EIT Health Innovation Project
CLOSE

CLOSE – Automated glucose control at home for people with chronic disease

CLOSE is the acronym for Automated Glucose Control at Home for People with Chronic Disease. It is one of the first EIT Health Innovation Projects and provides a paradigm example for implementing the EIT knowledge triangle integrating technology advancement, education and business creation.

CLOSE develops and deploys integrated solutions for persons with type 2 diabetes centered on Automated Insulin Delivery, also known as artificial pancreas (AP). CLOSE tailors the AP system to the needs of persons with type 2 diabetes and complements the device by offering obligatory trainings as well as outcome predictors and performance indicators (APplus).

By developing superior risk-benefit and cost-benefit scenarios for AP operation in type 2 diabetes, CLOSE aims to achieve positive acceptance by users and caregivers and a high eligibility for reimbursement. CLOSE is going to initially launch an APplus product and service package in the framework of French homecare service provision.

CLOSE co-creation and scalability

CLOSE is the first AP business initiative directly targeting persons with type 2 diabetes. Using a co-creation approach, CLOSE is going to develop superior risk-benefit and cost-benefit scenarios for AP operation in type 2 diabetes, thereby achieving positive acceptance by users and caregivers and a high eligibility for reimbursement.

CLOSE is unique in operating at the heart of a real-world homecare service provision ecosystem, paving the roads between prescribers, patients and payers. CLOSE currently conducts a multi-center clinical trial (NCT04233229) for the real-world assessment of glycemic effectiveness, patient-reported outcome measures (PROMs), as well as economic and process-related endpoints.

Following the initial launch of APplus in France CLOSE will scale up the APplus business by pursuing geographic distribution, targeting additional audiences and enhancing AP functionalities and interconnectedness.

The conception and design of the CLOSE project was recently explained in a peer-reviewed article and discussed by internationally renowned experts from NIH.

References

  1. Schliess F, Heise T, Benesch C, Mianowska B, Stegbauer C, Broge B, Gillard P, Binkley G, Crône V, Carlier S, Delval C, Petkov A, Beck JP, Lodwig V, Gurdala M, Szecsenyi J, Rosenmöller M, Cypryk K, Mathieu C, Renard E, Heinemann L. Artificial Pancreas Systems for People With Type 2 Diabetes: Conception and Design of the European CLOSE Project. J Diabetes Sci Technol 13(2):261-267, 2019
  1. Bremer AA, Arreaza-Rubín G. Analysis of “Artificial Pancreas (AP) Systems for People With Type 2 Diabetes: Conception and Design of the European CLOSE Project”. J Diabetes Sci Technol 13(2):268-270, 2019
  1. Interview: CLOSE crosses EIT Health pillars to ‘close the loop’ for diabetes patients. EIT Health News

Figure 1: The artificial pancreas (AP) core system approaches a “technical cure” of diabetes by closing the loop between blood glucose levels and insulin infusion when the continuous subcutaneous insulin infusion (CSII) rates are varied by a control algorithm (CONT) taking changes in glucose levels into account. The algorithm can be implemented in a smart phone. The communication between the components can be established via Bluetooth. Real-time glucose levels are measured continuously in the interstitial fluid by a glucose sensor (CGM).

Figure 2: APplus product and service package for people with T2D on homecare (French APplus paradigm). APplus comprises the AP, obligatory training and education modules, and a panel of outcome predictors and performance indicators helping to identify patients who might benefit most from AP usage and to measure the impact of AP usage on the quality and effectiveness of diabetes care.

CLOSE comprises a pan-European consortium

The consortium behind CLOSE is diverse and mutually reinforcing. Profil GmbH – a full-service CRO for early clinical trials in diabetes, obesity and cardiometabolic disease – coordinates the CLOSE initiative in collaboration with Air Liquide Healthcare and is supported by EURICE GmbH. Profil GmbH is a co-founder of the EIT Health Knowledge and Innovation Community – the network of top-of-the-range health innovators supported by the European Union.

CLOSE partners hold key capabilities in healthcare service provision, AP development and clinical evaluation, education & training, performance measurement, as well as at market implementation and advancement of diabetes technologies. In addition, expertise in healthcare research, economic modelling, and the development of performance measurement instruments is available within the partnership. The CLOSE partnership has been established and received funding under the umbrella of EIT Health. There are close collaborations with other European initiatives including D4Kids, D4Teens, AP@home, and RealWorld4Clinic.

