Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial

Summary

Background

Closed-loop systems link continuous glucose measurements to insulin delivery. We aimed to establish whether closed-loop insulin delivery could control overnight blood glucose in young people.

Methods

We undertook three randomised crossover studies in 19 patients aged 5–18 years with type 1 diabetes of duration 6·4 years (SD 4·0). We compared standard continuous subcutaneous insulin infusion and closed-loop delivery (n=13; APCam01); closed-loop delivery after rapidly and slowly absorbed meals (n=7; APCam02); and closed-loop delivery and standard treatment after exercise (n=10; APCam03). Allocation was by computer-generated random code. Participants were masked to plasma and sensor glucose. In APCam01, investigators were masked to plasma glucose. During closed-loop nights, glucose measurements were fed every 15 min into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. During control nights, patients' standard pump settings were applied. Primary outcomes were time for which plasma glucose concentration was 3·91–8·00 mmol/L or 3·90 mmol/L or lower. Analysis was per protocol. This trial is registered, number ISRCTN18155883.

Findings

17 patients were studied for 33 closed-loop and 21 continuous infusion nights. Primary outcomes did not differ significantly between treatment groups in APCam01 (12 analysed; target range, median 52% [IQR 43–83] closed loop vs 39% [15–51] standard treatment, p=0·06; ≤3·90 mmol/L, 1% [0–7] vs 2% [0–41], p=0·13), APCam02 (six analysed; target range, rapidly 53% [48–57] vs slowly absorbed meal 55% [37–64], p=0·97; ≤3·90 mmol/L, 0% [0–4] vs 0% [0–0], p=0·16]), and APCam03 (nine analysed; target range 78% [60–92] closed loop vs 43% [25–65] control, p=0·0245, not significant at corrected level; ≤3·90 mmol/L, 10% [2–15] vs 6% [0–44], p=0·27). A secondary analysis of pooled data documented increased time in the target range (60% [51–88] vs 40% [18–61]; p=0·0022) and reduced time for which glucose concentrations were 3·90 mmol/L or lower (2·1% (0·0–10·0) vs 4·1% (0·0–42·0); p=0·0304). No events with plasma glucose concentration lower than 3·0 mmol/L were recorded during closed-loop delivery, compared with nine events during standard treatment.

Interpretation

Closed-loop systems could reduce risk of nocturnal hypoglycaemia in children and adolescents with type 1 diabetes.

Funding

Juvenile Diabetes Research Foundation; European Foundation for Study of Diabetes; Medical Research Council Centre for Obesity and Related Metabolic Diseases; National Institute for Health Research Cambridge Biomedical Research Centre.