Clinical Assessment of a Closed-loop System With Glucagon, Exercise and Mixed Meals

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ClinicalTrials.gov Identifier: NCT02397265

Recruitment Status : Completed

First Posted : March 24, 2015

Results First Posted : November 1, 2019

Last Update Posted : November 1, 2019

Sponsor:

Information provided by (Responsible Party):

Imperial College London

Study Description

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

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Device: Bi-hormonal closed loop pump Device: Standard opened loop pump Device: Insulin closed loop	Not Applicable

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	24 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Clinical Assessment of a Closed-loop System With Glucagon, Exercise and Mixed Meals
Actual Study Start Date :	December 3, 2014
Actual Primary Completion Date :	July 22, 2015
Actual Study Completion Date :	July 22, 2015

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Type 1 diabetes

MedlinePlus related topics: Exercise and Physical Fitness

Drug Information available for: Insulin Glucagon

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bihormonal closed loop Bi-hormonal closed loop pump will be used in the exercise and mixed meal substudies	Device: Bi-hormonal closed loop pump Using a bio-inspired artificial pancreas consisting of a bi-hormonal closed loop pump
Active Comparator: Standard opened loop pump Standard opened loop pump will be used in the exercise and mixed meal substudies	Device: Standard opened loop pump Using a standard opened loop pump
Placebo Comparator: Insulin only Insulin only closed loop	Device: Insulin closed loop Using a closed loop

Outcome Measures

Primary Outcome Measures :

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).

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02397265

Locations

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United Kingdom
Imperial College
London, United Kingdom

Sponsors and Collaborators

Imperial College London

Investigators

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Principal Investigator:	Nick Oliver, MRCP	Imperial College London

More Information

Publications:

Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005 Dec 22;353(25):2643-53.

Buckingham B, Wilson DM, Lecher T, Hanas R, Kaiserman K, Cameron F. Duration of nocturnal hypoglycemia before seizures. Diabetes Care. 2008 Nov;31(11):2110-2. doi: 10.2337/dc08-0863. Epub 2008 Aug 11.

Sovik O, Thordarson H. Dead-in-bed syndrome in young diabetic patients. Diabetes Care. 1999 Mar;22 Suppl 2:B40-2. Erratum in: Diabetes Care 1999 Aug;22(8):1389.

Hovorka R. Closed-loop insulin delivery: from bench to clinical practice. Nat Rev Endocrinol. 2011 Feb 22;7(7):385-95. doi: 10.1038/nrendo.2011.32. Review.

Cobelli C, Renard E, Kovatchev B. Artificial pancreas: past, present, future. Diabetes. 2011 Nov;60(11):2672-82. doi: 10.2337/db11-0654. Review.

Ward WK, Massoud RG, Szybala CJ, Engle JM, El Youssef J, Carroll JM, Roberts CT Jr, DiMarchi RD. In vitro and in vivo evaluation of native glucagon and glucagon analog (MAR-D28) during aging: lack of cytotoxicity and preservation of hyperglycemic effect. J Diabetes Sci Technol. 2010 Nov 1;4(6):1311-21.

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.

Herrero P, Georgiou P, Oliver N, Johnston DG, Toumazou C. A bio-inspired glucose controller based on pancreatic β-cell physiology. J Diabetes Sci Technol. 2012 May 1;6(3):606-16.

Herrero P, Georgiou P, Oliver N, Reddy M, Johnston D, Toumazou C. A composite model of glucagon-glucose dynamics for in silico testing of bihormonal glucose controllers. J Diabetes Sci Technol. 2013 Jul 1;7(4):941-51.

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Responsible Party:	Imperial College London
ClinicalTrials.gov Identifier:	NCT02397265 History of Changes
Other Study ID Numbers:	14SM2107
First Posted:	March 24, 2015 Key Record Dates
Results First Posted:	November 1, 2019
Last Update Posted:	November 1, 2019
Last Verified:	October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Imperial College London:


Type 1 diabetes Hypoglycaemia Closed loop insulin pump Artificial pancreas	Exercise Mixed meals Bihormonal pump

Additional relevant MeSH terms:

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Diabetes Mellitus, Type 1 Diabetes Mellitus Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Autoimmune Diseases Immune System Diseases Insulin	Insulin, Globin Zinc Glucagon Hypoglycemic Agents Physiological Effects of Drugs Gastrointestinal Agents Hormones Hormones, Hormone Substitutes, and Hormone Antagonists

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