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| ID | Type | Description | Link |
|---|---|---|---|
| 941481 | Other Grant/Funding Number | American Heart Association | |
| 3-SRA-2023-1236-M-B | Other Grant/Funding Number | Juvenile Diabetes Research Foundation |
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This study will examine the potential cardiovascular effect(s) of artificial pancreas (AP) technology in patients with type 1 diabetes. AP technology is a system of devices that closely mimics the glucose-regulating function of a healthy human pancreas. It includes an insulin pump and a continuous glucose monitor (CGM). In this study, the investigators will research whether improvements in blood glucose levels and blood glucose variability will in turn decrease biomarkers of inflammation and endothelial dysfunction while improving cardiovascular function.
Cardiovascular disease is a type of disease that affects the heart and blood vessels. The current care for cardiovascular disease prevention in people with type 1 diabetes is to manage blood pressure, cholesterol blood levels, or manage blood glucose levels.
This study will examine the potential cardiovascular effect(s) of artificial pancreas (AP) technology in patients with type 1 diabetes. AP technology is a system of devices that closely mimics the glucose-regulating function of a healthy human pancreas. It includes an insulin pump and a continuous glucose monitor (CGM). In this study, we will use the Food and Drug Administration (FDA)-approved Tandem t:slim insulin pump with Control-IQ Technology and the FDA approved Dexcom G6 CGM. This study will research whether improvements in blood glucose metrics lead to reductions in some of the cardiovascular biomarkers that represent harmful effects in people with type 1 diabetes. Subjects will be randomly assigned to one of two study groups for 12 weeks---Group 1 will be treated with AP Technology and Group 2 will wear the study CGM and continue to use their current diabetes management strategy (i.e., standard care).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Closed-loop artificial pancreas (AP) | Experimental | FDA approved Tandem t:slim insulin pump with Control-IQ Technology and the Dexcom G6 CGM |
|
| Sensor Augmented Pump (SAP) therapy | Experimental | Sensor augmented pump (SAP) therapy that includes the use of a study CGM and the participant's current insulin therapy (i.e., either insulin pump or multiple daily injections) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tandem t:slim X2 with Control-IQ Technology | Device | FDA approved Tandem t:slim insulin pump with Control-IQ Technology and the Dexcom G6 CGM |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glucose Time-in-Range | Time-in-range will measured by continuous glucose monitor device | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| High-sensitivity C-reactive protein (hs-CRP) | Inflammatory Biomarker | At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks |
| TNF-alpha | Inflammatory Biomarker |
| Measure | Description | Time Frame |
|---|---|---|
| Human CD14+CD16- monocytes | Proinflammatory immune cells associated with atherosclerosis | At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| William B Horton, MD | Contact | 434-924-1828 | WBH2N@uvahealth.org | |
| Lee Hartline, MEd | Contact | 434-924-5247 | lmh9d@virginia.edu |
| Name | Affiliation | Role |
|---|---|---|
| William B Horton, MD | University of Virginia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Virginia Health System | Recruiting | Charlottesville | Virginia | 22903 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23055834 | Background | Livingstone SJ, Looker HC, Hothersall EJ, Wild SH, Lindsay RS, Chalmers J, Cleland S, Leese GP, McKnight J, Morris AD, Pearson DW, Peden NR, Petrie JR, Philip S, Sattar N, Sullivan F, Colhoun HM. Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study. PLoS Med. 2012;9(10):e1001321. doi: 10.1371/journal.pmed.1001321. Epub 2012 Oct 2. | |
| 20739685 |
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| Sensor augmented pump (SAP) therapy | Device | Sensor augmented pump (SAP) therapy that includes the use of a study CGM and the participant's personal insulin pump |
|
| At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks |
| Interleukin-6 (IL-6) | Inflammatory Biomarker | At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks |
| E-selectin | Biomarker of endothelial dysfunction | At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks |
| Intracellular adhesion molecule 1 (ICAM-1) | Biomarker of endothelial dysfunction | At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks |
| Myocardial Perfusion (measured by contrast-enhanced ultrasound [CEU]) | CEU will be assessed before and during a euglycemic-hyperinsulinemic clamp | At baseline and 12 weeks of treatment |
| Carotid Femoral Pulse Wave Velocity (cfPWV) | Measurement of change in central aortic stiffness | At baseline and 12 weeks of treatment |
| Brachial artery flow-mediated dilation (FMD) | Measure of conduit artery endothelial function | At baseline and 12 weeks of treatment |
