Clinical trial NCT03740698: The Bio-Inspired Artificial Pancreas for the Home
Official title: The Bio-Inspired Artificial Pancreas for the Home
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2018-11-14
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a 3-way crossover open-label randomized controlled trial. Description of the three interventions for comparison are as follows:

1. Sensor augmented pump (combination of insulin pump and continuous glucose monitoring) (open-loop system)
2. Bio-inspired Artificial Pancreas (closed-loop system) with a fixed bolus calculator
3. Bio-inspired Artificial Pancreas (closed-loop system) with the Advanced Bolus Calculator for Diabetes (ABC4D)

The intervention in each arm will be assessed over 6 weeks with a minimum 2-week break in between each intervention. During the break participants will revert back to usual pump therapy.
Primary purpose: DEVICE_FEASIBILITY

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: % Time in Target Range Defined as 3.9-10mmol/l
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Clinical Research Facility
Study officials:
affiliation: Imperial College London
name: Nick Oliver
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.