Clinical trial NCT02727231: 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
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: closed loop glucose control
hypoglycemia
type 1 diabetes
HbA1C<7.5%
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: Medical University of Graz
First posted: 2016-04-04
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Time spent in the target glucose range (3.9 to 10.0 mmol/l) based on subcutaneous glucose monitoring
timeFrame: 4 weeks
Secondary outcomes:
measure: Continuous subcutaneous glucose monitoring (CGM) based outcome
timeFrame: 4 weeks
measure: Continuous subcutaneous glucose monitoring (CGM) based outcome
timeFrame: 4 weeks
measure: Continuous subcutaneous glucose monitoring (CGM) based outcome
timeFrame: 4 weeks
measure: Continuous subcutaneous glucose monitoring (CGM) based outcome
timeFrame: 4 weeks
measure: Continuous subcutaneous glucose monitoring (CGM) based outcome
timeFrame: 4 weeks
measure: Continuous subcutaneous glucose monitoring (CGM) based outcome
timeFrame: 4 weeks
measure: Continuous subcutaneous glucose monitoring (CGM) based outcome
timeFrame: 4 weeks
measure: Continuous subcutaneous glucose monitoring (CGM) based outcome during overnight period between 24:00 and 06:00
timeFrame: 4 weeks
measure: Continuous subcutaneous glucose monitoring (CGM) based outcome during day period between 06:00 to 24:00
timeFrame: 4 weeks
measure: Insulin dose
timeFrame: 4 weeks
measure: Adverse Events
timeFrame: 5 months
measure: Utility Evaluation
timeFrame: 4 weeks
Other outcomes:
measure: Accuracy of CGM
timeFrame: 4 weeks
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
state: Cambridgeshire
Study officials:
affiliation: University of Cambridge
name: Roman Hovorka
role: PRINCIPAL_INVESTIGATOR
References:
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.