| Insulin sensitivity | insulin sensitivity will be assessed by M value during a euglycemic-hyperinsulinemic clamp | At baseline and 12 weeks of treatment |
| Background |
| Secrest AM, Becker DJ, Kelsey SF, Laporte RE, Orchard TJ. Cause-specific mortality trends in a large population-based cohort with long-standing childhood-onset type 1 diabetes. Diabetes. 2010 Dec;59(12):3216-22. doi: 10.2337/db10-0862. Epub 2010 Aug 25. |
| 25126392 | Background | Martin-Timon I, Sevillano-Collantes C, Segura-Galindo A, Del Canizo-Gomez FJ. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World J Diabetes. 2014 Aug 15;5(4):444-70. doi: 10.4239/wjd.v5.i4.444. |
| 29139080 | Background | Priya G, Kalra S. A Review of Insulin Resistance in Type 1 Diabetes: Is There a Place for Adjunctive Metformin? Diabetes Ther. 2018 Feb;9(1):349-361. doi: 10.1007/s13300-017-0333-9. Epub 2017 Nov 14. |
| 25441221 | Background | Alessa T, Szeto A, Chacra W, Mendez A, Goldberg RB. High HDL-C prevalence is common in type 1 diabetes and increases with age but is lower in Hispanic individuals. J Diabetes Complications. 2015 Jan-Feb;29(1):105-7. doi: 10.1016/j.jdiacomp.2014.08.011. Epub 2014 Sep 6. |
| 2401396 | Background | Norgaard K, Feldt-Rasmussen B, Borch-Johnsen K, Saelan H, Deckert T. Prevalence of hypertension in type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1990 Jul;33(7):407-10. doi: 10.1007/BF00404089. |
| 30060120 | Background | Corbin KD, Driscoll KA, Pratley RE, Smith SR, Maahs DM, Mayer-Davis EJ; Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON). Obesity in Type 1 Diabetes: Pathophysiology, Clinical Impact, and Mechanisms. Endocr Rev. 2018 Oct 1;39(5):629-663. doi: 10.1210/er.2017-00191. |
| 31295146 | Background | Kanter JE, Shao B, Kramer F, Barnhart S, Shimizu-Albergine M, Vaisar T, Graham MJ, Crooke RM, Manuel CR, Haeusler RA, Mar D, Bomsztyk K, Hokanson JE, Kinney GL, Snell-Bergeon JK, Heinecke JW, Bornfeldt KE. Increased apolipoprotein C3 drives cardiovascular risk in type 1 diabetes. J Clin Invest. 2019 Jul 11;129(10):4165-4179. doi: 10.1172/JCI127308. |
| 11595647 | Background | Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab. 2001 Nov;281(5):E924-30. doi: 10.1152/ajpendo.2001.281.5.E924. |
| 14578299 | Background | Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes. 2003 Nov;52(11):2795-804. doi: 10.2337/diabetes.52.11.2795. |
| 16453381 | Background | Piconi L, Quagliaro L, Assaloni R, Da Ros R, Maier A, Zuodar G, Ceriello A. Constant and intermittent high glucose enhances endothelial cell apoptosis through mitochondrial superoxide overproduction. Diabetes Metab Res Rev. 2006 May-Jun;22(3):198-203. doi: 10.1002/dmrr.613. |
| 19263033 | Background | Horvath EM, Benko R, Kiss L, Muranyi M, Pek T, Fekete K, Barany T, Somlai A, Csordas A, Szabo C. Rapid 'glycaemic swings' induce nitrosative stress, activate poly(ADP-ribose) polymerase and impair endothelial function in a rat model of diabetes mellitus. Diabetologia. 2009 May;52(5):952-61. doi: 10.1007/s00125-009-1304-0. Epub 2009 Mar 5. |
| 24128999 | Background | Frontoni S, Di Bartolo P, Avogaro A, Bosi E, Paolisso G, Ceriello A. Glucose variability: An emerging target for the treatment of diabetes mellitus. Diabetes Res Clin Pract. 2013 Nov;102(2):86-95. doi: 10.1016/j.diabres.2013.09.007. Epub 2013 Sep 25. |
| 25538320 | Background | Ayano-Takahara S, Ikeda K, Fujimoto S, Hamasaki A, Harashima S, Toyoda K, Fujita Y, Nagashima K, Tanaka D, Inagaki N. Glycemic variability is associated with quality of life and treatment satisfaction in patients with type 1 diabetes. Diabetes Care. 2015 Jan;38(1):e1-2. doi: 10.2337/dc14-1801. No abstract available. |
| 27208320 | Background | FLAT-SUGAR Trial Investigators. Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk. Diabetes Care. 2016 Jun;39(6):973-81. doi: 10.2337/dc15-2782. Epub 2016 Apr 19. |
| 27295427 | Background | Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22. doi: 10.1056/NEJMoa1603827. Epub 2016 Jun 13. |
| 31618560 | Background | Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ 3rd, Anderson SM, Church MM, Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW; iDCL Trial Research Group. Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes. N Engl J Med. 2019 Oct 31;381(18):1707-1717. doi: 10.1056/NEJMoa1907863. Epub 2019 Oct 16. |
| 21493665 | 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. |
| 31937608 | Background | Kovatchev B, Anderson SM, Raghinaru D, Kudva YC, Laffel LM, Levy C, Pinsker JE, Wadwa RP, Buckingham B, Doyle FJ 3rd, Brown SA, Church MM, Dadlani V, Dassau E, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Lum J, Beck RW; iDCL Study Group. Randomized Controlled Trial of Mobile Closed-Loop Control. Diabetes Care. 2020 Mar;43(3):607-615. doi: 10.2337/dc19-1310. Epub 2020 Jan 14. |
| 22851572 | Background | Miller RG, Secrest AM, Sharma RK, Songer TJ, Orchard TJ. Improvements in the life expectancy of type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications study cohort. Diabetes. 2012 Nov;61(11):2987-92. doi: 10.2337/db11-1625. Epub 2012 Jul 30. |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D013812 | Therapeutics |
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