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Closing the Loop in Adults With Type 1 Diabetes and HbA1C<7.5% Under Free Living Conditions

Primary Purpose

Type 1 Diabetes

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Florence D2A or similar closed loop glucose control system
CSII with CGM
Sponsored by
University of Cambridge
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring closed loop glucose control, hypoglycemia, type 1 diabetes, HbA1C<7.5%

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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 insulin analogues (Insulin Aspart, Insulin Lispro or Insulin Glulisine)
  • HbA1c <7.5% (58mmol/mmol) based on analysis from central laboratory or equivalent
  • The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 6 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
  • 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.

Exclusion Criteria:

  • Non-type 1 diabetes mellitus
  • 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
  • Subjects with clinically significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator
  • Significantly reduced hypoglycaemia awareness as judged by the investigator
  • More than one episode of severe hypoglycaemia as defined by American Diabetes Association in preceding 6 months (Severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions).
  • Random C-peptide > 100pmol/l with concomitant plasma glucose >4 mM(72 mg/dl) Total daily insulin dose > 2 IU/kg/day
  • Subject is pregnant or breast feeding or planning pregnancy in near future (within next 3 months)
  • Severe visual impairment
  • Severe hearing impairment
  • Subjects using implanted internal pacemaker
  • Lack of reliable telephone facility for contact
  • Subject not proficient in English (UK) or German (Austria)
  • Subjects who are living alone
  • Additional exclusion criteria specific for Austria: Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
  • Additional exclusion criteria specific for Austria:Positive alcohol breath test.

Sites / Locations

  • Medical University of Graz
  • Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

day and night closed loop control

usual insulin pump therapy management

Arm Description

Subjects glucose levels are controlled by Florence D2A or similar closed loop insulin delivery system

Subject glucose level controlled by usual insulin pump therapy in conjunction with continuous glucose monitoring (FreeStyle Navigator CGM)

Outcomes

Primary Outcome Measures

Time spent in the target glucose range (3.9 to 10.0 mmol/l) based on subcutaneous glucose monitoring
Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) during the 4 weeks of home stay. Intention to treat basis.

Secondary Outcome Measures

Continuous subcutaneous glucose monitoring (CGM) based outcome
Time spent above and below the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) during the 4 weeks of home stay. Intention to treat basis.
Continuous subcutaneous glucose monitoring (CGM) based outcome
Average,standard deviation and coefficient of variation of glucose levels during 4 weeks of home periods
Continuous subcutaneous glucose monitoring (CGM) based outcome
The time with glucose levels < 3.5 mmol/l and <2.8 mmol/l during 4 weeks of home periods
Continuous subcutaneous glucose monitoring (CGM) based outcome
The time with glucose levels in the significant hyperglycaemia,(glucose levels > 16.7 mmol/l during 4 weeks of home periods
Continuous subcutaneous glucose monitoring (CGM) based outcome
Low Blood Glucose Index
Continuous subcutaneous glucose monitoring (CGM) based outcome
The "Area Under the Curve" below 3.5 mmol/l during 4 weeks home periods
Continuous subcutaneous glucose monitoring (CGM) based outcome
Between 24 hour period variability: Coefficient of variation of CGM glucose between 24 hour periods (midnight to midnight)
Continuous subcutaneous glucose monitoring (CGM) based outcome during overnight period between 24:00 and 06:00
Time spent with CGM glucose concentration in range 3.9-10.0mmol/L
Continuous subcutaneous glucose monitoring (CGM) based outcome during day period between 06:00 to 24:00
Time spent with CGM glucose concentration in the target range (3.9-10.0mmol/L)
Insulin dose
Total, basal and bolus insulin dose during 4 weeks of home periods
Adverse Events
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
Utility Evaluation
Utility evaluation is the percentage of closed-loop operation time during use at home, and when CGM was available

Full Information

First Posted
March 29, 2016
Last Updated
October 9, 2016
Sponsor
University of Cambridge
Collaborators
Medical University of Graz
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1. Study Identification

Unique Protocol Identification Number
NCT02727231
Brief Title
Closing the Loop in Adults With Type 1 Diabetes and HbA1C<7.5% Under Free Living Conditions
Official Title
Closing the Loop in Adults With Type 1 Diabetes and HbA1C<7.5% Under Free Living Conditions
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
March 2016 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cambridge
Collaborators
Medical University of Graz

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The main objective of this study is to determine whether day and night closed-loop insulin delivery for 4 weeks under free living conditions is superior to usual insulin pump therapy in adults with type 1 diabetes and HbA1C<7.5%. This is an open-label, multi center, randomized, crossover design study, involving a 2-4 week run-in period, followed by two 4 weeks study periods during which glucose levels will be controlled either by an automated day- and night closed-loop system or by subjects usual insulin pump therapy in random order. A total of up to 34 adults (aiming for 24 completed subjects) aged 18 years and older with T1D on insulin pump therapy and HbA1C<7.5% will be recruited through diabetes clinics and other established methods in participating centers. 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 time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
closed loop glucose control, hypoglycemia, type 1 diabetes, HbA1C<7.5%

