Clinical Assessment of a Closed-loop System With Glucagon, Exercise and Mixed Meals
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Imperial College London
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Percentage of Time in Target Range Over 24 Hour
Study Overview
Brief Summary
The diabetes technology group at Imperial College have developed a bio-inspired artificial pancreas (BiAP) system which uses a control algorithm based on a mathematical model of beta-cell physiology. The algorithm is implemented on a miniature silicon microchip within a portable handheld device, which interfaces the components of the artificial pancreas.
Development of closed-loop insulin delivery devices to intensify control without hypoglycaemia has been extensively reviewed and have shown encouraging results . However, they have not yet proven to be robust when challenged with uncertainty and the external challenges (such as mixed meal contents, physical exercise, physiological stress and intercurrent illness) that people with Type 1 Diabetes Mellitus (T1DM) may be exposed to outside the clinical environment.
The principal research objective is to assess the safety and efficacy of a closed-loop system for T1DM compared to standard insulin pump therapy (open-loop). The primary outcome from the studies will be % time spent with a glucose concentration in the target range (3.9-10.0mmol/l). This outcome incorporates safety as it ensures subjects do not have low or high glucose excursions and is the principal measure of efficacy for closed-loop insulin delivery systems in the scientific literature. Other measured outcomes will be % time spent in euglycaemia (3.9-7.8mmol/l), % time spent in hypoglycaemia (<3.9mmol/l), % time spent in hyperglycaemia (>10mmol/l), mean venous blood and sensor glucose, glycaemic variability as measured by standard metrics (Standard Deviation, Continuous Overlapping Net Glycaemic Action, Lability Index, J-Index, Glycaemic Risk Assessment Diabetes Equation, Mean Of Daily Differences, Mean Amplitude of Glucose Excursion, Average Daily Risk Range, M-VALUE, Mean Average Glucose), glycaemic risk as measured by Low Blood Glucose Index (LBGI) and High Blood Glucose Index (HBGI), closed-loop error grid analysis, glucose area under the curve. All measures have been previously published and validated.
This clinical trial protocol assesses the artificial pancreas system in three separate sub-studies:
- In a bi-hormonal (insulin and glucagon) configuration
- During and after exercise with bi-hormonal closed loop, and standard insulin opened loop
- During and after meals of mixed composition with bi-hormonal closed loop, and standard insulin opened loop
Detailed Description
Methodology Randomised controlled cross-over open label study
Sub study 1 (n=10)
In sub-study 1 which includes the first bio-inspired artificial pancreas study using bi-hormonal (insulin and glucagon) control a fasting 6-hour bi-hormonal closed-loop study will be conducted to assess proof of concept and safety prior to the 25-hour randomised controlled crossover study
Each subject will then be randomised to attend either a closed-loop visit or an open-loop visit first. Once either visit is completed each subject will crossover and attend the remaining visit.
Sub-study 2 (n=20) The aim of sub-study 2 is to challenge the bi-hormonal pump during a moderate exercise. Subjects will be initially randomised to either the bi-hormonal or the standard opened loop and then cross over. Each study will last for 25 hours
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adults over 18 years of age
- •Type 1 diabetes confirmed on the basis of clinical features and a fasting c-peptide <200 pmol/L
- •Type 1 diabetes for greater than 1 year
- •Continuous subcutaneous insulin infusion for greater than 6 months
- •HbA1c < 10% (86mmol/mol)
Exclusion Criteria
- •Recurrent severe hypoglycaemia and hypoglycaemia unawareness
- •Pregnant or planning pregnancy
- •Breastfeeding
- •Enrolled in other clinical trials
- •Have active malignancy or under investigation for malignancy
- •Allergic to lactose
- •Allergic to glucagon
Arms & Interventions
Bihormonal closed loop
Bi-hormonal closed loop pump will be used in the exercise and mixed meal substudies
Intervention: Bi-hormonal closed loop pump (Device)
Standard opened loop pump
Standard opened loop pump will be used in the exercise and mixed meal substudies
Intervention: Standard opened loop pump (Device)
Insulin only
Insulin only closed loop
Intervention: Insulin closed loop (Device)
Outcomes
Primary Outcomes
Percentage of Time in Target Range Over 24 Hour
Time Frame: 24 hours
The primary outcome from the studies will be time spent with a glucose concentration in the target range (3.9-10.0mmol/l).
Secondary Outcomes
No secondary outcomes reported