@article{9fb19a017492408ab809e7423201ce84,
title = "Twelve-week 24/7 ambulatory artificial pancreas with weekly adaptation of insulin delivery settings: Effect on hemoglobin A1c and hypoglycemia",
abstract = "Objective: Artificial pancreas (AP) systems are best positioned for optimal treatment of type 1 diabetes (T1D) and are currently being tested in outpatient clinical trials. Our consortium developed and tested a novel adaptive AP in an outpatient, single-arm, uncontrolled multicenter clinical trial lasting 12 weeks. Research Design and Methods: Thirty adults with T1D completed a continuous glucose monitor (CGM)-augmented 1-week sensor-augmented pump(SAP) period. After the AP was started, basal insulin delivery settings used by the AP for initialization were adapted weekly, and carbohydrate ratios were adapted every 4 weeks by an algorithm running on a cloud-based server, with automatic data upload from devices. Adaptations were reviewed by expert study clinicians and patients. The primary end point was change in hemoglobin A1c (HbA1c). Outcomes are reported adhering to consensus recommendations on reporting of AP trials. Results: Twenty-nine patients completed the trial. HbA1c, 7.0 ± 0.8% at the start of AP use, improved to 6.7 ± 0.6% after 12 weeks (-0.3, 95% CI -0.5 to -0.2, P < 0.001). Compared with the SAP run-in, CGM time spent in the hypoglycemic range improved during the day from 5.0 to 1.9%(-3.1, 95% CI -4.1 to -2.1, P < 0.001) and overnight from 4.1 to 1.1% (-3.1, 95% CI -4.2 to -1.9, P < 0.001). Whereas carbohydrate ratios were adapted to a larger extent initially with minimal changes there after, basal insulin was adapted throughout. Approximately 10% of adaptation recommendations were manually overridden. There were no protocol-related serious adverse events. Conclusions: Use of our novel adaptive AP yielded significant reductions in HbA1c and hypoglycemia.",
author = "Eyal Dassau and Pinsker, {Jordan E.} and Kudva, {Yogish C.} and Brown, {Sue A.} and Ravi Gondhalekar and Man, {Chiara Dalla} and Steve Patek and Michele Schiavon and Vikash Dadlani and Isuru Dasanayake and Church, {Mei Mei} and Carter, {Rickey E.} and Bevier, {Wendy C.} and Huyett, {Lauren M.} and Jonathan Hughes and Stacey Anderson and Dayu Lv and Elaine Schertz and Emma Emory and McCrady-Spitzer, {Shelly K.} and Tyler Jean and Bradley, {Paige K.} and Ling Hinshaw and {Laguna Sanz}, {Alejandro J.} and Ananda Basu and Boris Kovatchev and Claudio Cobelli and Doyle, {Francis J.}",
note = "Funding Information: The funders and device manufacturers had no influence on the design or conduct of the trial and were not involved in data collection or analysis, the writing of the manuscript, or the decision to submit it for publication. Duality of Interest. E.D. has received consulting fees from Animas and Insulet; has received research support from Dexcom, Insulet, Roche, Xeris, and Animas; and receives royalty payments on intellectual property related to the MPC algorithm used. J.E.P. has conducted AP research sponsored by Insulet and Bigfoot and has received product support to his institution from Animas, Lifescan, Roche, and Dexcom. Y.C.K. has performed studies for Medtronic and has received product support from Dexcom, Roche, and Tandem. S.A.B. reports materials support from Roche Diagnostics and Dexcom, grants and material support from Animas Corporation, and grants from Medtronic outside the submitted work. R.G. receives royalty payments on intellectual property related to the MPC algorithm used in this study. S.P. is a shareholder of TypeZero Technologies. S.A. reports support from Dexcom and Roche Diagnostics, grants from Medtronic, personal fees from Senseonics, and grants from InSpark outside the submitted work. A.B. has received research support from Novo Nordisk, Tandem, and AstraZeneca. B.K. has patents and patent applications related to diabetes technology managed by the University of Virginia Licensing and Ventures group; has received grant/research support managed by the University of Virginia from Dexcom, Roche Diabetes Care, Sanofi, and Tandem Diabetes Care; has received advisory board/ consultant/speakers{\textquoteright} bureau fees for Dexcom, Sanofi, and Senseonics; and cofounded and is a shareholder of TypeZero Technologies. C.C. reports 10 patents and patent applications related to glucose sensors and AP; nonfinancial support from Roche and Dexcom; and research support managed by the University of Padova from Dexcom, Sanofi, and Adocia and is on an advisory panel for Novo Nordisk. F.J.D. has received consulting fees from Mode AGC; has received research support from Dexcom, Insulet, Roche, and Xeris; and receives royalty payments on intellectual property related to the MPC algorithm used in this study. No other potential conflicts of interest relevant to this article were reported. Author Contributions. E.D., J.E.P., Y.C.K., S.A.B., R.G., C.D.M., S.P., M.S., A.B., B.K., C.C., and F.J.D. helped design the study protocol, contributed to the technology design, ensured the regulatory approval of the CLC system, provided primary technical and clinical support on site during all sessions, analyzed data, and authored the manuscript. E.D., R.G., C.D.M., S.P., M.S., I.D., L.M.H., J.H., D.L., E.S., A.J.L.S., C.C., and F.J.D. contributed to the technology design of the CLC system, aided in data acquisition and analysis, and edited and revised the manuscript. E.D., R.G., I.D., and E.S. helped construct the controller infrastructure, contributed to the discussion, and reviewed and edited themanuscript.J.E.P.,Y.C.K.,S.A.B.,S.P.,V.D.,M.M.C., W.C.B., J.H., S.A., D.L., E.E., S.K.M.-S., T.J., P.K.B., L.H., andA.B.conductedtheclinicaltrials,researcheddata, and reviewed and edited the manuscript. R.E.C. performed the statistical analysis and contributed to writing and reviewing of the manuscript. F.J.D. edited and reviewed the manuscript and was the principal investigator of the project. F.J.D. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in abstract form at the 10th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD), Paris, France, 15–18 February 2017. Funding Information: Data and Safety Monitoring Board: Dr. Trang T. Ly, (chair) (Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Stanford UniversitySchoolofMedicine),Dr.DavidM.Maahs (Barbara Davis Center, University of Colorado Denver), and Dr. Danielle Gianferante (Type 1 Diabetes Exchange). Funding. This study was supported by grants from the National Institutes of Health National Institute of DiabetesandDigestive andKidneyDiseases(DP3-DK-094331) and the National Center for Advancing Translational Science (UL1-TR-000135) and by the Urdang Family Foundation to MayoClinic.C.C., C.D.M., and M.S. are partially supported by Italian Ministero dell{\textquoteright}Universit{\`a} e della Ricerca Scientifica (Progetto di Ateneo dell{\textquoteright}Universit{\`a} di Padova 2014). Roche Diabetes Care (Indianapolis, IN) supplied all insulin pumps (Accu-Chek Spirit Combo) and additional supplies in-kind. Dexcom (San Diego, CA) provided a research discount on pricing on the CGM sensors, transmitters, and receivers (G4 Platinum with Share). Test strips (OneTouch Ultra Blue) were supplied by LifeScan in-kind, through support from the Investigator-Initiated Study Program of LifeScan. Publisher Copyright: {\textcopyright} 2017 by the American Diabetes Association.",
year = "2017",
month = dec,
day = "1",
doi = "10.2337/dc17-1188",
language = "English (US)",
volume = "40",
pages = "1719--1726",
journal = "Diabetes care",
issn = "0149-5992",
publisher = "American Diabetes Association Inc.",
number = "12",
}