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
day and night closed loop control
Arm Type
Experimental
Arm Description
Subjects glucose levels are controlled by Florence D2A or similar closed loop insulin delivery system
Arm Title
usual insulin pump therapy management
Arm Type
Active Comparator
Arm Description
Subject glucose level controlled by usual insulin pump therapy in conjunction with continuous glucose monitoring (FreeStyle Navigator CGM)
Intervention Type
Device
Intervention Name(s)
Florence D2A or similar closed loop glucose control system
Intervention Description
Subject's glucose level will be controlled by the Florence D2A or similar automated closed loop glucose control system. The system comprises of FreeStyle Navigator 2 ® Continuous Glucose Monitoring (CGM) System (Abbott Diabetes Care, Alameda, CA, USA), Dana R Diabecare subcutaneous insulin infusion pump (Sooil Corp. Seoul, South Korea)or similar insulin pump, and MPC-based glucose control algorithm running on a smartphone
Intervention Type
Device
Intervention Name(s)
CSII with CGM
Intervention Description
Subject glucose level controlled by usual insulin pump therapy in conjunction with continuous glucose monitoring (CGM)
Primary Outcome Measure Information:
Title
Time spent in the target glucose range (3.9 to 10.0 mmol/l) based on subcutaneous glucose monitoring
Description
Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) during the 4 weeks of home stay. Intention to treat basis.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Continuous subcutaneous glucose monitoring (CGM) based outcome
Description
Time spent above and below the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) during the 4 weeks of home stay. Intention to treat basis.
Time Frame
4 weeks
Title
Continuous subcutaneous glucose monitoring (CGM) based outcome
Description
Average,standard deviation and coefficient of variation of glucose levels during 4 weeks of home periods
Time Frame
4 weeks
Title
Continuous subcutaneous glucose monitoring (CGM) based outcome
Description
The time with glucose levels < 3.5 mmol/l and <2.8 mmol/l during 4 weeks of home periods
Time Frame
4 weeks
Title
Continuous subcutaneous glucose monitoring (CGM) based outcome
Description
The time with glucose levels in the significant hyperglycaemia,(glucose levels > 16.7 mmol/l during 4 weeks of home periods
Time Frame
4 weeks
Title
Continuous subcutaneous glucose monitoring (CGM) based outcome
Description
Low Blood Glucose Index
Time Frame
4 weeks
Title
Continuous subcutaneous glucose monitoring (CGM) based outcome
Description
The "Area Under the Curve" below 3.5 mmol/l during 4 weeks home periods
Time Frame
4 weeks
Title
Continuous subcutaneous glucose monitoring (CGM) based outcome
Description
Between 24 hour period variability: Coefficient of variation of CGM glucose between 24 hour periods (midnight to midnight)
Time Frame
4 weeks
Title
Continuous subcutaneous glucose monitoring (CGM) based outcome during overnight period between 24:00 and 06:00
Description
Time spent with CGM glucose concentration in range 3.9-10.0mmol/L
Time Frame
4 weeks
Title
Continuous subcutaneous glucose monitoring (CGM) based outcome during day period between 06:00 to 24:00
Description
Time spent with CGM glucose concentration in the target range (3.9-10.0mmol/L)
Time Frame
4 weeks
Title
Insulin dose
Description
Total, basal and bolus insulin dose during 4 weeks of home periods
Time Frame
4 weeks
Title
Adverse Events
Description
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
Time Frame
5 months
Title
Utility Evaluation
Description
Utility evaluation is the percentage of closed-loop operation time during use at home, and when CGM was available
Time Frame
4 weeks
Other Pre-specified Outcome Measures:
Title
Accuracy of CGM
Description
CGM accuracy during 4 weeks home period; Capillary glucose vs. CGM will be evaluated using standard measures of numerical and clinical accuracy including absolute relative deviation and error grid analysis
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 insulin analogues (Insulin Aspart, Insulin Lispro or Insulin Glulisine) HbA1c <7.5% (58mmol/mmol) based on analysis from central laboratory or equivalent The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 6 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 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. Exclusion Criteria: Non-type 1 diabetes mellitus 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 Subjects with clinically significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator Significantly reduced hypoglycaemia awareness as judged by the investigator More than one episode of severe hypoglycaemia as defined by American Diabetes Association in preceding 6 months (Severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions). Random C-peptide > 100pmol/l with concomitant plasma glucose >4 mM(72 mg/dl) Total daily insulin dose > 2 IU/kg/day Subject is pregnant or breast feeding or planning pregnancy in near future (within next 3 months) Severe visual impairment Severe hearing impairment Subjects using implanted internal pacemaker Lack of reliable telephone facility for contact Subject not proficient in English (UK) or German (Austria) Subjects who are living alone Additional exclusion criteria specific for Austria: Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates). Additional exclusion criteria specific for Austria:Positive alcohol breath test.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roman Hovorka
Organizational Affiliation
University of Cambridge
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Graz
City
Graz
ZIP/Postal Code
A8036
Country
Austria
Facility Name
Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28094136
Citation
Bally L, Thabit H, Kojzar H, Mader JK, Qerimi-Hyseni J, Hartnell S, Tauschmann M, Allen JM, Wilinska ME, Pieber TR, Evans ML, Hovorka R. Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study. Lancet Diabetes Endocrinol. 2017 Apr;5(4):261-270. doi: 10.1016/S2213-8587(17)30001-3. Epub 2017 Jan 14.
Results Reference
derived

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Closing the Loop in Adults With Type 1 Diabetes and HbA1C<7.5% Under Free Living Conditions

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