Short Term Closed-loop Glucose Control in Adults With Type 1 Diabetes

NCT01666028 | Completed Phase 2

• 1 other identifier: AP@home02
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 3

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.

Conditions

Type 1 Diabetes

Keywords

Type 1 Diabetes; Closed Loop glucose control; Artificial Pancreas; CSII; CGM

Outcome Measures

Primary Outcomes (1)

• 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.

  7 day home study period

Secondary Outcomes (7)

• Time spent above and below the target glucose (3.9 to 10.0 mmol/l) based on continuous subcutaneous glucose monitoring (CGM)

  7 day home study period

• Average and standard deviation glucose levels based on continuous subcutaneous glucose monitoring

  7 day home study period

• The time with glucose levels < 3.5 mmol/l and <2.8 mmol/l based on continuous subcutaneous glucose monitoring

  7 Day home study period

• The time with glucose levels in the significant hyperglycaemia, as based on continuous subcutaneous glucose monitoring (glucose levels > 16.7 mmol/l)

  7 day home study period

• Low Blood Glucose Index (LBGI) based on continuous subcutaneous glucose monitoring

  7 day Home study period

Other Outcomes (1)

• Duration of use of the closed-loop system at home.

  7 days

Study Arms (2)

Closed Loop Glucose control

EXPERIMENTAL

Subject's glucose level is controlled by the automated closed loop glucose control system

Device: FlorenceD or similar closed loop glucose control system

CSII with real-time CGM

ACTIVE COMPARATOR

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

Device: CSII with real-time CGM

Interventions

FlorenceD or similar closed loop glucose control system DEVICE

Subject's glucose level will be controlled by the FlorenceD or similar automated closed loop glucose control system. The system comprises of FreeStyle Navigator® 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 portable computer.

Closed Loop Glucose control

CSII with real-time CGM DEVICE

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

CSII with real-time CGM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 3 months currently using insulin Aspart, with good knowledge of insulin self-adjustment including carbohydrate counting
• HbA1c ≤ 10 % based on analysis from local laboratory
• 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
• 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 literate in English
• 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.

You may not qualify if:

• 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
• Total daily insulin dose more than 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
• Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
• Positive alcohol breath test.
• 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

Sponsors & Collaborators

• University of Cambridge: lead
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• Profil Institut für Stoffwechselforschung GmbH: collaborator
• Medical University of Graz: collaborator

Study Sites (3)

Medical University of Graz

Graz, A- 8036, Austria

Location

Profil Institut für Stoffwechselforschung GmbH

Neuss, D-41460, Germany

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 20138357 BACKGROUND

• 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.

  PMID: 21493665 BACKGROUND

• 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.

  PMID: 26241693 DERIVED

• 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.

  PMID: 24963110 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Mark Evans, FRCP (UK) MD

  University of Cambridge

  PRINCIPAL INVESTIGATOR

• Sabine Arnolds, MD

  Profil Institut für Stoffwechselforschung GmbH

  PRINCIPAL INVESTIGATOR

• Thomas Pieber, MD

  Medical University of Graz

  PRINCIPAL INVESTIGATOR

• Roman Hovorka, PhD

  University of Cambridge

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Research Associate

Study Record Dates

• First Submitted: August 9, 2012
• First Posted: August 16, 2012
• Study Start: November 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: December 2, 2014

Record last verified: 2014-12

Locations

AU (1); DE (1); GB (1)