The Bio-Inspired Artificial Pancreas for the Home (BiAP@home)

The purpose of the study is to evaluate the safety and effectiveness of a closed-loop insulin delivery system (also known as an artificial pancreas) which is made up of three components that communicate with each other:

1. A glucose sensor that measures glucose every 5 minutes
2. A control algorithm that calculates the required insulin dose
3. An insulin pump that delivers the insulin calculated

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Device: BiAP; Device: ABC4D

Detailed Description

In addition to assessing the closed-loop insulin delivery system on its own, the study aims to evaluate the system when combined with a personalised bolus calculator that adapts over time. Standard bolus calculators are widely used in type 1 diabetes self-management to calculate insulin boluses at mealtimes and are incorporated in all insulin pumps and in some glucose meters. A standard bolus calculator uses a generic formula taking into account the target glucose level, current glucose level, carbohydrate content of meal (grams), insulin: carbohydrate ratio (the amount of carbohydrate (grams) covered by 1 unit of insulin), insulin sensitivity factor (the reduction in blood glucose by 1 unit of insulin) and insulin-on-board (IOB, the remaining active insulin from the previous bolus). Some bolus calculators additionally consider parameters such as exercise, but all lack the ability to automatically adapt over time to respond to individual needs.

Finally, the study aims to compare the closed-loop insulin delivery system to standard pump therapy (also known as an open-loop insulin delivery system) in combination with continuous glucose monitoring (referred to as sensor augmented pump).

The Diabetes Technology group at Imperial College have developed a unique closed-loop insulin delivery system known as the Bio-inspired Artificial Pancreas (BiAP) and a personalised bolus calculator known as the Advanced Bolus Calculator for Diabetes (ABC4D).

Overview of the complete closed-loop system (artificial pancreas) used in this study is as follows:

1. A commercially available continuous subcutaneous glucose sensor (Dexcom G5 CGM system).
2. The BiAP control algorithm implemented in a low-power handheld device (developed at Imperial College)

3. An insulin infusion pump (Tandem t:slim) for insulin delivery.

   In one part of the study the closed-loop system will be evaluated in combination with:

4. The ABC4D adaptive bolus calculator implemented in a smartphone (as an app)

All the components will be tested together as a combined system.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Imperial College Clinical Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults over 18 years of age
• Type 1 diabetes confirmed on the basis of clinical features and a random c-peptide <200 pmol/L
• Type 1 diabetes for greater than 1 year
• Continuous subcutaneous insulin infusion for greater than 6 months
• Structured education done (either 1:1 or group education)
• HbA1c <10% (86mmol/mol)
• A negative pregnancy test in female participants of childbearing age

Exclusion Criteria:

