed-loop and Real-time CGM alone in people with Diabetes Mellitus and Diabetes Mellitus, Type 1, run by University of Cambridge at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 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 3 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time spent overnight in the target glucose range (3.9 to 8.0 mmol/l), as assessed by adjusted continuous subcutaneous glucose monitoring (CGM) (time frame: 3 month home study period). 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 NCT01778348, which also lists 5 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 3 Mar 2017.