Closed-loop Insulin Delivery in the General Ward (ANGIE02)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2013 by University of Cambridge
Sponsor:
Collaborators:
Cambridge University Hospitals NHS Foundation Trust
European Foundation for the Study of Diabetes
Information provided by (Responsible Party):
Hood Thabit, University of Cambridge
ClinicalTrials.gov Identifier:
NCT01774565
First received: January 18, 2013
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

The main study objective is to compare conventional insulin therapy with automated closed-loop glucose control over 72 hours in achieving target glucose levels in hospitalised insulin-treated Type 2 diabetes (T2D) subjects.

This is an open-label, two-arm, randomised, parallel design study in hospitalised insulin-treated T2D subjects, during which target glucose levels will be controlled either by closed-loop system combined with real-time continuous subcutaneous glucose monitoring (CGM) or by conventional insulin therapy.


Condition Intervention Phase
Diabetes Mellitus
Device: Fully Automated Closed-Loop Insulin Delivery
Device: Conventional insulin therapy
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Single-centre, Randomised, Parallel Design Study to Assess the Efficacy and Safety of 72-hour Automated Closed-loop Glucose Control in Comparison With Conventional Treatment in Insulin Treated Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Cambridge:

Primary Outcome Measures:
  • Time spent in target glucose range (5.6-10.0mmol/l) [ Time Frame: 72-hours ] [ Designated as safety issue: Yes ]

    Primary outcome will be measured using adjusted continuous subcutaneous glucose monitoring (CGM) data.

    During the study subjects will have reference glucose (fingerstick capillary blood glucose)measured before every meal and before bedtime (4 times/day).



Secondary Outcome Measures:
  • Proportion of time with glucose levels in the target glucose range (5.6-10.0mmol/l)as recorded by reference glucose [ Time Frame: 72- hours ] [ Designated as safety issue: Yes ]

    Definition of Reference glucose = Fingerstick capillary blood glucose.

    During the study subjects will have reference glucose measured before every meal and before bedtime (4 times/day)


  • Proportion of time with glucose levels below 5.6 mmol/l and above 10.0 mmol/l as recorded by CGM and reference glucose values [ Time Frame: 72- hours ] [ Designated as safety issue: Yes ]

    Definition of Reference glucose = Fingerstick capillary blood glucose.

    During the study subjects will have reference glucose measured before every meal and before bedtime (4 times/day)


  • Proportion of time with glucose levels below 3.5 mmol/l as recorded by CGM and reference glucose values [ Time Frame: 72- hours ] [ Designated as safety issue: Yes ]

    Definition of Reference glucose = Fingerstick capillary blood glucose.

    During the study subjects will have reference glucose measured before every meal and before bedtime (4 times/day)


  • Average glucose levels, as recorded by CGM and reference glucose values [ Time Frame: 72- hours ] [ Designated as safety issue: Yes ]

    Definition of Reference glucose = Fingerstick capillary blood glucose.

    During the study subjects will have reference glucose measured every before every meal and before bedtime (4 times/day)


  • Standard deviation of glucose levels, as recorded by CGM and reference glucose [ Time Frame: 72- hours ] [ Designated as safety issue: Yes ]

    Definition of Reference glucose = Fingerstick capillary blood glucose.

    During the study subjects will have reference glucose measured before every meal and before bedtime (4 times/day)



Estimated Enrollment: 40
Study Start Date: January 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fully Automated Closed-Loop Insulin Delivery
During the fully closed-loop insulin delivery, the control algorithm will automatically direct between meals and meal-related subcutaneous insulin delivery utilizing real-time continuous glucose monitoring (RT-CGM) data. The subcutaneous insulin pump will deliver insulin Aspart (Novo Nordisk, Copenhagen, Denmark).
Device: Fully Automated Closed-Loop Insulin Delivery
Active Comparator: Conventional insulin therapy
During the conventional therapy, subject's insulin dose and regimen on admission will be adjusted as necessary by the clinical team according to Cambridge University Hospital Foundation Trust's usual clinical practise. Subjects will have masked CGM sensors inserted during the study (CGM readings will be masked throughout the study).
Device: Conventional insulin therapy

Detailed Description:

