Closing the Loop in Children and Adolescents With Type 1 Diabetes in the Home Setting (APCam08)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Cambridge
Sponsor:
Collaborators:
Cambridge University Hospitals NHS Foundation Trust
University College London Hospitals
The Leeds Teaching Hospitals NHS Trust
Information provided by (Responsible Party):
Dr Roman Hovorka, University of Cambridge
ClinicalTrials.gov Identifier:
NCT01778348
First received: January 25, 2013
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by University of Cambridge:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Metabolic control assessed by HbA1c [ Time Frame: 3 month home study period ] [ Designated as safety issue: No ]
  • Average and standard deviation of glucose levels, as recorded by CGM [ Time Frame: 3 month home study period ] [ Designated as safety issue: No ]
  • The time with glucose levels < 3.5 mmol/l as recorded by CGM. [ Time Frame: 3 month home study period ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Low Blood Glucose Index (LBGI), as recorded by CGM. [ Time Frame: 3 month home study period ] [ Designated as safety issue: No ]
  • Standard deviation of the glucose rate of change, as recorded by CGM. [ Time Frame: 3 month home study period ] [ Designated as safety issue: No ]
  • Overnight insulin dose [ Time Frame: 3 month home study period ] [ Designated as safety issue: No ]
  • Total daily insulin dose [ Time Frame: 3 month home study period ] [ Designated as safety issue: No ]
  • Episodes of symptomatic hypoglycaemia [ Time Frame: 3 month home study period ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Safety evaluation [ Time Frame: 3 month home study period ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 24
Study Start Date: December 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01778348

Contacts
Contact: Martin Tauschmann, MD +44 1223 769 066 mt614@medschl.cam.ac.uk

Locations
United Kingdom
University of Cambridge Recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Martin Tauschmann, MD    +44 (0)1224 769066    mt614@medschl.cam.ac.uk   
Principal Investigator: David Dunger, MD, FRCPCH         
Leeds Teaching Hospitals Not yet recruiting
Leeds, United Kingdom, LS9 7TF
Contact: Fiona Campbell, MD, FRCPCH    +44 (0)1132065924    Fiona.Campbell@leedsth.nhs.uk   
Principal Investigator: Fiona Campbell, MD, FRCPCH         
University College London Hospital Not yet recruiting
London, United Kingdom, NW1 2BU
Contact: Peter Hindmarsh, MD, FRCPCH    +44 (0)2034479221    peter.hindmarsh@nhs.net   
Principal Investigator: Peter Hindmarsh, MD, FRCPCH         
Sponsors and Collaborators
University of Cambridge
Cambridge University Hospitals NHS Foundation Trust
University College London Hospitals
The Leeds Teaching Hospitals NHS Trust
Investigators
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
  More Information

Publications:
Responsible Party: Dr Roman Hovorka, Director of Research, University of Cambridge
ClinicalTrials.gov Identifier: NCT01778348     History of Changes
Other Study ID Numbers: APCam08
Study First Received: January 25, 2013
Last Updated: April 30, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Cambridge:
Type 1 diabetes
Closed-loop glucose control
Artificial Pancreas
Continuous subcutaneous insulin infusion
Continuous glucose monitoring

Additional relevant MeSH terms:
Autoimmune Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 1
Endocrine System Diseases
Metabolic Diseases
Glucose Metabolism Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 24, 2014