CLOSE Partners:
Profil, Profil Mainz, Air Liquide Healthcare, Sanofi, Catholic University of Leuven, Medical University of Lodz, IESE Business School, aQua Institute, European Research and Project Office (EURICE).

CLOSE Advisory Board:
CLOSE receives valuable advice from the CLOSE Advisory Board members Prof. Dr Eric Renard (Centre Hospitalier Universitaire de Montpellier, Department of Endocrinology, Diabetes and Nutrition), Prof. Dr Yves Reznik (Centre Hospitalier Universitaire de Caen, Service d’Endocrinologie) and Prof. Dr Lutz Heinemann (Science Consulting in Diabetes GmbH).

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Prof. Dr. Freimut Schliess

Director Science & Innovation Profil Institut für Stoffwechselforschung GmbH

Publications 2011-2018

2019

Schliess F, Heise T, Benesch C, Mianowska B, Stegbauer C, Broge B, Gillard P, Binkley G, Crône V, Carlier S, Delval C, Petkov A, Beck JP, Lodwig V, Gurdala M, Szecsenyi J, Rosenmöller M, Cypryk K, Mathieu C, Renard E, Heinemann L. Artificial Pancreas Systems for People With Type 2 Diabetes: Conception and Design of the European CLOSE Project. J Diabetes Sci Technol. 13(2):261-267, 2019

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Benesch C, Kuhlenkötter M, Heise T. Considering blood dilution improves the precision of continuous whole blood glucose measurements. J. Diabetes Sci. Technol. 13(4):751-755, 2019

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Hövelmann U, Braendholt OM, Mouritzen U, Lamers D, Kronshage B, Heise T. Low doses of dasiglucagon consistently increase plasma glucose levels from hypoglycaemia and euglycaemia in people with type 1 diabetes mellitus. Diabetes Obes. Metab. 21(3):601-610, 2019

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Dovc K, Boughton C, Tauschmann M, Thabit H, Bally L, Allen JM., Acerini CL, Arnolds S, de Beaufort C, Bergenstal RM, Campbell F, Criego A, Dunger DB, Elleri D, Evans ML, Fröhlich-Reiterer E, Hofer S, Kapellen T, Leelarathna L, Pieber TR, Shah VN, Carlson AL. Bergenstal, RM, Evans ML, Hovorka R, AP@home04 and APCam11 consortia. Young children have higher variability of insulin requirements: observations during hybrid closed-loop insulin delivery. Diabetes Care 42(7):1344-1347, 2019

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Halberg IB, Lyby K, Wassermann K, Heise T, Zijlstra E, Plum-Mörschel L. Efficacy and safety of oral basal insulin versus subcutaneous insulin glargine in type 2 diabetes: a randomised, double-blind, phase 2 trial. Lancet Diabetes Endocrinol. 7(3):179-188, 2019

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Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G, Mathieu C, D’Alessio DA, Davies MJ. 2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 63(2):221-228.

2018

Zijlstra E. Analysis of “Laboratory and Benchtop Performance of a Mealtime Insulin Delivery System” J Diabetes Sci Technol. 2018 Apr 1:1932296818767940. doi: 10.1177/1932296818767940. [Epub ahead of print]

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Zijlstra E, Coester HV, Heise T, Plum-Mörschel L, Rasmussen O, Rikte T, Pedersen LK, Qvist M, Sparre T. Injecting without pressing a button: An exploratory study of a shield-triggered injection mechanism. Diabetes Obes Metab. 2018 May;20(5):1140-1147. doi: 10.1111/dom.13203.

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Zijlstra E, Jahnke J, Fischer A, Kapitza C, Forst T. Impact of injection speed, volume, and site on pain sensation. J Diabetes Sci Technol. 2018 Jan;12(1):163-168. doi: 10.1177/1932296817735121.

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Zijlstra E, Demissie M, Graungaard T, Heise T, Nosek L, Bode B. Investigation of pump compatibility of fast-acting insulin aspart in subjects with type 1 diabetes. J Diabetes Sci Technol. 2018 Jan;12(1):145-151. doi: 10.1177/1932296817730375.

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Ruan Y, Bally L, Thabit H, Leelarathna L, Hartnell S, Tauschmann M, Wilinska ME, Evans ML, Mader JK, Kojzar H, Dellweg S, Benesch C, Arnolds S, Pieber TR, Hovorka R. Hypoglycaemia incidence and recovery during home use of hybrid closed-loop insulin delivery in adults with type 1 diabetes Diabetes Obes Metab. 2018 Mar 25. doi: 10.1111/dom.13304. [Epub ahead of print]

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Bally L, Thabit H, Ruan Y, Mader JK, Kojzar H, Dellweg S, Benesch C, Hartnell S, Leelarathna L, Wilinska ME, Evans ML, Arnolds S, Pieber TR, Hovorka R. Bolusing frequency and amount impacts glucose control during hybrid closed-loop. Diabet Med. 2018 Mar;35(3):347-351. doi: 10.1111/dme.

