NCT01774565

Brief Summary

The study assesses the efficacy and safety of closed-loop glucose control in patients with insulin-treated type 2 diabetes. Phase 1 The study objective is to compare conventional insulin therapy with closed-loop glucose control combined with once daily basal insulin injection over 72 hours in hospitalised insulin treated T2D subjects. Phase 2 The study objective is to compare conventional insulin therapy with closed-loop glucose control up to maximum 15 days in hospitalised insulin treated T2D subjects. Phase 3 The study objective is to compare conventional insulin therapy with closed-loop glucose control applying faster insulin aspart up to maximum 15 days in insulin-treated inpatients receiving parenteral and/or enteral nutrition. Phase 4 The study objective is to compare automated closed-loop control using faster acting insulin aspart with closed-loop control using standard insulin aspart.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
43

participants targeted

Target at P25-P50 for not_applicable diabetes-mellitus

Timeline
Completed

Started Aug 2016

Typical duration for not_applicable diabetes-mellitus

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 18, 2013

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 24, 2013

Completed
3.5 years until next milestone

Study Start

First participant enrolled

August 1, 2016

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 21, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 21, 2018

Completed
Last Updated

October 19, 2018

Status Verified

October 1, 2018

Enrollment Period

2.1 years

First QC Date

January 18, 2013

Last Update Submit

October 18, 2018

Conditions

Diabetes Mellitus

Keywords

DiabetesInsulinClosed-LoopReal-time CGMSubcutaneous insulin pumpHospital

Outcome Measures

Primary Outcomes (1)

  • Time spent in target glucose range (5.6-10.0mmol/l)

    Primary outcome will be measured using continuous subcutaneous glucose monitoring (CGM) data (Phase 1-3) and plasma (Phase 4).

    Phase 1 (Pilot study) = 72-hours, Phase 2 (Follow-up study) = Up to 15 days

Secondary Outcomes (13)

  • Proportion of time with glucose levels below 5.6 mmol/l and above 10.0 mmol/l as recorded by CGM

    Phase 1 (Pilot study) = 72-hours, Phase 2 and Phase 3 (Follow-up study)= Up to 15 days, Phase 4=between 07:00 and 17:00

  • Average glucose levels, as recorded by CGM

    Phase 1 (Pilot study) = 72-hours, Phase 2 and Phase 3 (Follow-up study)= Up to 15 days, Phase 4=between 07:00 and 17:00

  • Proportion of time with glucose levels below 3.9 mmol/l as recorded by CGM

    Phase 1 (Pilot study) = 72-hours, Phase 2 and Phase 3 (Follow-up study)= Up to 15 days, Phase 4=between 07:00 and 17:00

  • Proportion of time with glucose levels below 3.0 mmol/l as recorded by CGM

    Phase 2 and Phase 3 (Follow-up study)= Up to 15 days, Phase 4= over 10 hours

  • Proportion of time with glucose levels below 2.8 mmol/l as recorded by CGM

    Phase 2 and Phase 3 (Follow-up study)= Up to 15 days, Phase 4= over 10 hours

  • +8 more secondary outcomes

Other Outcomes (21)

  • Overnight period: Proportion of time with Glucose levels in target range (5.6-10.0mmol/l) as recorded by CGM

    Phase 2-3 (Follow-up study) = Up to 15 days

  • Overnight period: Average glucose levels, as recorded by CGM

    Phase 2-3 (Follow-up study) = Up to 15 days

  • Overnight period: Standard deviation and coefficient of variation of glucose levels, as recorded by CGM

    Phase 2-3 (Follow-up study) = Up to 15 days

  • +18 more other outcomes

Study Arms (2)

Fully Automated Closed-Loop Insulin Delivery (phase 1-4)

EXPERIMENTAL

The control algorithm will automatically direct between meals and meal-related subcutaneous insulin delivery utilizing real-time continuous glucose monitoring (RT-CGM) data. The subcutaneous insulin pump will deliver insulin Aspart or similar. In phase 1, a once daily basal insulin analogue will also be given subcutaneously at 20% the patient's usual total daily dose. In phase 3 and 4 faster-acting insulin aspart (Fiasp) is applied.

