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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: Florence D2A or similar closed loop glucose control system; Device: CSII with CGM

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, A8036
    • Medical University of Graz
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: day and night closed loop control; Subjects glucose levels are controlled by Florence D2A or similar closed loop insulin delivery system	Device: Florence D2A or similar closed loop glucose control system; 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
ACTIVE_COMPARATOR: usual insulin pump therapy management; Subject glucose level controlled by usual insulin pump therapy in conjunction with continuous glucose monitoring (FreeStyle Navigator CGM)	Device: CSII with CGM; Subject glucose level controlled by usual insulin pump therapy in conjunction with continuous glucose monitoring (CGM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks
Continuous subcutaneous glucose monitoring (CGM) based outcome	Average,standard deviation and coefficient of variation of glucose levels during 4 weeks of home periods	4 weeks
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	4 weeks
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	4 weeks
Continuous subcutaneous glucose monitoring (CGM) based outcome	Low Blood Glucose Index	4 weeks
Continuous subcutaneous glucose monitoring (CGM) based outcome	The "Area Under the Curve" below 3.5 mmol/l during 4 weeks home periods	4 weeks
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)	4 weeks
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	4 weeks
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)	4 weeks
Insulin dose	Total, basal and bolus insulin dose during 4 weeks of home periods	4 weeks
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	5 months
Utility Evaluation	Utility evaluation is the percentage of closed-loop operation time during use at home, and when CGM was available	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of CGM	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	4 weeks

Collaborators and Investigators

• Sponsor: University of Cambridge
• Collaborators: Medical University of Graz

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ACTUAL): October 1, 2016
• Study Completion (ACTUAL): October 1, 2016

Study Registration Dates

• First Submitted: March 29, 2016
• First Submitted That Met QC Criteria: March 29, 2016
• First Posted (ESTIMATE): April 4, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): October 11, 2016
• Last Update Submitted That Met QC Criteria: October 9, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: hypoglycemia; type 1 diabetes; closed loop glucose control; HbA1C<7.5%
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: AP@home04 phase2