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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Cambridge
Sponsor:
Collaborator:
Cambridge University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
Dr Roman Hovorka, University of Cambridge
ClinicalTrials.gov Identifier:
NCT01873066
First received: June 5, 2013
Last updated: July 15, 2014
Last verified: July 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 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 in adolescents with type 1 diabetes. In the present study we are planning to study 12 young people aged 10-18 years on insulin pump therapy. This study will involve two 7 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.


Condition Intervention
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Endocrine System Diseases
Autoimmune Diseases
Device: Closed-loop system
Device: real-time CGM

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, Single-centre, Randomised, Two-period Crossover Study to Assess the Efficacy, Safety and Utility of Closed-loop Day and Night Over 7 Days, in Comparison With CGM in the Home Setting in Children and Adolescents With T1D

Resource links provided by NLM:


Further study details as provided by University of Cambridge:

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

Secondary Outcome Measures:
  • 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 home study periods ] [ Designated as safety issue: Yes ]
  • The proportion of time with glucose levels < 3.5 mmol/l and <2.8 mmol/l based on CGM [ Time Frame: 7 day home study periods ] [ Designated as safety issue: Yes ]
  • The proportion of time with glucose levels in significant hyperglycaemia, as based on CGM (glucose levels > 16.7 mmol/l) [ Time Frame: 7 day home study periods ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Safety evaluation [ Time Frame: 7 day home study periods ] [ Designated as safety issue: Yes ]
    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.

  • Utility evaluation [ Time Frame: 7 day home study periods ] [ Designated as safety issue: No ]
    Utility of the system will be evaluated by the frequency and duration of use of the closed-loop system at home.


Estimated Enrollment: 12
Study Start Date: July 2014
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Device: real-time CGM
Subject's glucose level is controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)

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 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 18 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.

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 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.

  Eligibility

Ages Eligible for Study:   10 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 7.5% and 10.0 % (58 to 86mmol/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
  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: NCT01873066

Contacts
Contact: Roman Hovorka, PhD +44 (0)1223 762 862 rh347@cam.ac.uk

Locations
United Kingdom
University of Cambridge Recruiting
Cambridge, United Kingdom, CB2 0QQ
Principal Investigator: David Dunger, MD, FRCPCH         
Principal Investigator: Carlo Acerini, MD, FRCPCH         
Sponsors and Collaborators
University of Cambridge
Cambridge University Hospitals NHS Foundation Trust
Investigators
Study Director: Roman Hovorka, PhD University of Cambridge
  More Information

Publications:
Responsible Party: Dr Roman Hovorka, Director of Research, University of Cambridge
ClinicalTrials.gov Identifier: NCT01873066     History of Changes
Other Study ID Numbers: DAN04
Study First Received: June 5, 2013
Last Updated: July 15, 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
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014