Medical Food Assessment Using a Smartphone App With Continuous Glucose Monitoring Sensors: Proof-of-Concept Study
Hector Roux de Bézieux, James Bullard, Orville Kolterman, Michael Souza, Fanny Perraudeau, Hector Roux de Bézieux, James Bullard, Orville Kolterman, Michael Souza, Fanny Perraudeau
Abstract
Background: Novel wearable biosensors, ubiquitous smartphone ownership, and telemedicine are converging to enable new paradigms of clinical research. A new generation of continuous glucose monitoring (CGM) devices provides access to clinical-grade measurement of interstitial glucose levels. Adoption of these sensors has become widespread for the management of type 1 diabetes and is accelerating in type 2 diabetes. In parallel, individuals are adopting health-related smartphone-based apps to monitor and manage care.
Objective: We conducted a proof-of-concept study to investigate the potential of collecting robust, annotated, real-time clinical study measures of glucose levels without clinic visits.
Methods: Self-administered meal-tolerance tests were conducted to assess the impact of a proprietary synbiotic medical food on glucose control in a 6-week, double-blind, placebo-controlled, 2×2 cross-over pilot study (n=6). The primary endpoint was incremental glucose measured using Abbott Freestyle Libre CGM devices associated with a smartphone app that provided a visual diet log.
Results: All subjects completed the study and mastered CGM device usage. Over 40 days, 3000 data points on average per subject were collected across three sensors. No adverse events were recorded, and subjects reported general satisfaction with sensor management, the study product, and the smartphone app, with an average self-reported satisfaction score of 8.25/10. Despite a lack of sufficient power to achieve statistical significance, we demonstrated that we can detect meaningful changes in the postprandial glucose response in real-world settings, pointing to the merits of larger studies in the future.
Conclusions: We have shown that CGM devices can provide a comprehensive picture of glucose control without clinic visits. CGM device usage in conjunction with our custom smartphone app can lower the participation burden for subjects while reducing study costs, and allows for robust integration of multiple valuable data types with glucose levels remotely.
Trial registration: ClinicalTrials.gov NCT04424888; https://ichgcp.net/clinical-trials-registry/NCT04424888.
Keywords: clinical trials; continuous glucose monitoring; diabetes; lifestyle modification; mobile app; telemedicine.
Conflict of interest statement
Conflicts of Interest: All authors are employees and stock/stock option shareholders of Pendulum Therapeutics, Inc (formerly known as “Whole Biome Inc”). OK owns stock in GlySens, Inc, has stock options in ViaCyte, Inc, and is a consultant to NuSirt BioPharma, Adocia, Circius, and NanoPrecision Medical.
©Hector Roux de Bézieux, James Bullard, Orville Kolterman, Michael Souza, Fanny Perraudeau. Originally published in JMIR Formative Research (http://formative.jmir.org), 04.03.2021.
Figures
References
- World Health Organization . Global Report on Diabetes. Geneva: World Health Organization; 2016.
- Centers for Disease Control and Prevention . National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services; 2020.
- van Dam RM, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Ann Intern Med. 2002 Feb 05;136(3):201–9. doi: 10.7326/0003-4819-136-3-200202050-00008.
- Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O'Keefe JH, Brand-Miller J. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr. 2005 Feb;81(2):341–54. doi: 10.1093/ajcn.81.2.341.
- Qi L, Cornelis MC, Zhang C, van Dam RM, Hu FB. Genetic predisposition, Western dietary pattern, and the risk of type 2 diabetes in men. Am J Clin Nutr. 2009 May;89(5):1453–8. doi: 10.3945/ajcn.2008.27249.
- Franz MJ, MacLeod J. Success of nutrition-therapy interventions in persons with type 2 diabetes: challenges and future directions. Diabetes Metab Syndr Obes. 2018;11:265–270. doi: 10.2147/DMSO.S141952. doi: 10.2147/DMSO.S141952.
- Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The Lancet. 2018 Feb 10;391(10120):541–551. doi: 10.1016/S0140-6736(17)33102-1.
- Crichton GE, Howe PR, Buckley JD, Coates AM, Murphy KJ, Bryan J. Long-term dietary intervention trials: critical issues and challenges. Trials. 2012 Jul 20;13(1):111. doi: 10.1186/1745-6215-13-111.
- Lewis JD, Albenberg L, Lee D, Kratz M, Gottlieb K, Reinisch W. The Importance and Challenges of Dietary Intervention Trials for Inflammatory Bowel Disease. Inflamm Bowel Dis. 2017 Feb;23(2):181–191. doi: 10.1097/MIB.0000000000001009.
- Coran P, Goldsack JC, Grandinetti CA, Bakker JP, Bolognese M, Dorsey ER, Vasisht K, Amdur A, Dell C, Helfgott J, Kirchoff M, Miller CJ, Narayan A, Patel D, Peterson B, Ramirez E, Schiller D, Switzer T, Wing L, Forrest A, Doherty A. Advancing the Use of Mobile Technologies in Clinical Trials: Recommendations from the Clinical Trials Transformation Initiative. Digit Biomark. 2019;3(3):145–154. doi: 10.1159/000503957.
