Closing the Loop in Adults With Type 1 Diabetes - Alcohol Consumption (ANGELA02)

Randomised, Two-Period Crossover Study to Assess the Efficacy of Overnight Computer-based Glucose Control Compared With Conventional Pump Therapy Following the Consumption of Alcohol in Adults With Type 1 Diabetes

The main objective is to assess the efficacy and safety of overnight automated closed loop glucose control using a computer-based algorithm compared with conventional insulin pump therapy in adults with type 1 diabetes following the consumption of a moderate amount of alcohol at dinnertime.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: Closed loop; Device: Conventional insulin pump delivery

Detailed Description

People with type 1 diabetes need regular insulin injections or continuous delivery of insulin using an insulin pump. Keeping blood sugars in the normal range is known to reduce the risk of long term 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 of the person developing episodes of low glucose levels (hypoglycaemia). One solution is using 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. This system is being developed in Cambridge and is undergoing trials in children and adults with type 1 diabetes. Results thus far show that the system is very effective at preventing hypoglycaemia and maintaining blood glucose levels in target range.

We plan to test the closed loop in various challenging conditions faced by patients in daily life. One of these is the consumption of alcohol, which can give rise to delayed hypoglycaemia in patients with diabetes. The studies will be done in a clinical research facility under supervised conditions. Subjects will attend for two study nights where they will receive a specific volume of alcohol with an evening meal. On one night this will be followed by closed loop algorithm control of their insulin overnight. On the other (control) night subjects will remain on their usual pump therapy regime overnight.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 1 diabetes, as defined by WHO for at least 6 months or confirmed C-peptide negative
• On insulin pump therapy for at least 3 months

Exclusion Criteria:

• Non-type 1 diabetes mellitus
• Any physical/psychological disease likely to interfere with the study
• Taking medication likely to interfere with interpretation of results
• Known/suspected allergy against insulin
• Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator
• Unstable blood glucose control, including recurrent severe hypoglycaemia as judged by the investigator
• Current pregnancy/breastfeeding
• Total daily insulin dose > 1.4 IU/kg
• HbA1C > 10% within the last 3 months
• Unable/unwilling to consume the necessary quantity of alcohol stated in the study protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Closed loop (algorithm); Subcutaneous delivery of Novorapid insulin, dose calculated by computer-driven control algorithm, based on continuous glucose sensor readings	Device: Closed loop; Subcutaneous delivery of Novorapid insulin, dose calculated by control algorithm, based on continuous glucose sensor readings
Placebo Comparator: Open loop; Subcutaneous delivery of Novorapid insulin according to usual pump regime	Device: Conventional insulin pump delivery; Subcutaneous delivery of Novorapid insulin according to usual pump regime

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of plasma glucose values in target (3.9-8.0 mmol/L)	2200-1200hr

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of CGM (continuous glucose monitoring) values in target (3.9-8.0 mmol/L)	2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs
Percentage of plasma glucose and CGM values in target (3.9-8.0 mmol/L)	0000-0400; 0400-0800; 0800-1200; 0300-1200hrs
Percentage of plasma glucose and CGM values below 3.9 mmol/L	2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs
Percentage of plasma glucose and CGM values above 8.0 mmol/L	2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs
Average plasma and CGM glucose	2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs
Average plasma insulin concentration	2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs
Total dose of insulin administered	2200-1200hrs
Low blood glucose index (LBGI) score	2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs
High blood glucose index (HBGI) score	2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs
Percentage of plasma glucose and CGM values below 3.0 mmol/L	2200-1200; 0000-0400; 0400-0800; 0800-1200; 0300-1200hrs

Collaborators and Investigators

• Sponsor: University of Cambridge
• Collaborators: Cambridge University Hospitals NHS Foundation Trust
• Investigators: Principal Investigator: Mark L Evans, MD FRCP, University of Cambridge, UK; Study Director: Roman Hovorka, PhD, University of Cambridge, UK

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: July 21, 2009
• First Submitted That Met QC Criteria: July 21, 2009
• First Posted (Estimate): July 23, 2009

Study Record Updates

• Last Update Posted (Estimate): May 12, 2010
• Last Update Submitted That Met QC Criteria: May 10, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 09/H0306/44