Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial. Issue 4 (April 2022)

• Record Type: Journal Article
• Authors: Ware, Julia; Boughton, Charlotte K; Allen, Janet M; Wilinska, Malgorzata E; Tauschmann, Martin; Denvir, Louise; Thankamony, Ajay; Campbell, Fiona M; Wadwa, R Paul; Buckingham, Bruce A; Davis, Nikki; DiMeglio, Linda A; Mauras, Nelly; Besser, Rachel E J; Ghatak, Atrayee; Weinzimer, Stuart A; Hood, Korey K; Fox, D Steven; Kanapka, Lauren; Kollman, Craig; Sibayan, Judy; Beck, Roy W; Hovorka, Roman; Hovorka, R; Acerini, C L; Thankamony, A; Allen, J M; Boughton, C K; Dovc, K; Dunger, D B; Ware, J; Musolino, G; Tauschmann, M; Wilinska, M E; Hayes, J F; Hartnell, S; Slegtenhorst, S; Ruan, Y; Haydock, M; Mangat, J; Denvir, L; Kanthagnany, SK; Law, J; Randell, T; Sachdev, P; Saxton, M; Coupe, A; Stafford, S; Ball, A; Keeton, R; Cresswell, R; Crate, L; Cripps, H; Fazackerley, H; Looby, L; Navarra, H; Saddington, C; Smith, V; Verhoeven, V; Bratt, S; Khan, N; Moyes, L; Sandhu, K; West, C; Wadwa, R P; Alonso, G; Forlenza, G; Slover, R; Towers, L; Berget, C; Coakley, A; Escobar, E; Jost, E; Lange, S; Messer, L; Thivener, K; Campbell, F M; Yong, J; Metcalfe, E; Allen, M; Ambler, S; Waheed, S; Exall, J; Tulip, J; Buckingham, B A; Ekhlaspour, L; Maahs, D; Norlander, L; Jacobson, T; Twon, M; Weir, C; Leverenz, B; Keller, J; Davis, N; Kumaran, A; Trevelyan, N; Dewar, H; Price, G; Crouch, G; Ensom, R; Haskell, L; Lueddeke, LM; Mauras, N; Benson, M; Bird, K; Englert, K; Permuy, J; Ponthieux, K; Marrero-Hernandez, J; DiMeglio, L A; Ismail, H; Jolivette, H; Sanchez, J; Woerner, S; Kirchner, M; Mullen, M; Tebbe, M; Besser, R EJ; Basu, S; London, R; Makaya, T; Ryan, F; Megson, C; Bowen-Morris, J; Haest, J; Law, R; Stamford, I; Ghatak, A; Deakin, M; Phelan, K; Thornborough, K; Shakeshaft, J; Weinzimer, S A; Cengiz, E; Sherr, J L; Van Name, M; Weyman, K; Carria, L; Steffen, A; Zgorski, M; Sibayan, J; Beck, R W; Borgman, S; Davis, J; Rusnak, J; Hellman, A; Cheng, P; Kanapka, L; Kollman, C; McCarthy, C; Chalasani, S; Hood, K K; Hanes, S; Viana, J; Lanning, M; Fox, D S; Arreaza-Rubin, G; Eggerman, T; Green, N; Janicek, R; Gabrielson, D; Belle, S H; Castle, J; Green, J; Legault, L; Willi, S M; Wysham, C;
• Is Part Of: Lancet. Volume 4:Issue 4(2022)
• Page Start: e245
• Page End: e255
• Publication Date: 2022-04
• Subjects: Medical care -- Data processing -- Periodicals; Medical care -- Information technology -- Periodicals; Medical informatics -- Periodicals; 610.285
• DOI: 10.1016/S2589-7500(22)00020-6
• Languages: English
• ISSNs: 2589-7500

Abstract

Summary: 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.