- Waltz E. Sweet sensation. Nat Biotechnol. 2019 Apr;37(4):340–344. doi: 10.1038/s41587-019-0086-2.
- Hirsch IB. Role of Continuous Glucose Monitoring in Diabetes Treatment. Arlington, VA: American Diabetes Association; 2018. History of Glucose Monitoring.
- Freestyle Libre 14 Day Flash Glucose Monitoring System. US Food & Drugs Administration. 2017. [2020-03-12]. .
- Declarations of Conformity. Abbott. [2020-03-25]. .
- Murata T, Sakane N, Kato K, Tone A, Toyoda M. The Current Intermittent-Scanning CGM Device Situation in Japan: Only Adjunctive Use to SMBG Is Approved and the Latest Health Insurance Coverage Details. J Diabetes Sci Technol. 2018 May;12(3):729–730. doi: 10.1177/1932296817749860.
- Bergenstal RM, Rosenstock J, Bastyr EJ, Prince MJ, Qu Y, Jacober SJ. Lower glucose variability and hypoglycemia measured by continuous glucose monitoring with novel long-acting insulin LY2605541 versus insulin glargine. Diabetes Care. 2014;37(3):659–65. doi: 10.2337/dc12-2621.
- Koyanagawa N, Miyoshi H, Ono K, Nakamura A, Cho KY, Yamamoto K, Takano Y, Dan-Noura M, Atsumi T. Comparative effects of vildagliptin and sitagliptin determined by continuous glucose monitoring in patients with type 2 diabetes mellitus. Endocr J. 2016 Aug 31;63(8):747–53. doi: 10.1507/endocrj.EJ16-0266. doi: 10.1507/endocrj.EJ16-0266.
- Jiménez-Domínguez G, Ble-Castillo JL, Aparicio-Trápala MA, Juárez-Rojop IE, Tovilla-Zárate CA, Ble-Castillo DJ, García-Vázquez C, Olvera-Hernández V, Pérez-Pimienta B, Diaz-Zagoya JC, Mendez JD. Effects of Acute Ingestion of Native Banana Starch on Glycemic Response Evaluated by Continuous Glucose Monitoring in Obese and Lean Subjects. Int J Environ Res Public Health. 2015 Jul 06;12(7):7491–505. doi: 10.3390/ijerph120707491.
- Nishimura R, Osonoi T, Kanada S, Jinnouchi H, Sugio K, Omiya H, Ubukata M, Sakai S, Samukawa Y. Effects of luseogliflozin, a sodium-glucose co-transporter 2 inhibitor, on 24-h glucose variability assessed by continuous glucose monitoring in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, crossover study. Diabetes Obes Metab. 2015 Aug;17(8):800–4. doi: 10.1111/dom.12481.
- Jinnouchi H, Koyama M, Amano A, Takahashi Y, Yoshida A, Hieshima K, Sugiyama S, Kurinami N, Jinnouchi T, Becker R. Continuous Glucose Monitoring During Basal-Bolus Therapy Using Insulin Glargine 300 U mL(-1) and Glargine 100 U mL (-1) in Japanese People with Type 1 Diabetes Mellitus: A Crossover Pilot Study. Diabetes Ther. 2015 Jun;6(2):143–52. doi: 10.1007/s13300-015-0115-1.
- Holst JJ, Buse JB, Rodbard HW, Linjawi S, Woo VC, Boesgaard TW, Kvist K, Gough SC. IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test. J Diabetes Sci Technol. 2015 Oct 06;10(2):389–97. doi: 10.1177/1932296815610124.
- Danne T, Philotheou A, Goldman D, Guo X, Ping L, Cali A, Johnston P. A randomized trial comparing the rate of hypoglycemia--assessed using continuous glucose monitoring--in 125 preschool children with type 1 diabetes treated with insulin glargine or NPH insulin (the PRESCHOOL study) Pediatr Diabetes. 2013 Dec;14(8):593–601. doi: 10.1111/pedi.12051. doi: 10.1111/pedi.12051.
- Study Demonstrates Remote CGM Initiation Successful at Improving Diabetes Outcomes and Quality of Life. PRWeb. [2020-02-17]. .
- Aberer F, Lichtenegger KM, Smajic E, Donsa K, Malle O, Samonigg J, Höll B, Beck P, Pieber TR, Plank J, Mader JK. GlucoTab-guided insulin therapy using insulin glargine U300 enables glycaemic control with low risk of hypoglycaemia in hospitalized patients with type 2 diabetes. Diabetes Obes Metab. 2019 Mar;21(3):584–591. doi: 10.1111/dom.13559.
