Closing the Loop 24/7 in Adolescents With Type 1 Diabetes

NCT01873066 | Completed DMC

• 1 other identifier: DAN04
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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 long-term diabetes-related complications involving the eyes, kidneys and heart. However, achieving treatment goals can be very difficult particularly due to the risk of low glucose levels (hypoglycaemia). One solution is to use a system where the amount of insulin injected closely matches 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 a subcutaneous 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, and superior to usual insulin pump therapy, at maintaining tight glucose control. More recently the system has been tested overnight, in the home setting, for three weeks in adolescents during a pilot single-centre study. The next step is to evaluate use of the closed loop system day and night over a period of 7 days (phase 1) and 21 days (phase 2) in adolescents with type 1 diabetes. In the present study we are planning to study 24 (12 phase 1 ans 12 phase 2) young people aged 10-18 years on insulin pump therapy. This study will involve two 7 (phase 1) and 21 (phase 2) day home study periods, during which glucose levels will be controlled either by an automated closed-loop system or by subjects usual insulin pump therapy combined with continuous glucose monitoring alone in random order. Prior to the closed-loop study period, there will be a training period in the clinical research facility, which will allow participants to familiarise themselves with the closed-loop system before going home. We aim to to determine the effect of the closed-loop computer algorithm in keeping glucose levels between 3.9 and 10.0 mmol/L during the daytime and overnight.

Conditions

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

Keywords

Type 1 diabetes; Closed-loop glucose control; Artificial Pancreas; Continuous subcutaneous insulin infusion; Continuous glucose monitoring

Outcome Measures

Primary Outcomes (1)

• The proportion of time spent in the target glucose range from 3.9 to 10.0 mmol/l based on CGM

  7 day (phase 1) and 21 day (phase 2) home study periods

Secondary Outcomes (3)

• The proportion of time spent above and below the target glucose (3.9 to 10.0 mmol/l) based on CGM.

  7 day (phase 1) and 21 day (phase 2) home study periods

• The proportion of time with glucose levels < 3.5 mmol/l and <2.8 mmol/l based on CGM

  7 day (phase 1) and 21 day (phase 2) home study periods

• The proportion of time with glucose levels in significant hyperglycaemia, as based on CGM (glucose levels > 16.7 mmol/l)

  7 day (phase 1) and 21 day (phase 2) home study periods

Other Outcomes (2)

• Safety evaluation

  7 day (phase 1) and 21 day (phase 2) home study periods

• Utility evaluation

  7 day (phase 1) and 21 day (phase 2) home study periods

Study Arms (2)

Closed-loop insulin delivery

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 day and night at home for a total duration of 7 days (phase 1) and 21 days (phase 2).

Device: Closed-loop system; Device: real-time CGM

real-time CGM alone

ACTIVE COMPARATOR

Glucose level will be controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM) during the day and night over 7 days (phase 1) and 21 days (phase 2).

Device: real-time CGM

Interventions

Closed-loop system 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.

Closed-loop insulin delivery

real-time CGM DEVICE

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

Closed-loop insulin delivery; real-time CGM alone

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• The subject is between 10 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/carer 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/carer is willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements taken every day
• HbA1c between 7.0% and 11.0 % (53 to 97mmol/mol) based on analysis from central laboratory or equivalent
• The subject is literate in English
• The subject is willing to wear closed-loop system at home and at school / college / work
• The subject is willing to follow study specific instructions

You may not qualify if:

• Non-type 1 diabetes mellitus including those secondary to chronic disease
• Any other physical or psychological disease or condition 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 have significant interference with glucose metabolism, such as systemic corticosteroids, as judged by the investigator
• Known or suspected allergy against insulin
• Subjects with clinically significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator
• Significantly reduced hypoglycaemia awareness as judged by the investigator
• Total daily insulin dose ≥ 2 IU/kg/day
• Total daily insulin dose \<10 IU/day
• Reduced hypoglycaemia awareness
• Pregnancy, planned pregnancy or breast feeding
• Severe visual impairment
• Severe hearing impairment
• Subjects using implanted internal pacemaker
• Lack of reliable telephone facility for contact

Sponsors & Collaborators

• University of Cambridge: lead
• Cambridge University Hospitals NHS Foundation Trust: collaborator

Study Sites (1)

University of Cambridge

Cambridge, CB2 0QQ, United Kingdom

Location

Related Publications (6)

• 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

• 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

• 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

• Tauschmann M, Allen JM, Wilinska ME, Thabit H, Stewart Z, Cheng P, Kollman C, Acerini CL, Dunger DB, Hovorka R. Day-and-Night Hybrid Closed-Loop Insulin Delivery in Adolescents With Type 1 Diabetes: A Free-Living, Randomized Clinical Trial. Diabetes Care. 2016 Jul;39(7):1168-74. doi: 10.2337/dc15-2078. Epub 2016 Jan 6.

  PMID: 26740634 RESULT

• Tauschmann M, Allen JM, Wilinska ME, Thabit H, Acerini CL, Dunger DB, Hovorka R. Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Suboptimally Controlled Adolescents With Type 1 Diabetes: A 3-Week, Free-Living, Randomized Crossover Trial. Diabetes Care. 2016 Nov;39(11):2019-2025. doi: 10.2337/dc16-1094. Epub 2016 Sep 9.

  PMID: 27612500 RESULT

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Roman Hovorka, PhD

  University of Cambridge

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• 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: June 5, 2013
• First Posted: June 7, 2013
• Study Start: August 28, 2014
• Primary Completion: July 31, 2015
• Study Completion: January 1, 2016
• Last Updated: March 3, 2017

Record last verified: 2017-02

Locations

GB (1)