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Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial.

ABSTRACT: The safety and efficacy of continuous, multiday, automated glycaemic management has not been tested in outpatient studies of preadolescent children with type 1 diabetes. We aimed to compare the safety and efficacy of a bihormonal bionic pancreas versus conventional insulin pump therapy in this population of patients in an outpatient setting.In this randomised, open-label, crossover study, we enrolled preadolescent children (aged 6-11 years) with type 1 diabetes (diagnosed for ?1 year) who were on insulin pump therapy, from two diabetes camps in the USA. With the use of sealed envelopes, participants were randomly assigned in blocks of two to either 5 days with the bionic pancreas or conventional insulin pump therapy (control) as the first intervention, followed by a 3 day washout period and then 5 days with the other intervention. Study allocation was not masked. The autonomously adaptive algorithm of the bionic pancreas received data from a continuous glucose monitoring (CGM) device to control subcutaneous delivery of insulin and glucagon. Conventional insulin pump therapy was administered by the camp physicians and other clinical staff in accordance with their established protocols; participants also wore a CGM device during the control period. The coprimary outcomes, analysed by intention to treat, were mean CGM-measured glucose concentration and the proportion of time with a CGM-measured glucose concentration below 3·3 mmol/L, on days 2-5. This study is registered with ClinicalTrials.gov, number NCT02105324.Between July 20, and Aug 19, 2014, 19 children with a mean age of 9·8 years (SD 1·6) participated in and completed the study. The bionic pancreas period was associated with a lower mean CGM-measured glucose concentration on days 2-5 than was the control period (7·6 mmol/L [SD 0·6] vs 9·3 mmol/L [1·7]; p=0·00037) and a lower proportion of time with a CGM-measured glucose concentration below 3·3 mmol/L on days 2-5 (1·2% [SD 1·1] vs 2·8% [1·2]; p<0·0001). The median number of carbohydrate interventions given per participant for hypoglycaemia on days 1-5 (ie, glucose <3·9 mmol/L) was lower during the bionic pancreas period than during the control period (three [range 0-8] vs five [0-14]; p=0·037). No episodes of severe hypoglycaemia were recorded. Medium-to-large concentrations of ketones (range 0·6-3·6 mmol/dL) were reported on seven occasions in five participants during the control period and on no occasion during the bionic pancreas period (p=0·063).The improved mean glycaemia and reduced hypoglycaemia with the bionic pancreas relative to insulin pump therapy in preadolescent children with type 1 diabetes in a diabetes camp setting is a promising finding. Studies of a longer duration during which children use the bionic pancreas during their normal routines at home and school should be done to investigate the potential for use of the bionic pancreas in real-world settings.The Leona M and Harry B Helmsley Charitable Trust and the US National Institute of Diabetes and Digestive and Kidney Diseases.

SUBMITTER: Russell SJ

PROVIDER: S-EPMC4799495 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial.

Russell Steven J SJ Hillard Mallory A MA Balliro Courtney C Magyar Kendra L KL Selagamsetty Rajendranath R Sinha Manasi M Grennan Kerry K Mondesir Debbie D Ekhlaspour Laya L Zheng Hui H Damiano Edward R ER El-Khatib Firas H FH

The lancet. Diabetes & endocrinology 20160203 3

<h4>Background</h4>The safety and efficacy of continuous, multiday, automated glycaemic management has not been tested in outpatient studies of preadolescent children with type 1 diabetes. We aimed to compare the safety and efficacy of a bihormonal bionic pancreas versus conventional insulin pump therapy in this population of patients in an outpatient setting.<h4>Methods</h4>In this randomised, open-label, crossover study, we enrolled preadolescent children (aged 6-11 years) with type 1 diabetes ...[more]

PMID: 26850709

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Project description:BackgroundTight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve glucose control while alleviating the risk of hypoglycaemia in adults with HbA1c below 7·5% (58 mmol/mol).MethodsIn this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2-4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2-4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9-10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed.FindingsBetween March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6-13·4; p<0·0001) during closed-loop delivery compared with usual pump therapy (65·6% [SD 8·1] when participants used usual pump therapy vs 76·2% [6·4] when they used closed-loop). Compared with usual pump therapy, closed-loop delivery also reduced the proportion of time spent in hypoglycaemia: the proportion of time with glucose concentration below 3·5 mmol/L was reduced by 65% (53-74, p<0·0001) and below 2·8 mmol/L by 76% (59-86, p<0·0001). No episodes of serious hypoglycaemia or other serious adverse events occurred.InterpretationUse of day-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies are warranted.FundingSwiss National Science Foundation (P1BEP3_165297), JDRF, UK National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z).