2017

Emami A, Willinska ME, Thabit H, Leelarathna L, Hartnell S, Dellweg S, Benesch C, Mader JK, Holzer M, Kojzar H, Pieber TR, Arnolds S, Evans ML, Hovorka R. Behavioral patterns and associations with glucose control during 12-week randomized free-living clinical trial of day and night hybrid closed-loop insulin delivery in adults with type 1 diabetes. Diabetes Technol Ther. 2017 Jul;19(7):433-437. doi: 10.1089/dia.2016.0307.

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Ruan Y, Thabit H, Leelarathna L, Hartnell S, Wilinska ME, Tauschmann M, Dellweg S, Benesch C, Mader JK, Holzer M, Kojzar H, Evans ML, Pieber TR, Arnolds S, Hovorka R; AP@home consortium. Faster insulin action is associated with improved glycaemic outcomes during closed-loop insulin delivery and sensor-augmented pump therapy in adults with type 1 diabetes. Diabetes Obes Metab. 2017 Oct;19(10):1485-1489. doi: 10.1111/dom.12956.

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Barnard KD, Wysocki T, Ully V, Mader JK, Pieber TR, Thabit H, Tauschmann M, Leelarathna L, Hartnell S, Acerini CL, Wilinska ME, Dellweg S, Benesch C, Arnolds S, Holzer M, Kojzar H, Campbell F, Yong J, Pichierri J, Hindmarsh P, Heinemann L, Evans ML, Hovorka R. Closing the loop in adults, children and adolescents with suboptimally controlled type 1 diabetes under free living conditions: a Psychosocial substudy. J Diabetes Sci Technol. 2017 Nov;11(6):1080-1088. doi: 10.1177/1932296817702656.

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Kuhlenkötter M, Heise T, Benesch C. Improved algorithm for automated glucose clamps. Diabetes Technol Ther. 2017 Feb;19(2):124-130. doi: 10.1089/dia.2016.0355.

2016

Zijlstra E, Heinemann L, Fischer A, Kapitza C. A comprehensive performance evaluation of five blood glucose systems in the hypo-, eu-, and hyperglycemic range. J Diabetes Sci Technol. 2016 Nov 1;10(6):1316-1323.

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Heise T, Zijlstra E, Nosek L, Rikte T, Haahr H. Pharmacological properties of faster-acting insulin aspart vs insulin aspart in patients with type 1 diabetes receiving continuous subcutaneous insulin infusion: a randomized, double-blind, crossover trial. Diabetes Obes Metab. 2017 Feb;19(2):208-215. doi: 10.1111/dom.12803.

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Leelarathna L, Thabit H, Hartnell S, Willinska ME, Dellweg S, Benesch C, Mader JK, Holzer M, Kojzar H, Evans ML, Arnolds S, Pieber TR, Hovorka R; AP@home Consortium. Rapid benefits of structured optimization and sensor-augmented insulin pump therapy in adults with type 1 diabetes. Diabetes Sci Technol. 2017 Jan;11(1):180-181. doi: 10.1177/1932296816654715.

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Heise T, Zijlstra E, Nosek L, Heckermann S, Plum-Mörschel L, Forst T. Euglycaemic glucose clamp: what it can and cannot do, and how to do it. Diabetes Obes Metab. 2016 Oct;18(10):962-72. doi: 10.1111/dom.12703.

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Maahs DM, Buckingham BA, Castle JR, Cinar A, Damiano ER, Dassau E, DeVries JH, Doyle FJ 3rd, Griffen SC, Haidar A, Heinemann L, Hovorka R, Jones TW, Kollman C, Kovatchev B, Levy BL, Nimri R, O’Neal DN, Philip M, Renard E, Russell SJ, Weinzimer SA, Zisser H, Lum JW. Outcome measures for artificial pancreas clinical trials: a consensus report. Diabetes Care. 2016 Jul;39(7):1175-9. doi: 10.2337/dc15-2716.

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Heinemann L, Benesch C, DeVries JH; AP@home Consortium. AP@home: the artificial pancreas is now at home.Diabetes Sci Technol. 2016 Jun 28;10(4):950-8. doi: 10.1177/1932296816632002.

