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

NCT01778348 | Completed Phase 2 DMC

• 1 other identifier: APCam08
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief 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. 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).

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

Outcome Measures

Primary Outcomes (1)

• Time spent overnight in the target glucose range (3.9 to 8.0 mmol/l), as assessed by adjusted continuous subcutaneous glucose monitoring (CGM)

  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

  3 month home study period

• Time spent above and below the target glucose (3.9 to 8.0 mmol/l) based on CGM.

  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

  3 month home study period

• Metabolic control assessed by HbA1c

  3 month home study period

• Average and standard deviation of glucose levels, as recorded by CGM

  3 month home study period

Other Outcomes (2)

• Safety evaluation

  3 month home study period

• Utility Evaluation

  3 month home study period

Study Arms (2)

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.

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)

Device: Real-time CGM alone

Interventions

Overnight closed-loop DEVICE

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.

Overnight closed-loop combined with CGM

Real-time CGM alone DEVICE

Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)

Real-time CGM alone

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Cambridge: lead
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• University College London Hospitals: collaborator
• The Leeds Teaching Hospitals NHS Trust: collaborator

Study Sites (3)

University of Cambridge

Cambridge, CB2 0QQ, United Kingdom

Location

Leeds Teaching Hospitals

Leeds, LS9 7TF, United Kingdom

Location

University College London Hospital

London, NW1 2BU, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 22817340 BACKGROUND

• Kumareswaran 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.

  PMID: 22226252 BACKGROUND

• Hovorka 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.

  PMID: 21493665 BACKGROUND

• Hovorka 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.

  PMID: 20138357 BACKGROUND

• Thabit 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. 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.

  PMID: 26379095 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Endocrine System Diseases; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Immune System Diseases

Study Officials

• Roman Hovorka, PhD

  University of Cambridge

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research

Study Record Dates

• First Submitted: January 25, 2013
• First Posted: January 29, 2013
• Study Start: December 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: May 1, 2015
• Last Updated: March 3, 2017

Record last verified: 2017-02

Locations

GB (3)