Protocol for a prospective, multicenter, parallel-group, open-label randomized controlled trial comparing standard care with Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control: the CO-PILOT trial

Alisa Boucsein; Yongwen Zhou; Jillian J Haszard; Craig A Jefferies; Esko J Wiltshire; Sara E Styles; Hamish R Crocket; Barbara C Galland; Maheen Pasha; Goran Petrovski; Ryan G Paul; Martin I de Bock; Benjamin J Wheeler

doi:10.1007/s40200-024-01397-4

Protocol for a prospective, multicenter, parallel-group, open-label randomized controlled trial comparing standard care with Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control: the CO-PILOT trial

J Diabetes Metab Disord. 2024 Mar 7;23(1):1397-1407. doi: 10.1007/s40200-024-01397-4. eCollection 2024 Jun.

Authors

Alisa Boucsein¹, Yongwen Zhou^{1

2}, Jillian J Haszard³, Craig A Jefferies^{4

5}, Esko J Wiltshire^{6

7}, Sara E Styles⁸, Hamish R Crocket⁹, Barbara C Galland¹, Maheen Pasha¹⁰, Goran Petrovski¹⁰, Ryan G Paul^{9

11}, Martin I de Bock^{12

13}, Benjamin J Wheeler^{1

14}

Affiliations

¹ Department of Women's and Children's Health, University of Otago, Dunedin, New Zealand.
² Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China (USTC), 230001 Hefei, Anhui China.
³ Biostatistics Centre, University of Otago, Dunedin, New Zealand.
⁴ Starship Child Health, Te Whatu Ora Te Toka Tumai Auckland, Auckland, New Zealand.
⁵ Liggins Institute, Department of Paediatrics, The University of Auckland, Auckland, New Zealand.
⁶ Department of Paediatrics and Child Health, University of Otago Wellington, Wellington, New Zealand.
⁷ Te Whatu Ora Capital, Coast and Hutt Valley, Wellington, New Zealand.
⁸ Department of Human Nutrition, University of Otago, Dunedin, New Zealand.
⁹ Te Huatakia Waiora School of Health, University of Waikato, Hamilton, New Zealand.
¹⁰ Sidra Medicine, Doha, Qatar.
¹¹ Waikato Regional Diabetes Service, Te Whatu Ora Waikato, Hamilton, New Zealand.
¹² Department of Paediatrics, University of Otago, Christchurch, New Zealand.
¹³ Te Whatu Ora Waitaha Canterbury, Christchurch, New Zealand.
¹⁴ Te Whatu Ora Southern, Dunedin, New Zealand.

Abstract

Purpose: Advanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA_1c has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group.

Methods: A prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7-25 years with T1D, a current HbA_1c ≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA_1c between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes.

Conclusion: This study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden.

Trial registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452).

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-024-01397-4.

Keywords: Advanced hybrid closed loop; Artificial pancreas; Automated insulin delivery; Children and youth; Glycemic control; Type 1 diabetes.