Closing the Loop in Children and Adolescents With Type 1 Diabetes in the Home Setting (APCam08)
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).
|Diabetes Mellitus Diabetes Mellitus, Type 1 Glucose Metabolism Disorders Endocrine System Diseases Autoimmune Diseases||Device: Overnight closed-loop Device: Real-time CGM alone||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: No masking
Primary Purpose: Treatment
|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|
- 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 ]
- 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 ]
- Safety evaluation [ Time Frame: 3 month home study period ]Safety evaluation will comprise number of episodes of severe hypoglycaemia as well as the number of subjects experiencing severe hypoglycaemia and other adverse events, including ketone-positive hyperglycaemia. Subjects will be asked to measure blood or urine ketone levels on waking in the morning if their finger prick glucose is above 14mmol/l, as part of the safety evaluation for hyperglycaemia.
- Utility Evaluation [ Time Frame: 3 month home study period ]Utility evaluation is the frequency and duration of use of the closed-loop system combined with CGM as compared to the use of real time CGM alone, and the subjects' response in terms of life-style change, daily diabetes management and fear of hypoglycaemia, as evaluated by questionnaires and a semi-structured qualitative interview.
|Study Start Date:||December 2013|
|Study Completion Date:||May 2015|
|Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: Overnight closed-loop combined with CGM
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.
Device: Overnight closed-loop
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.
Active Comparator: Real-time CGM alone
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)
Device: Real-time CGM alone
Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01778348
|University of Cambridge|
|Cambridge, United Kingdom, CB2 0QQ|
|Leeds Teaching Hospitals|
|Leeds, United Kingdom, LS9 7TF|
|University College London Hospital|
|London, United Kingdom, NW1 2BU|
|Study Director:||Roman Hovorka, PhD||University of Cambridge|
|Principal Investigator:||David Dunger, MD, FRCPCH||University of Cambridge|
|Principal Investigator:||Peter Hindmarsh, MD, FRCPCH||University College London Hospitals|
|Principal Investigator:||Fiona Campbell, MD, FRCPCH||Leeds Teaching Hospitals|