Closing the Loop in Adults With Type 1 Diabetes Under Free Living Conditions

NCT04055480 | Completed

• 1 other identifier: 136248_APHome04
• Study Type: interventional
• Target: 25
• Locations: 3 countries
• Sites: 4

Brief Summary

The main objective of this study is to determine whether home use of day and night closed loop insulin delivery under free living conditions applying faster insulin aspart (FiAsp) is non-inferior to home use of closed-loop applying standard insulin aspart. This is a double-blind, multi-centre, randomised, crossover design study, involving a run-in period followed by two study periods during which glucose levels will be controlled either by an automated closed-loop system using standard rapid acting insulin analogue or by an automated closed-loop system using faster insulin aspart in random order. Subjects will receive appropriate training in the safe use of closed-loop insulin delivery system. Subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by CGM during home stay. Secondary outcomes are the HbA1c, time spent with glucose levels above and below target, as recorded by CGM, and other CGM based metrics.

Conditions

Type 1 Diabetes

Keywords

closed-loop; artificial pancreas; insulin

Outcome Measures

Primary Outcomes (1)

• Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM).

  8 week intervention period

Secondary Outcomes (7)

• Time spent above target glucose (3.9 to 10.0 mmol/l) based on continuous subcutaneous glucose monitoring (CGM)

  8 week intervention period

• Time spent below target glucose (3.9 to 10.0 mmol/l) based on continuous subcutaneous glucose monitoring (CGM)

  8 week intervention period

• Average, standard deviation and coefficient of variation of glucose levels based on continuous subcutaneous glucose monitoring

  8 week intervention period

• The time with glucose levels < 3.5 mmol/l <3.0mmol/l and <2.8 mmol/l based on continuous subcutaneous glucose monitoring

  8 week intervention period

• The time with glucose levels in the significant hyperglycaemia, as based on continuous subcutaneous glucose monitoring (glucose levels > 16.7 mmol/l)

  8 week intervention period

Other Outcomes (2)

• Safety evaluation will comprise the number of episodes of hypoglycaemia, significant ketonemia (>3.0mmol/l) as well as nature and severity of any other adverse events.

  Through study completion, an average of 5 months

• Utility evaluation is the frequency and duration of use of the closed-loop system at home.

  8 week intervention period

Study Arms (2)

Closed-loop using standard rapid-acting insulin

ACTIVE COMPARATOR

Unsupervised home use of day and night hybrid closed loop insulin delivery system (CamAPS FX) for 8 weeks using standard rapid-acting insulin The CamAPS FX closed-loop system comprises Dana insulin pump (Diabecare, Sooil, Seoul, South Korea) Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) An Android smartphone hosting CamAPS FX Application with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump Glooko/Diasend cloud upload system to monitor CGM/insulin data.

Device: Closed-loop using standard rapid-acting insulin

Closed-loop using faster insulin aspart

EXPERIMENTAL

Unsupervised home use of day and night hybrid closed loop insulin delivery system (CamAPS FX) for 8 weeks using faster insulin aspart The CamAPS FX closed-loop system comprises Dana insulin pump (Diabecare, Sooil, Seoul, South Korea) Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) An Android smartphone hosting CamAPS FX Application with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump Glooko/Diasend cloud upload system to monitor CGM/insulin data.

Device: Closed-loop using faster insulin aspart

Interventions

Closed-loop using standard rapid-acting insulin DEVICE

Closed-loop using standard rapid-acting insulin

Closed-loop using standard rapid-acting insulin

Closed-loop using faster insulin aspart DEVICE

Closed-loop using faster insulin aspart

Closed-loop using faster insulin aspart

Eligibility Criteria

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

You may qualify if:

• The subject has type 1 diabetes as defined by WHO
• The subject is 18 years of age or older
• The subject will have been on an insulin pump for at least 6 months with good knowledge of insulin self-adjustment including carbohydrate counting
• The subject is treated with one of the rapid acting or ultra-rapid acting insulin analogues (Insulin Aspart, faster acting insulin Aspart, Insulin Lispro or Insulin Glulisine)
• HbA1c \<10% (86mmol/mol) for phase 3, based on analysis from central laboratory or equivalent
• The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 2 measurements per day
• The subject is willing to wear closed-loop system at home and at work place
• The subject is willing to follow study specific instructions including the use of bolus calculator for all meals / snacks
• The subject is willing to upload pump and CGM data at regular intervals
• Female subjects of child bearing age should be on effective contraception and must have a negative urine-HCG pregnancy test at screening.

You may not qualify if:

• Non-type 1 diabetes mellitus
• Subjects who are living alone
• Any other physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results
• Current treatment with drugs known to have significant interference with glucose metabolism, such as systemic corticosteroids, as judged by the investigator
• Known or suspected allergy against insulin or previous reaction to FiAsp
• Subjects with clinically significant nephropathy (eGFR \< 45ml/min), neuropathy or active retinopathy (defined as presence of maculopathy or more than background diabetic retinopathy changes) as judged by the investigator
• More than one episode of severe hypoglycaemia as defined by American Diabetes Association (42) in preceding 12 months (Severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions including episodes of hypoglycaemia severe enough to cause unconsciousness, seizures or attendance at hospital.)
• Total daily insulin dose \> 2 IU/kg/day
• Subject is pregnant or breast feeding or planning pregnancy within next 10 months
• Severe visual impairment
• Severe hearing impairment
• Lack of reliable telephone facility for contact
• Subject not proficient in English (UK), French (Switzerland) or German (Germany, Switzerland and Austria)
• Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
• Positive alcohol breath test.

Sponsors & Collaborators

• University of Cambridge: lead
• Manchester University NHS Foundation Trust: collaborator
• Insel Gruppe AG, University Hospital Bern: collaborator
• Medical University of Graz: collaborator

Study Sites (4)

Medical University of Graz

Graz, Austria

Location

Inselspital, Bern University Hospital

Bern, Switzerland

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust

Manchester, United Kingdom

Location

Related Publications (1)

• Haliloglu B, Boughton CK, Lakshman R, Ware J, Nwokolo M, Thabit H, Mader JK, Bally L, Leelarathna L, Wilinska ME, Allen JM, Hartnell S, Evans ML, Hovorka R. Postprandial Glucose Excursions with Ultra-Rapid Insulin Analogs in Hybrid Closed-Loop Therapy for Adults with Type 1 Diabetes. Diabetes Technol Ther. 2024 Jul;26(7):449-456. doi: 10.1089/dia.2023.0509. Epub 2024 Feb 27.

  PMID: 38315506 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Condition Hierarchy (Ancestors)

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

Study Officials

• Roman Hovorka

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Metabolic Technology

Study Record Dates

• First Submitted: August 6, 2019
• First Posted: August 13, 2019
• Study Start: August 10, 2019
• Primary Completion: June 15, 2020
• Study Completion: August 30, 2020
• Last Updated: September 2, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication.
• Access Criteria: Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication.

Locations

CH (1); AU (1); GB (2)