Project description:BackgroundThe safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity.MethodsWe did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant's body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2-11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220.FindingsWe randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7-1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8-1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0-10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21-0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study.InterpretationRelative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas.FundingNational Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.

Project description:OBJECTIVE:This study evaluated the feasibility, safety, and efficacy of day-and-night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes under free-living conditions. RESEARCH DESIGN AND METHODS:In an open-label randomized crossover study, 12 suboptimally controlled adolescents on insulin pump therapy (mean ± SD age 14.6 ± 3.1 years; HbA1c 69 ± 8 mmol/mol [8.5 ± 0.7%]; duration of diabetes 7.8 ± 3.5 years) underwent two 21-day periods in which hybrid closed-loop insulin delivery was compared with sensor-augmented insulin pump therapy in random order. During the closed-loop intervention, a model predictive algorithm automatically directed insulin delivery between meals and overnight. Participants used a bolus calculator to administer prandial boluses. RESULTS:The proportion of time that sensor glucose was in the target range (3.9-10 mmol/L; primary end point) was increased during the closed-loop intervention compared with sensor-augmented insulin pump therapy by 18.8 ± 9.8 percentage points (mean ± SD; P < 0.001), the mean sensor glucose level was reduced by 1.8 ± 1.3 mmol/L (P = 0.001), and the time spent above target was reduced by 19.3 ± 11.3 percentage points (P < 0.001). The time spent with sensor glucose levels below 3.9 mmol/L was low and comparable between interventions (median difference 0.4 [interquartile range -2.2 to 1.3] percentage points; P = 0.33). Improved glucose control during closed-loop was associated with increased variability of basal insulin delivery (P < 0.001) and an increase in the total daily insulin dose (53.5 [39.5-72.1] vs. 51.5 [37.6-64.3] units/day; P = 0.006). Participants expressed positive attitudes and experience with the closed-loop system. CONCLUSIONS:Free-living home use of day-and-night closed-loop in suboptimally controlled adolescents with type 1 diabetes is safe, feasible, and improves glucose control without increasing the risk of hypoglycemia. Larger and longer studies are warranted.

Project description:BackgroundThe safety and effectiveness of automated glycemic management have not been tested in multiday studies under unrestricted outpatient conditions.MethodsIn two random-order, crossover studies with similar but distinct designs, we compared glycemic control with a wearable, bihormonal, automated, "bionic" pancreas (bionic-pancreas period) with glycemic control with an insulin pump (control period) for 5 days in 20 adults and 32 adolescents with type 1 diabetes mellitus. The automatically adaptive algorithm of the bionic pancreas received data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon.ResultsAmong the adults, the mean plasma glucose level over the 5-day bionic-pancreas period was 138 mg per deciliter (7.7 mmol per liter), and the mean percentage of time with a low glucose level (<70 mg per deciliter [3.9 mmol per liter]) was 4.8%. After 1 day of automatic adaptation by the bionic pancreas, the mean (±SD) glucose level on continuous monitoring was lower than the mean level during the control period (133±13 vs. 159±30 mg per deciliter [7.4±0.7 vs. 8.8±1.7 mmol per liter], P<0.001) and the percentage of time with a low glucose reading was lower (4.1% vs. 7.3%, P=0.01). Among the adolescents, the mean plasma glucose level was also lower during the bionic-pancreas period than during the control period (138±18 vs. 157±27 mg per deciliter [7.7±1.0 vs. 8.7±1.5 mmol per liter], P=0.004), but the percentage of time with a low plasma glucose reading was similar during the two periods (6.1% and 7.6%, respectively; P=0.23). The mean frequency of interventions for hypoglycemia among the adolescents was lower during the bionic-pancreas period than during the control period (one per 1.6 days vs. one per 0.8 days, P<0.001).ConclusionsAs compared with an insulin pump, a wearable, automated, bihormonal, bionic pancreas improved mean glycemic levels, with less frequent hypoglycemic episodes, among both adults and adolescents with type 1 diabetes mellitus. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01762059 and NCT01833988.).

Project description:BackgroundCurrently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting.MethodsIn this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed.ResultsA total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group.ConclusionsIn this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).

Dataset Information

Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial.

Publications

Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial.

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