Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes

An open-label, multicentre, multinational, single-period, randomised, parallel group study protocol

Gianluca Musolino, Janet M. Allen, Sara Hartnell, Malgorzata E. Wilinska, Martin Tauschmann, Charlotte Boughton, Fiona Campbell, Louise Denvir, Nicola Trevelyan, Paul Wadwa, Linda DiMeglio, Bruce A. Buckingham, Stuart Weinzimer, Carlo L. Acerini, Korey Hood, Steven Fox, Craig Kollman, Judy Sibayan, Sarah Borgman, Peiyao Cheng & 1 others Roman Hovorka

Research output: Contribution to journalArticle

Abstract

Introduction Closed-loop systems titrate insulin based on sensor glucose levels, providing novel means to reduce the risk of hypoglycaemia while improving glycaemic control. We will assess effectiveness of 6-month day-and-night closed-loop insulin delivery compared with usual care (conventional or sensor-augmented pump therapy) in children and adolescents with type 1 diabetes. Methods and analysis The trial adopts an open-label, multicentre, multinational (UK and USA), randomised, single-period, parallel design. Participants (n=130) are children and adolescents (aged ≥6 and <19 years) with type 1 diabetes for at least 1 year, and insulin pump use for at least 3 months with suboptimal glycaemic control (glycated haemoglobin ≥58 mmol/mol (7.5%) and ≤86 mmol/mol (10%)). After a 2-3 week run-in period, participants will be randomised to 6-month use of hybrid closed-loop insulin delivery, or to usual care. Analyses will be conducted on an intention-to-treat basis. The primary outcome is glycated haemoglobin at 6 months. Other key endpoints include time in the target glucose range (3.9-10 mmol/L, 70-180 mg/dL), mean sensor glucose and time spent above and below target. Secondary outcomes include SD and coefficient of variation of sensor glucose levels, time with sensor glucose levels <3.5 mmol/L (63 mg/dL) and <3.0 mmol/L (54 mg/dL), area under the curve of glucose <3.5 mmol/L (63 mg/dL), time with glucose levels >16.7 mmol/L (300 mg/dL), area under the curve of glucose >10.0 mmol/L (180 mg/dL), total, basal and bolus insulin dose, body mass index z-score and blood pressure. Cognitive, emotional and behavioural characteristics of participants and caregivers and their responses to the closed-loop and clinical trial will be assessed. An incremental cost-effectiveness ratio for closed-loop will be estimated. Ethics and dissemination Cambridge South Research Ethics Committee and Jaeb Center for Health Research Institutional Review Office approved the study. The findings will be disseminated by peer-review publications and conference presentations. Trial registration number NCT02925299; Pre-results.

Original languageEnglish (US)
Article numbere027856
JournalBMJ Open
Volume9
Issue number6
DOIs
StatePublished - Jun 1 2019

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Social Conditions
Type 1 Diabetes Mellitus
Insulin
Safety
Glucose
Peer Review
Research Ethics Committees
Hypoglycemia
Ethics
Caregivers
Area Under Curve
Cost-Benefit Analysis
Publications
Body Mass Index
Therapeutics
Clinical Trials
Blood Pressure
Health
Research

Keywords

  • artificial pancreas
  • closed-loop
  • type 1 diabetes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes : An open-label, multicentre, multinational, single-period, randomised, parallel group study protocol. / Musolino, Gianluca; Allen, Janet M.; Hartnell, Sara; Wilinska, Malgorzata E.; Tauschmann, Martin; Boughton, Charlotte; Campbell, Fiona; Denvir, Louise; Trevelyan, Nicola; Wadwa, Paul; DiMeglio, Linda; Buckingham, Bruce A.; Weinzimer, Stuart; Acerini, Carlo L.; Hood, Korey; Fox, Steven; Kollman, Craig; Sibayan, Judy; Borgman, Sarah; Cheng, Peiyao; Hovorka, Roman.

In: BMJ Open, Vol. 9, No. 6, e027856, 01.06.2019.

Research output: Contribution to journalArticle

Musolino, G, Allen, JM, Hartnell, S, Wilinska, ME, Tauschmann, M, Boughton, C, Campbell, F, Denvir, L, Trevelyan, N, Wadwa, P, DiMeglio, L, Buckingham, BA, Weinzimer, S, Acerini, CL, Hood, K, Fox, S, Kollman, C, Sibayan, J, Borgman, S, Cheng, P & Hovorka, R 2019, 'Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes: An open-label, multicentre, multinational, single-period, randomised, parallel group study protocol', BMJ Open, vol. 9, no. 6, e027856. https://doi.org/10.1136/bmjopen-2018-027856
Musolino, Gianluca ; Allen, Janet M. ; Hartnell, Sara ; Wilinska, Malgorzata E. ; Tauschmann, Martin ; Boughton, Charlotte ; Campbell, Fiona ; Denvir, Louise ; Trevelyan, Nicola ; Wadwa, Paul ; DiMeglio, Linda ; Buckingham, Bruce A. ; Weinzimer, Stuart ; Acerini, Carlo L. ; Hood, Korey ; Fox, Steven ; Kollman, Craig ; Sibayan, Judy ; Borgman, Sarah ; Cheng, Peiyao ; Hovorka, Roman. / Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes : An open-label, multicentre, multinational, single-period, randomised, parallel group study protocol. In: BMJ Open. 2019 ; Vol. 9, No. 6.
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T1 - Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes

T2 - An open-label, multicentre, multinational, single-period, randomised, parallel group study protocol

AU - Musolino, Gianluca

AU - Allen, Janet M.

