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

NCT02397265 | Completed Results DMC

• 1 other identifier: 14SM2107
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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:

1. 1.In a bi-hormonal (insulin and glucagon) configuration
2. 2.During and after exercise with bi-hormonal closed loop, and standard insulin opened loop
3. 3.During and after meals of mixed composition with bi-hormonal closed loop, and standard insulin opened loop

Conditions

Type 1 Diabetes

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Time in Target Range Over 24 Hour

  The primary outcome from the studies will be time spent with a glucose concentration in the target range (3.9-10.0mmol/l).

  24 hours

Study Arms (3)

Bihormonal closed loop

EXPERIMENTAL

Bi-hormonal closed loop pump will be used in the exercise and mixed meal substudies

Device: Bi-hormonal closed loop pump

Standard opened loop pump

ACTIVE COMPARATOR

Standard opened loop pump will be used in the exercise and mixed meal substudies

Device: Standard opened loop pump

Insulin only

PLACEBO COMPARATOR

Insulin only closed loop

Device: Insulin closed loop

Interventions

Bi-hormonal closed loop pump DEVICE

Using a bio-inspired artificial pancreas consisting of a bi-hormonal closed loop pump

Bihormonal closed loop

Standard opened loop pump DEVICE

Using a standard opened loop pump

Standard opened loop pump

Insulin closed loop DEVICE

Using a closed loop

Insulin only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College

London, United Kingdom

Location

Related Publications (9)

• Nathan D, Cleary P, Backlund J, Genuth S, Lachin J, Orchard T, Raskin R, 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,

  BACKGROUND

• 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.

  PMID: 18694975 BACKGROUND

• Sovik O, Thordarson H. Dead-in-bed syndrome in young diabetic patients. Diabetes Care. 1999 Mar;22 Suppl 2:B40-2.

  PMID: 10097898 BACKGROUND

• 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.

  PMID: 21343892 BACKGROUND

• Cobelli C, Renard E, Kovatchev B. Artificial pancreas: past, present, future. Diabetes. 2011 Nov;60(11):2672-82. doi: 10.2337/db11-0654. No abstract available.

  PMID: 22025773 BACKGROUND

• 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. doi: 10.1177/193229681000400604.

  PMID: 21129325 BACKGROUND

• 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.

  PMID: 20144397 BACKGROUND

• 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.

  PMID: 22768892 BACKGROUND

• 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. doi: 10.1177/193229681300700416.

  PMID: 23911175 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Motor Activity

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Behavior

Results Point of Contact

• Title: Nick Oliver
• Organization: Imperial College London

nick.oliver@imperial.ac.uk

020 7594 2460

Study Officials

• Nick Oliver, MRCP

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: March 24, 2015
• Study Start: December 3, 2014
• Primary Completion: July 22, 2015
• Study Completion: July 22, 2015
• Last Updated: November 1, 2019
• Results First Posted: November 1, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)