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Ruan Y, Thabit H, Leelarathna L, Hartnell S, Willinska ME, Dellweg S, Benesch C, Mader JK, Holzer M, Kojzar H, Evans ML, Pieber TR, Arnolds S, Hovorka R; AP@home Consortium. Variability of insulin requirements over 12 weeks of closed-loop insulin delivery in adults with type 1 diabetes. Diabetes Care. 2016 May;39(5):830-2. doi: 10.2337/dc15-2623.

2015

Thabit H, Tauschmann M, Allen JM, Leelarathna L, Hartnell S, Wilinska ME, Acerini CL, Dellweg S, Benesch C, Heinemann L, Mader JK, Holzer M, Kojzar H, Exall J, Yong J, Pichierri J, Barnard KD, Kollman C, Cheng P, Hindmarsh PC, Campbell FM, Arnolds S, Pieber TR, Evans ML, Dunger DB, Hovorka R. Home use of an artificial beta cell in type 1 diabetes. N Engl J Med. 2015 Nov 26;373(22):2129-2140. doi: 10.1056/NEJMoa1509351.

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Benesch C, Heise T, Klein O, Heinemann L, Arnolds S. How to assess the quality of glucose clamps? Evaluation of clamps performed with ClampArt, a novel automated clamp device. J Diabetes Sci Technol. 2015 Jul;9(4):792-800. doi: 10.1177/1932296815576957.

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Arnolds S, Heckermann S, Heise T, Sawicki PT. Spectrum of diabetes research does not reflect patients’ scientific preferences: a longitudinal evaluation of diabetes research areas 2010-2013 vs. a cross-sectional survey in patients with diabetes. Exp Clin Endocrinol Diabetes. 2015 May;123(5):299-302. doi: 10.1055/s-0034-1398591.

2014

Leelarathna L, Dellweg S, Mader JK, Barnard K, Benesch C, Ellmerer M, Heinemann L, Kojzar H, Thabit H, Wilinska ME, Wysocki T, Pieber TR, Arnolds S, Evans ML, Hovorka R; AP@home consortium. Assessing the effectiveness of 3 months day and night home closed-loop insulin delivery in adults with suboptimally controlled type 1 diabetes: a randomised crossover study protocol. BMJ Open. 2014 Sep 3;4(9):e006075. doi: 10.1136/bmjopen-2014-006075.

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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.

2013

Luijf YM, DeVries JH, Zwinderman K, Leelarathna L, Nodale M, Caldwell K, Kumareswaran K, Elleri D, Allen JM, Wilinska ME, Evans ML, Hovorka R, Doll W, Ellmerer M, Mader JK, Renard E, Place J, Farret A, Cobelli C, Del Favero S, Dalla Man C, Avogaro A, Bruttomesso D, Filippi A, Scotton R, Magni L, Lanzola G, Di Palma F, Soru P, Toffanin C, De Nicolao G, Arnolds S, Benesch C, Heinemann L; AP@home Consortium. Day and night closed-loop control in adults with type 1 diabetes: a comparison of two closed-loop algorithms driving continuous subcutaneous insulin infusion versus patient self-management. Diabetes Care. 2013 Dec;36(12):3882-7. doi: 10.2337/dc12-1956.

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Luijf YM, Arnolds S, Avogaro A, Benesch C, Bruttomesso D, Farret A, Heinemann L, Place J, Renard E, Scotton R, DeVries JH; AP@home consortium. Patch pump versus conventional pump: postprandial glycemic excursions and the influence of wear time. Diabetes Technol Ther. 2013 Jul;15(7):575-9. doi: 10.1089/dia.2013.0016.

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Luijf YM, Mader JK, Doll W, Pieber T, Farret A, Place J, Renard E, Bruttomesso D, Filippi A, Avogaro A, Arnolds S, Benesch C, Heinemann L, DeVries JH; AP@home consortium. Accuracy and reliability of continuous glucose monitoring systems: a head-to-head comparison. Diabetes Technol Ther. 2013 Aug;15(8):722-7. doi: 10.1089/dia.2013.0049.

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Arnolds S, Heckermann S, Koch C, Heissmann N, Sawicki PT. How do patients’ preferences compare to the present spectrum of diabetes research? Exp Clin Endocrinol Diabetes. 2013 Jan;121(1):60-3. doi: 10.1055/s-0032-1323776.

2011

Heinemann L, Benesch C, DeVries JH. AP@home: a novel European approach to bring the artificial pancreas home. J Diabetes Sci Technol. 2011 Nov 1;5(6):1363-72.