Device: Fully Automated Closed-Loop Insulin Delivery

Usual care/ fully-automated closed-loop using Iasp

ACTIVE COMPARATOR

Phase 1-3: During usual care (conventional therapy), subject's s.c. insulin dose and regimen on admission will be adjusted as necessary by the clinical team according to local centres' usual clinical practice. Subjects will have masked CGM sensors inserted during the study (CGM readings will be masked throughout the study). Phase 4: subjects will receive fully-automated insulin delivery using standard insulin aspart (Iasp)

Device: Conventional insulin therapy

Interventions

Fully Automated Closed-Loop Insulin DeliveryDEVICE
Fully Automated Closed-Loop Insulin Delivery (phase 1-4)
Conventional insulin therapyDEVICE
Usual care/ fully-automated closed-loop using Iasp

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Aged 18 years or older
  • Type 2 Diabetes for at least 1 year as defined by WHO (phase 1 and 4)
  • Inpatient hyperglycaemia requiring subcutaneous insulin therapy (phase 2 and 3)
  • Treatment with subcutaneous insulin alone or in combination with oral glucose-lowering medication(s) (phase 4: basal bolus insulin regime for at least 3 months)
  • Receiving parenteral and/or enteral nutrition (phase 3)
  • HbA1c\<11.0% (phase 4)

You may not qualify if:

  • Autoimmune type 1 diabetes
  • Known or suspected allergy against insulin
  • Known proliferative retinopathy
  • Current or planned pregnancy or breast feeding
  • Unstable or end-stage cardiac and renal disease (phase 1 only)
  • Planned surgery during study period (phase 1 only)
  • Current in-patient in intensive care unit
  • Any physical or psychological disease or medication(s) likely to interfere with the conduct of the study and interpretation of the study results, as judged by the study clinician
  • Likely discharge earlier than 72 hours (phase 1 only)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Inselspital, Bern University Hospital, University of Bern, Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism

Bern, 3010, Switzerland

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, United Kingdom

Location

Related Publications (4)

  • Bally L, Gubler P, Thabit H, Hartnell S, Ruan Y, Wilinska ME, Evans ML, Semmo M, Vogt B, Coll AP, Stettler C, Hovorka R. Fully closed-loop insulin delivery improves glucose control of inpatients with type 2 diabetes receiving hemodialysis. Kidney Int. 2019 Sep;96(3):593-596. doi: 10.1016/j.kint.2019.03.006. Epub 2019 Mar 20.

    PMID: 31133457DERIVED

  • Boughton CK, Bally L, Martignoni F, Hartnell S, Herzig D, Vogt A, Wertli MM, Wilinska ME, Evans ML, Coll AP, Stettler C, Hovorka R. Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 2019 May;7(5):368-377. doi: 10.1016/S2213-8587(19)30061-0. Epub 2019 Mar 29.

    PMID: 30935872DERIVED

  • Bally L, Thabit H, Hartnell S, Andereggen E, Ruan Y, Wilinska ME, Evans ML, Wertli MM, Coll AP, Stettler C, Hovorka R. Closed-Loop Insulin Delivery for Glycemic Control in Noncritical Care. N Engl J Med. 2018 Aug 9;379(6):547-556. doi: 10.1056/NEJMoa1805233. Epub 2018 Jun 25.

    PMID: 29940126DERIVED

  • Thabit H, Hartnell S, Allen JM, Lake A, Wilinska ME, Ruan Y, Evans ML, Coll AP, Hovorka R. Closed-loop insulin delivery in inpatients with type 2 diabetes: a randomised, parallel-group trial. Lancet Diabetes Endocrinol. 2017 Feb;5(2):117-124. doi: 10.1016/S2213-8587(16)30280-7. Epub 2016 Nov 9.

    PMID: 27836235DERIVED

MeSH Terms

Conditions

Diabetes MellitusInsulin Resistance

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesHyperinsulinism

Study Officials

  • Roman Hovorka, PhD, MSc, BSc

    University of Cambridge

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Randomised parallel (phase 1-3) and randomised crossover (phase 4)
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Clinical Investigator

Study Record Dates

First Submitted

January 18, 2013

First Posted

January 24, 2013

Study Start

August 1, 2016

Primary Completion

September 21, 2018

Study Completion

September 21, 2018

Last Updated

October 19, 2018

Record last verified: 2018-10

Locations

GB(1)CH(1)