AU - Hartnell, Sara

AU - Wilinska, Malgorzata E.

AU - Tauschmann, Martin

AU - Boughton, Charlotte

AU - Campbell, Fiona

AU - Denvir, Louise

AU - Trevelyan, Nicola

AU - Wadwa, Paul

AU - DiMeglio, Linda

AU - Buckingham, Bruce A.

AU - Weinzimer, Stuart

AU - Acerini, Carlo L.

AU - Hood, Korey

AU - Fox, Steven

AU - Kollman, Craig

AU - Sibayan, Judy

AU - Borgman, Sarah

AU - Cheng, Peiyao

AU - Hovorka, Roman

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Introduction Closed-loop systems titrate insulin based on sensor glucose levels, providing novel means to reduce the risk of hypoglycaemia while improving glycaemic control. We will assess effectiveness of 6-month day-and-night closed-loop insulin delivery compared with usual care (conventional or sensor-augmented pump therapy) in children and adolescents with type 1 diabetes. Methods and analysis The trial adopts an open-label, multicentre, multinational (UK and USA), randomised, single-period, parallel design. Participants (n=130) are children and adolescents (aged ≥6 and <19 years) with type 1 diabetes for at least 1 year, and insulin pump use for at least 3 months with suboptimal glycaemic control (glycated haemoglobin ≥58 mmol/mol (7.5%) and ≤86 mmol/mol (10%)). After a 2-3 week run-in period, participants will be randomised to 6-month use of hybrid closed-loop insulin delivery, or to usual care. Analyses will be conducted on an intention-to-treat basis. The primary outcome is glycated haemoglobin at 6 months. Other key endpoints include time in the target glucose range (3.9-10 mmol/L, 70-180 mg/dL), mean sensor glucose and time spent above and below target. Secondary outcomes include SD and coefficient of variation of sensor glucose levels, time with sensor glucose levels <3.5 mmol/L (63 mg/dL) and <3.0 mmol/L (54 mg/dL), area under the curve of glucose <3.5 mmol/L (63 mg/dL), time with glucose levels >16.7 mmol/L (300 mg/dL), area under the curve of glucose >10.0 mmol/L (180 mg/dL), total, basal and bolus insulin dose, body mass index z-score and blood pressure. Cognitive, emotional and behavioural characteristics of participants and caregivers and their responses to the closed-loop and clinical trial will be assessed. An incremental cost-effectiveness ratio for closed-loop will be estimated. Ethics and dissemination Cambridge South Research Ethics Committee and Jaeb Center for Health Research Institutional Review Office approved the study. The findings will be disseminated by peer-review publications and conference presentations. Trial registration number NCT02925299; Pre-results.

AB - Introduction Closed-loop systems titrate insulin based on sensor glucose levels, providing novel means to reduce the risk of hypoglycaemia while improving glycaemic control. We will assess effectiveness of 6-month day-and-night closed-loop insulin delivery compared with usual care (conventional or sensor-augmented pump therapy) in children and adolescents with type 1 diabetes. Methods and analysis The trial adopts an open-label, multicentre, multinational (UK and USA), randomised, single-period, parallel design. Participants (n=130) are children and adolescents (aged ≥6 and <19 years) with type 1 diabetes for at least 1 year, and insulin pump use for at least 3 months with suboptimal glycaemic control (glycated haemoglobin ≥58 mmol/mol (7.5%) and ≤86 mmol/mol (10%)). After a 2-3 week run-in period, participants will be randomised to 6-month use of hybrid closed-loop insulin delivery, or to usual care. Analyses will be conducted on an intention-to-treat basis. The primary outcome is glycated haemoglobin at 6 months. Other key endpoints include time in the target glucose range (3.9-10 mmol/L, 70-180 mg/dL), mean sensor glucose and time spent above and below target. Secondary outcomes include SD and coefficient of variation of sensor glucose levels, time with sensor glucose levels <3.5 mmol/L (63 mg/dL) and <3.0 mmol/L (54 mg/dL), area under the curve of glucose <3.5 mmol/L (63 mg/dL), time with glucose levels >16.7 mmol/L (300 mg/dL), area under the curve of glucose >10.0 mmol/L (180 mg/dL), total, basal and bolus insulin dose, body mass index z-score and blood pressure. Cognitive, emotional and behavioural characteristics of participants and caregivers and their responses to the closed-loop and clinical trial will be assessed. An incremental cost-effectiveness ratio for closed-loop will be estimated. Ethics and dissemination Cambridge South Research Ethics Committee and Jaeb Center for Health Research Institutional Review Office approved the study. The findings will be disseminated by peer-review publications and conference presentations. Trial registration number NCT02925299; Pre-results.

KW - artificial pancreas

KW - closed-loop

KW - type 1 diabetes

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