Closing the Loop 24/7 in Adolescents With Type 1 Diabetes (DAN04)

February 28, 2017 updated by: Dr Roman Hovorka, University of Cambridge

An Open-label, Single-centre, Randomised, Two-period Crossover Study to Assess the Efficacy, Safety and Utility of Automated Closed-loop Glucose Control, Day and Night Over 7 Days (Phase 1) and 21 Days (Phase 2) in Comparison With Continuous Subcutaneous Insulin Infusion Combined With Continuous Glucose Monitoring in the Home Setting in Children and Adolescents T1D

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The main objective of this study is to determine the efficacy, safety and utility of automated closed-loop glucose control in the home setting over a short term period, including the daytime and during the activities of normal daily living. This study builds on previous and on-going studies of closed-loop systems that have been performed in Cambridge in children and adolescents with type 1 diabetes in the clinical research facility and in the home setting. The data and experienced gained from this study will be utilised in planning future home studies.

This is an open-label, single-centre, randomised, crossover study, involving two, 7 day (phase 1) and 21 day (phase 2) 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 in random order. A total of up to 30 children and adolescents aged 10 to 18 years with T1D on insulin pump therapy will be recruited through diabetes clinics, to allow for 12 completed subjects available for assessment in each study phase.

Subjects will receive appropriate training by the research team on the safe use of the closed-loop insulin delivery system. During the training visit in a clinical research centre, subjects will be encouraged to mimic their usual daily activities and will be allowed to walk inside hospital premises. Subjects will be advised to discontinue automated closed-loop insulin delivery and follow their usual insulin pump therapy for certain activities such as periods of strenuous exercise during the 7 day (phase 1) and 21 day (phase 2) home study phase.

The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by CGM (conservatively adjusted for potential over-estimation). Secondary outcomes are the time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises the tabulation of severe hypoglycaemic episodes.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • University of Cambridge

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Closed-loop insulin delivery
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
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.
Device: real-time CGM
Subject's glucose level is controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)
Active Comparator: real-time CGM alone
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
Subject's glucose level is controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The proportion of time spent in the target glucose range from 3.9 to 10.0 mmol/l based on CGM
Time Frame: 7 day (phase 1) and 21 day (phase 2) home study periods
7 day (phase 1) and 21 day (phase 2) home study periods

Secondary Outcome Measures

Outcome Measure
Time Frame
The proportion of time spent above and below the target glucose (3.9 to 10.0 mmol/l) based on CGM.
Time Frame: 7 day (phase 1) and 21 day (phase 2) home study periods
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
Time Frame: 7 day (phase 1) and 21 day (phase 2) home study periods
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)
Time Frame: 7 day (phase 1) and 21 day (phase 2) home study periods
7 day (phase 1) and 21 day (phase 2) home study periods

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety evaluation
Time Frame: 7 day (phase 1) and 21 day (phase 2) home study periods
Safety evaluation will comprise the number of episodes of hypoglycaemia, severe hypoglycaemia as well as nature and severity of any other adverse events, including ketone-positive hyperglycaemia.
7 day (phase 1) and 21 day (phase 2) home study periods
Utility evaluation
Time Frame: 7 day (phase 1) and 21 day (phase 2) home study periods
Utility of the system will be evaluated by the frequency and duration of use of the closed-loop system at home.
7 day (phase 1) and 21 day (phase 2) home study periods

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cambridge

Collaborators

Cambridge University Hospitals NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 28, 2014

Primary Completion (Actual)

July 31, 2015

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

June 5, 2013

First Submitted That Met QC Criteria

June 5, 2013

First Posted (Estimate)

June 7, 2013

Study Record Updates

Last Update Posted (Actual)

March 3, 2017

Last Update Submitted That Met QC Criteria

February 28, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAN04

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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