Hyperglycaemia in hospitalized patients is becoming a common clinical problem due to the increasing prevalence of diabetes mellitus . Hyperglycaemia in this cohort can also occur in patients with previously undiagnosed diabetes, or during acute illness in those with previously normal glucose tolerance. As a result, the prevalence of acute or stress hyperglycaemia in hospitalised patients has been widely reported. A growing body of evidence currently suggest that the degree of hyperglycaemia upon admission and the duration of hyperglycaemia during their illness are associated with adverse outcomes.In-patient hyperglycaemia is now widely recognised as a poor prognostic marker in terms of morbidity and mortality, increased length of stay and cost to the healthcare system.

The current management of in-patient hyperglycaemia in non-critical care is still far from ideal, and vary widely between different centres. The discordance between clinical evidence and practice is due to a number of factors which could potentially undermine patient care and safety. Of these, hypoglycaemia remains one the biggest barriers to managing in-patient hyperglycaemia. There is therefore a need to develop and validate a more effective and safer system to manage in-patient hyperglycaemia.

A closed-loop insulin infusion system has previously been tested and reported to be feasible and safe in intensive care patients. Its utilisation in non-critical patients in the general medical and surgical wards currently remains unproven. Its use in this cohort however could potentially be of significant practical and clinical value, especially in a busy ward environment. The Model Predictive Control (MPC) algorithm developed by our group at the University of Cambridge utilises fundamental glucoregulatory processes and predicts future glucose excursion resulting from projected insulin infusion rates. The algorithm can also account for the patient's meal intake and the duration of action of the short acting insulin used. This has the distinct advantage over the "reactive" approach of sliding scale insulin protocols, which treats hyperglycaemia after it has already occurred.

The MPC algorithm has been studied in intensive care and cardiac surgery patients, and results from these studies to date have been encouraging. It is shown to be associated with a significantly higher percentage of time within the blood glucose target range, without increasing the risk of severe hypoglycaemia. The expectant role of a closed-loop system using the MPC algorithm in non-critical care patients would therefore be to provide clinicians with an effective and safe method to manage hyperglycaemia in hospital.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 18 years or older
  • Type 2 Diabetes for at least 1 year as defined by WHO
  • Treatment with subcutaneous insulin alone or in combination with oral glucose-lowering medication(s)

Exclusion Criteria:

  • Autoimmune type 1 diabetes
  • Known or suspected allergy against insulin
  • Known proliferative retinopathy
  • Current or planned pregnancy or breast feeding
  • Unstable or end-stage cardiac and renal disease
  • Planned surgery during study period
  • Current in-patient in intensive care unit
  • Any physical or psychological disease or medication(s) likely to interfere with the conduct of the study and interpretation of the study results, as judged by the study clinician
  • Likely discharge earlier than 72 hours
  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: NCT01774565

Contacts
Contact: Hood Thabit, MBBCh, MRCP, MD ht312@medschl.cam.ac.uk

Locations
United Kingdom
Cambridge University Hospitals NHS Foundation Trust Not yet recruiting
Cambridge, United Kingdom
Contact: Hood Thabit, MB BCh MRCP MD       ht312@medschl.cam.ac.uk   
Principal Investigator: Anthony Coll, MBBS PhD         
Principal Investigator: Mark Evans, MBBS, MD, FRCP         
Principal Investigator: David Simmons, MBBS, MD, FRCP         
Principal Investigator: Roman Hovorka, PhD, MSc, BSc         
Sponsors and Collaborators
University of Cambridge
Cambridge University Hospitals NHS Foundation Trust
European Foundation for the Study of Diabetes
Investigators
Principal Investigator: Roman Hovorka, PhD, MSc, BSc University of Cambridge
  More Information

No publications provided

Responsible Party: Hood Thabit, Clinical Investigator, University of Cambridge
ClinicalTrials.gov Identifier: NCT01774565     History of Changes
Other Study ID Numbers: ANGIE02, A092763
Study First Received: January 18, 2013
Last Updated: November 13, 2013
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Cambridge:
Diabetes
Insulin
Closed-Loop
Real-time CGM
Subcutaneous insulin pump
Hospital

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014