- Reddy R, El Youssef J, Winters-Stone K, Branigan D, Leitschuh J, Castle J, Jacobs PG. The effect of exercise on sleep in adults with type 1 diabetes. Diabetes Obes Metab. 2018 Feb;20(2):443–447. doi: 10.1111/dom.13065.
- Perraudeau F, McMurdie P, Bullard J, Cheng A, Cutcliffe C, Deo A, Eid J, Gines J, Iyer M, Justice N, Loo WT, Nemchek M, Schicklberger M, Souza M, Stoneburner B, Tyagi S, Kolterman O. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res Care. 2020 Jul;8(1) doi: 10.1136/bmjdrc-2020-001319.
- Girish P. Simple Algorithms for Peak Detection in Time-Series. ResearchGate. 2009. [2019-05-12]. .
- BOOST® Original. Nestlé Health Science. [2019-11-20]. .
- Potteiger J, Jacobsen D, Donnelly J. A comparison of methods for analyzing glucose and insulin areas under the curve following nine months of exercise in overweight adults. Int J Obes Relat Metab Disord. 2002 Jan 15;26(1):87–9. doi: 10.1038/sj.ijo.0801839.
- Schnell O, Barnard K, Bergenstal R, Bosi E, Garg S, Guerci B, Haak T, Hirsch IB, Ji L, Joshi SR, Kamp M, Laffel L, Mathieu C, Polonsky WH, Snoek F, Home P. Role of Continuous Glucose Monitoring in Clinical Trials: Recommendations on Reporting. Diabetes Technol Ther. 2017 Jul;19(7):391–399. doi: 10.1089/dia.2017.0054.
- Schmidt MI, Hadji-Georgopoulos A, Rendell M, Margolis S, Kowarski A. The dawn phenomenon, an early morning glucose rise: implications for diabetic intraday blood glucose variation. Diabetes Care. 1981;4(6):579–85. doi: 10.2337/diacare.4.6.579.
- Two-Hour Postprandial Glucose. University of Rochester Medical Center. [2021-02-20]. .
- GitHub. [2021-02-15]. .
- Thompson F, Subar A. Nutrition in the Prevention and Treatment of Disease. Bethesda, MD: Elsevier; 2001. Dietary Assessment Methodology; pp. 3–30.
- Fallaize R, Zenun Franco R, Pasang J, Hwang F, Lovegrove JA. Popular Nutrition-Related Mobile Apps: An Agreement Assessment Against a UK Reference Method. JMIR Mhealth Uhealth. 2019 Feb 20;7(2):e9838. doi: 10.2196/mhealth.9838.
- Ferrara G, Kim J, Lin S, Hua J, Seto E. A Focused Review of Smartphone Diet-Tracking Apps: Usability, Functionality, Coherence With Behavior Change Theory, and Comparative Validity of Nutrient Intake and Energy Estimates. JMIR Mhealth Uhealth. 2019 May 17;7(5):e9232. doi: 10.2196/mhealth.9232.
- Rhyner D, Loher H, Dehais J, Anthimopoulos M, Shevchik S, Botwey RH, Duke D, Stettler C, Diem P, Mougiakakou S. Carbohydrate Estimation by a Mobile Phone-Based System Versus Self-Estimations of Individuals With Type 1 Diabetes Mellitus: A Comparative Study. J Med Internet Res. 2016 May 11;18(5):e101. doi: 10.2196/jmir.5567.
- Spilker B. Methods of Assessing and Improving Patient Compliance in Clinical Trials. IRB: Ethics and Human Research. 1992 May;14(3):1. doi: 10.2307/3563718.
- Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001 Aug;23(8):1296–310. doi: 10.1016/s0149-2918(01)80109-0.
- Haas K, Hayoz S, Maurer-Wiesner S. Effectiveness and Feasibility of a Remote Lifestyle Intervention by Dietitians for Overweight and Obese Adults: Pilot Study. JMIR Mhealth Uhealth. 2019 Apr 11;7(4):e12289. doi: 10.2196/12289.
- Anguera JA, Jordan JT, Castaneda D, Gazzaley A, Areán PA. Conducting a fully mobile and randomised clinical trial for depression: access, engagement and expense. BMJ Innov. 2016 Jan;2(1):14–21. doi: 10.1136/bmjinnov-2015-000098.
- Wahle F, Kowatsch T, Fleisch E, Rufer M, Weidt S. Mobile Sensing and Support for People With Depression: A Pilot Trial in the Wild. JMIR Mhealth Uhealth. 2016 Sep 21;4(3):e111. doi: 10.2196/mhealth.5960.
- Dunn TC, Xu Y, Hayter G, Ajjan RA. Real-world flash glucose monitoring patterns and associations between self-monitoring frequency and glycaemic measures: A European analysis of over 60 million glucose tests. Diabetes Res Clin Pract. 2018 Mar;137:37–46. doi: 10.1016/j.diabres.2017.12.015.
Source: PubMed