TY - JOUR
T1 - Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes
T2 - a multicentre 6-month randomised controlled trial
AU - DAN05 Consortium
AU - Ware, Julia
AU - Boughton, Charlotte K.
AU - Allen, Janet M.
AU - Wilinska, Malgorzata E.
AU - Tauschmann, Martin
AU - Denvir, Louise
AU - Thankamony, Ajay
AU - Campbell, Fiona M.
AU - Wadwa, R. Paul
AU - Buckingham, Bruce A.
AU - Davis, Nikki
AU - DiMeglio, Linda A.
AU - Mauras, Nelly
AU - Besser, Rachel E.J.
AU - Ghatak, Atrayee
AU - Weinzimer, Stuart A.
AU - Hood, Korey K.
AU - Fox, D. Steven
AU - Kanapka, Lauren
AU - Kollman, Craig
AU - Sibayan, Judy
AU - Beck, Roy W.
AU - Hovorka, Roman
AU - Hovorka, R.
AU - Acerini, C. L.
AU - Thankamony, A.
AU - Allen, J. M.
AU - Boughton, C. K.
AU - Dovc, K.
AU - Dunger, D. B.
AU - Ware, J.
AU - Musolino, G.
AU - Tauschmann, M.
AU - Wilinska, M. E.
AU - Hayes, J. F.
AU - Hartnell, S.
AU - Slegtenhorst, S.
AU - Ruan, Y.
AU - Haydock, M.
AU - Mangat, J.
AU - Denvir, L.
AU - Kanthagnany, S. K.
AU - Law, J.
AU - Randell, T.
AU - Sachdev, P.
AU - Saxton, M.
AU - Coupe, A.
AU - Stafford, S.
AU - Ball, A.
AU - Castle, J.
N1 - Funding Information:
Acknowledgements, The study was funded by National Institutes of Diabetes, Digestive, and Kidney Diseases (UC4 DK108520). Additional support for the Artificial Pancreas work by National Institute for Health Research Cambridge Biomedical Research Centre and Wellcome Strategic Award (100574/Z/12/Z). Abbott Diabetes Care supplied continuous glucose monitoring devices and receivers. Dexcom provided support for the development of the CamAPS FX system and supplied discounted continuous glucose monitoring devices. Medtronic provided support for the development of the FlorenceM system and supplied discounted continuous glucose monitoring devices, phone enclosures, pumps and consumables. The views expressed are those of the author(s) and not necessarily those of the funders. We are grateful to study volunteers for their participation. We acknowledge support by the staff at the Addenbrooke's Wellcome Trust Clinical Research Facility.
Funding Information:
The study was funded by National Institutes of Diabetes, Digestive, and Kidney Diseases (UC4 DK108520). Additional support for the Artificial Pancreas work by National Institute for Health Research Cambridge Biomedical Research Centre and Wellcome Strategic Award (100574/Z/12/Z). Abbott Diabetes Care supplied continuous glucose monitoring devices and receivers. Dexcom provided support for the development of the CamAPS FX system and supplied discounted continuous glucose monitoring devices. Medtronic provided support for the development of the FlorenceM system and supplied discounted continuous glucose monitoring devices, phone enclosures, pumps and consumables. The views expressed are those of the author(s) and not necessarily those of the funders. We are grateful to study volunteers for their participation. We acknowledge support by the staff at the Addenbrooke's Wellcome Trust Clinical Research Facility.
Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2022/4
Y1 - 2022/4
N2 - Background: Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. Methods: In a multicentre, multinational, parallel randomised controlled trial, participants aged 6–18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0–10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. Findings: Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference −3·5 mmol/mol (95% CI −6·5 to −0·5 [–0·32 percentage points, −0·59 to −0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26–53]), but consistently high with CamAPS FX (93% [88–96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. Interpretation: The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. Funding: National Institute of Diabetes and Digestive and Kidney Diseases.
AB - Background: Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. Methods: In a multicentre, multinational, parallel randomised controlled trial, participants aged 6–18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0–10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. Findings: Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference −3·5 mmol/mol (95% CI −6·5 to −0·5 [–0·32 percentage points, −0·59 to −0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26–53]), but consistently high with CamAPS FX (93% [88–96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. Interpretation: The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. Funding: National Institute of Diabetes and Digestive and Kidney Diseases.
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U2 - 10.1016/S2589-7500(22)00020-6
DO - 10.1016/S2589-7500(22)00020-6
M3 - Article
C2 - 35272971
AN - SCOPUS:85126669881
SN - 2589-7500
VL - 4
SP - e245-e255
JO - The Lancet Digital Health
JF - The Lancet Digital Health
IS - 4
ER -