Clinical trial NCT01666028: Short Term Closed-loop Glucose Control in Adults With Type 1 Diabetes
Official title: An Open-label, Three-centre, Randomised, Two-period Crossover Study to Assess the Safety, Efficacy and Utility of Automated Closed-loop Glucose Control in Comparison With Continuous Subcutaneous Insulin Infusion Combined With Continuous Glucose Monitoring in Adults With Type 1 Diabetes - A Combined Clinical Research Facility and Home Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Type 1 Diabetes
Closed Loop glucose control
Artificial Pancreas
CSII
CGM
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: Cambridge University Hospitals NHS Foundation Trust
name: Profil Institut für Stoffwechselforschung GmbH
name: Medical University of Graz
First posted: 2012-08-16
Enrollment: 18
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 the feasibility, efficacy and safety of automated closed-loop glucose control in the home setting over a short term period. The data and experienced gained from this study will be utilised in planning future home studies.

This is an open-label, three centre, randomised, crossover design, involving two, 8 day (first day in the clinical research facility and seven days at home) study periods during which glucose levels will be controlled either by an automated closed-loop system or by subjects usual insulin pump therapy in random order. A total of up to 24 adults (aiming for 18 completed subjects) aged 18 years and older with T1D on insulin pump therapy will be recruited through diabetes clinics and other established methods in participating centres.

Subjects will receive appropriate training in the safe use of closed-loop insulin delivery system. During the 24 hour in-patient stay subjects will be encouraged to mimic their usual day and will be allowed to walk inside hospital premises. Subjects will be advised to discontinue automated closed-loop insulin delivery and follow their usual insulin pump therapy for periods of strenuous exercise during the 7 day home study phase.

The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by CGM (adjusted for potential over-estimation) during home stay. Secondary outcomes are the time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics, and for the stay at the clinical research facility, time spent in the target range, above and below the target range as measured by plasma glucose.


Eligibility criteria: Inclusion Criteria:

1. The subject has type 1 diabetes as defined by WHO
2. The subject is 18 years of age or older
3. The subject will have been on an insulin pump for at least 3 months currently using insulin Aspart, with good knowledge of insulin self-adjustment including carbohydrate counting
4. HbA1c ≤ 10 % based on analysis from local laboratory
5. The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 6 measurements per day during the 7 day home phase of the study
6. The subject is willing to wear closed-loop system at home and at work place
7. The subject is willing to follow study specific instructions
8. The subject is literate in English
9. Female subjects of child bearing age should be on effective contraception and must have a negative urine-HCG pregnancy test at screening. In addition in Germany, women of childbearing potential must use a highly effective method of birth control, which is defined as those which result in a low failure rate (i.e. less than 1% per year) and must use two independent methods of contraception, e.g. diaphragm and spermicide-coated condom.

Exclusion Criteria:

1. Non-type 1 diabetes mellitus
2. Any other physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results
3. Current treatment with drugs known to have significant interference with glucose metabolism, such as systemic corticosteroids, as judged by the investigator
4. Known or suspected allergy against insulin
5. Subjects with clinically significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator
6. Significantly reduced hypoglycaemia awareness as judged by the investigator
7. Total daily insulin dose more than 2 IU/kg/day
8. Subject is pregnant or breast feeding or planning pregnancy in near future (within next 3 months)
9. Severe visual impairment
10. Severe hearing impairment
11. Subjects using implanted internal pacemaker
12. Lack of reliable telephone facility for contact

Additional exclusion criteria specific for Austria and Germany

1. Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
2. Positive alcohol breath test.

Additional exclusion criteria specific for Germany only

Positive reaction to any of the following tests: hepatitis B surface (HBs) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus (HIV) 1 antibodies, anti-HIV2 antibodies

-

Primary outcomes:
measure: Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) adjusted for sensor error.
timeFrame: 7 day home study period
Secondary outcomes:
measure: Time spent above and below the target glucose (3.9 to 10.0 mmol/l) based on continuous subcutaneous glucose monitoring (CGM)
timeFrame: 7 day home study period
measure: Average and standard deviation glucose levels based on continuous subcutaneous glucose monitoring
timeFrame: 7 day home study period
measure: The time with glucose levels < 3.5 mmol/l and <2.8 mmol/l based on continuous subcutaneous glucose monitoring
timeFrame: 7 Day home study period
measure: The time with glucose levels in the significant hyperglycaemia, as based on continuous subcutaneous glucose monitoring (glucose levels > 16.7 mmol/l)
timeFrame: 7 day home study period
measure: Low Blood Glucose Index (LBGI) based on continuous subcutaneous glucose monitoring
timeFrame: 7 day Home study period
measure: During 24 hour in-patient stay - Same glucose metrics as during 7 day home stay but calculated based on continuous subcutaneous glucose monitoring (CGM) and plasma glucose measurements.
timeFrame: 24 hours
measure: Number of episodes of hypoglycaemia, severe hypoglycaemia as well as nature and severity of any other adverse events.
timeFrame: 8 days
Other outcomes:
measure: Duration of use of the closed-loop system at home.
timeFrame: 7 days
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
state: Cambridgeshire
Study officials:
affiliation: University of Cambridge
name: Mark Evans, FRCP (UK) MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Profil Institut für Stoffwechselforschung GmbH
name: Sabine Arnolds, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of Graz
name: Thomas Pieber, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cambridge
name: Roman Hovorka, PhD
role: STUDY_DIRECTOR
References:
citation: Hovorka R, Allen JM, Elleri D, Chassin LJ, Harris J, Xing D, Kollman C, Hovorka T, Larsen AM, Nodale M, De Palma A, Wilinska ME, Acerini CL, Dunger DB. Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet. 2010 Feb 27;375(9716):743-51. doi: 10.1016/S0140-6736(09)61998-X. Epub 2010 Feb 4.
citation: Hovorka R, Kumareswaran K, Harris J, Allen JM, Elleri D, Xing D, Kollman C, Nodale M, Murphy HR, Dunger DB, Amiel SA, Heller SR, Wilinska ME, Evans ML. Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies. BMJ. 2011 Apr 13;342:d1855. doi: 10.1136/bmj.d1855.
citation: Thabit H, Leelarathna L, Wilinska ME, Elleri D, Allen JM, Lubina-Solomon A, Walkinshaw E, Stadler M, Choudhary P, Mader JK, Dellweg S, Benesch C, Pieber TR, Arnolds S, Heller SR, Amiel SA, Dunger D, Evans ML, Hovorka R. Accuracy of Continuous Glucose Monitoring During Three Closed-Loop Home Studies Under Free-Living Conditions. Diabetes Technol Ther. 2015 Nov;17(11):801-7. doi: 10.1089/dia.2015.0062. Epub 2015 Aug 4.
citation: Leelarathna L, Dellweg S, Mader JK, Allen JM, Benesch C, Doll W, Ellmerer M, Hartnell S, Heinemann L, Kojzar H, Michalewski L, Nodale M, Thabit H, Wilinska ME, Pieber TR, Arnolds S, Evans ML, Hovorka R; AP@home Consortium. Day and night home closed-loop insulin delivery in adults with type 1 diabetes: three-center randomized crossover study. Diabetes Care. 2014 Jul;37(7):1931-7. doi: 10.2337/dc13-2911.