Randomized Controlled Trial of Mobile Closed-Loop Control

Abstract

Assess the efficacy of inControl AP, a mobile closed-loop control (CLC) system. RESEARCH DESIGN AND METHODSThis protocol, NCT02985866, is a 3-month parallel-group, multicenter, randomized unblinded trial designed to compare mobile CLC with sensor-augmented pump (SAP) therapy. Eligibility criteria were type 1 diabetes for at least 1 year, use of insulin pumps for at least 6 months, age ‡14 years, and baseline HbA 1c <10.5% (91 mmol/mol). The study was designed to assess two coprimary outcomes: superiority of CLC over SAP in continuous glucose monitor (CGM)-measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L. RESULTSBetween November 2017 and May 2018, 127 participants were randomly assigned 1:1 to CLC (n 5 65) versus SAP (n 5 62); 125 participants completed the study. CGM time below 3.9 mmol/L was 5.0% at baseline and 2.4% during follow-up in the CLC group vs. 4.7% and 4.0%, respectively, in the SAP group (mean difference 21.7% [95% CI 22.4, 21.0]; P < 0.0001 for superiority). CGM time above 10 mmol/L was 40% at baseline and 34% during follow-up in the CLC group vs. 43% and 39%, respectively, in the SAP group (mean difference 23.0% [95% CI 26.1, 0.1]; P < 0.0001 for noninferiority). One severe hypoglycemic event occurred in the CLC group, which was unrelated to the study device. CONCLUSIONSIn meeting its coprimary end points, superiority of CLC over SAP in CGM-measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L, the study has demonstrated that mobile CLC is feasible and could offer certain usability advantages over embedded systems, provided the connectivity between system components is stable.People with type 1 diabetes face a life-long optimization problem: limiting their exposure to hyperglycemia while simultaneously avoiding hypoglycemia (1). Classic studies have shown that many complications from diabetes are predicted by average glycemia, typically assessed by hemoglobin A 1c (HbA 1c ), and can be reduced with intensive insulin therapy (2,3); however, the risk for hypoglycemia remains the primary barrier to optimal glycemic control (1). At present, closed-loop control (CLC), known as the artificial pancreas, offers the best solution to this optimization problem: day-and-night real-time fine-tuning of insulin delivery by an automated system.In the past few years, the volume of CLC clinical trials increased dramatically. In 2018, the National Library of Medicine included 132 publications in the CLC field, and in the first 6 weeks of 2019 alone, 25 new articles were published. Research results are

Sleep and diabetes‐specific psycho‐behavioral outcomes of a new automated insulin delivery system in young children with type 1 diabetes and their parents

“…At present, there are two commercially‐available AID systems in the US: the first system (Medtronic 670G, Medtronic, Ireland) was initially approved for ages 14 years and older and was subsequently lowered to ages 7 years 1 ; and the most recent system (Tandem Control‐IQ, Tandem Diabetes Care, San Diego CA) was also originally approved for use in 14 years of age or older 2 and later lowered to 6 years. Despite this growing availability, there are few clinical trials on the use and efficacy of these AID systems in younger children; this population is especially vulnerable to problems with glucose control such as increased glucose variability and episodes of severe hypoglycemia and therefore may benefit from AID technology 3‐7 …”

Comparison Between Closed-Loop Insulin Delivery System (the Artificial Pancreas) and Sensor-Augmented Pump Therapy: A Randomized-Controlled Crossover Trial

“…Several randomized trials tested dosing algorithms for automated insulin delivery systems, comparing its efficacy to sensor-augmented pump therapy, in outpatient unsupervised settings with no remote monitoring. [7][8][9][10][11][12]14 Here, we present a relatively short study over 12 days that assesses our dosing algorithm in outpatient unsupervised settings. The algorithm was a less aggressive version than our previous algorithm, [18][19][20] to emphasize safety in our first outpatient study.…”

“…The Cambridge algorithm was tested in several trials, [7][8][9] including in participants with suboptimal 8 and good glycemic control, 9 and consistently showed improvements in glucose control. The University of Virginia's algorithm was also tested in several clinical trials, [10][11][12] and showed improvements in glucose control, although the benefits were lower when the algorithm was embedded in a phone as opposed to a pump. 11,12 The Medtronic first-generation dosing algorithm was tested in several nonrandomized trials, 13 but their second-generation algorithm was recently tested in a 4-week randomized trial, 14 and also showed improvements in glucose control.…”

7. Diabetes Technology: Standards of Medical Care in Diabetes—2021

“…Multiple studies, using a variety of systems with varying algorithms, pump, and sensors, have been performed in adults and children (163)(164)(165)(166)(167)(168)(169)(170)(171)(172)(173). Evidence suggests such systems may reduce A1C levels and improve time in range (174)(175)(176)(177)(178). They may lower the risk of exerciserelated hypoglycemia (179) and may have psychosocial benefits (180)(181)(182)(183).…”