• More than one episode of severe hypoglycaemia (defined as hypoglycaemia requiring 3rd party assistance) in the preceding year
• Impaired awareness of hypoglycaemia (Gold score >4)
• Pregnant or planning pregnancy
• Breastfeeding
• Enrolled in other clinical trials
• Have active malignancy or under investigation for malignancy
• Severe visual impairment
• Reduced manual dexterity
• Ischaemic heart disease
• Anti-anginal medications
• Regular use of paracetamol
• Unable to participate due to other factors, as assessed by the Chief Investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: SAP, open-loop; Sensor augmented pump (combination of insulin pump and continuous glucose monitoring) (open-loop system)
Experimental: BiAP, fixed bolus calculator; Bio-inspired Artificial Pancreas (closed-loop system) with a fixed bolus calculator	Device: BiAP; The bio-inspired artificial pancreas (BiAP) system uses a control algorithm based on a mathematical model of beta-cell behaviour derived from physiological experiments, carried out by other groups, which have demonstrated how the beta cells in the pancreas produce insulin in people without diabetes. Utilising the data from these experiments it has been possible to implement the behaviour of the beta cell in software and we have used a simulator with 200 virtual patients to demonstrate the safety and efficacy of the algorithm. The data from the simulator have previously been published. The BiAP algorithm is implemented on a miniature silicon microchip within a portable handheld device, which interfaces the components of the artificial pancreas.
Experimental: BiAP, ABC4D; Bio-inspired Artificial Pancreas (closed-loop system) with the Advanced Bolus Calculator for Diabetes (ABC4D)	Device: BiAP; The bio-inspired artificial pancreas (BiAP) system uses a control algorithm based on a mathematical model of beta-cell behaviour derived from physiological experiments, carried out by other groups, which have demonstrated how the beta cells in the pancreas produce insulin in people without diabetes. Utilising the data from these experiments it has been possible to implement the behaviour of the beta cell in software and we have used a simulator with 200 virtual patients to demonstrate the safety and efficacy of the algorithm. The data from the simulator have previously been published. The BiAP algorithm is implemented on a miniature silicon microchip within a portable handheld device, which interfaces the components of the artificial pancreas.; Device: ABC4D; The Advanced Bolus Calculator for Diabetes (ABC4D) is a novel, adaptive decision support algorithm based on case-based reasoning (CBR) providing real-time insulin advice through a smartphone application.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% Time in Target Range Defined as 3.9-10mmol/l	Interstitial blood glucose will be measured every 5 minutes via CGM for a period of six months (original plan) The study was terminated early. Only two participants entered the allocated study arm and remained in the study for two weeks.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% time spent in euglycaemia (3.9-7.8mmol/l)	Interstitial blood glucose will be measured every 5 minutes via CGM for a period of six months	6 months
% time spent in hypoglycaemia (<3.9mmol/l)	Interstitial blood glucose will be measured every 5 minutes via CGM for a period of six months	6 months
% time spent in hypoglycaemia (<2.8mmol/l)	Interstitial blood glucose will be measured every 5 minutes via CGM for a period of six months	6 months
% time spent in hyperglycaemia (>10mmol/l)	Interstitial blood glucose will be measured every 5 minutes via CGM for a period of six months	6 months
% time spent in severe hyperglycaemia (<15mmol/l)	Interstitial blood glucose will be measured every 5 minutes via CGM for a period of six months	6 months
Mean sensor glucose	Interstitial blood glucose will be measured every 5 minutes via CGM for a period of six months	6 months
Glycaemic variability	Calculation using CGM data	6 months
Glycaemic risk as measured by LBGI and HBG	Calculation using CGM data	6 months
Closed loop error grid analysis	Calculation using CGM data	6 months
Glucose area under the curve	Calculation using CGM data	6 months
Insulin requirement in units/kg/hr	Calculation using average insulin delivered per hour and bodyweight	6 months
Hypoglycaemia awareness (Gold scores)	Quantitative Gold score questionnaire	6 months
Quality of life Questionnaire	Measured via validated questionnaire	6 months
Cost-effectiveness	Cost of equipment when compared with standard of care	6 months
Device usability	Measured via validated questionnaire	6 months
% time in closed loop control	Calculation using BiAP data	6 months
Severe hypoglycaemia	Calculation using CGM data	6 months
Diabetic ketoacidosis	Incidences of DKA	6 months
Sensor MAD%	Calculation using CGM data	6 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Nick Oliver, Imperial College London

Publications and helpful links

General Publications

• Herrero P, Pesl P, Reddy M, Oliver N, Georgiou P, Toumazou C. Advanced Insulin Bolus Advisor Based on Run-To-Run Control and Case-Based Reasoning. IEEE J Biomed Health Inform. 2015 May;19(3):1087-96. doi: 10.1109/JBHI.2014.2331896.
• Kovatchev BP, Breton M, Man CD, Cobelli C. In silico preclinical trials: a proof of concept in closed-loop control of type 1 diabetes. J Diabetes Sci Technol. 2009 Jan;3(1):44-55. doi: 10.1177/193229680900300106.
• Oliver N, Georgiou P, Johnston D, Toumazou C. A benchtop closed-loop system controlled by a bio-inspired silicon implementation of the pancreatic beta cell. J Diabetes Sci Technol. 2009 Nov 1;3(6):1419-24. doi: 10.1177/193229680900300623.
• Herrero P, Georgiou P, Oliver N, Johnston DG, Toumazou C. A bio-inspired glucose controller based on pancreatic beta-cell physiology. J Diabetes Sci Technol. 2012 May 1;6(3):606-16. doi: 10.1177/193229681200600316.
• Georgiou P, Toumazou C. A silicon pancreatic Beta cell for diabetes. IEEE Trans Biomed Circuits Syst. 2007 Mar;1(1):39-49. doi: 10.1109/TBCAS.2007.893178.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): January 31, 2022
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: November 7, 2018
• First Submitted That Met QC Criteria: November 13, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): February 5, 2024
• Last Update Submitted That Met QC Criteria: May 25, 2023
• Last Verified: May 1, 2023

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
• Other Study ID Numbers: 17HH3730

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No