闭环胰岛素输注在 1 型糖尿病孕妇中的应用（CRISTAL）：一项多中心随机对照试验 - 研究方案。
Closed-loop insulin delivery in pregnant women with type 1 diabetes (CRISTAL): a multicentre randomized controlled trial - study protocol.
机构信息
Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, Leuven, 3000, Belgium.
Department of Endocrinology, University Hospital Brussels, Laarbeeklaan 101, Jette, 1090, Belgium.
出版信息
BMC Pregnancy Childbirth. 2023 Mar 16;23(1):180. doi: 10.1186/s12884-023-05481-0.
BACKGROUND
Despite increasing use of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII, insulin pumps) in type 1 diabetes (T1D) in pregnancy, achieving recommended pregnancy glycaemic targets (3.5-7.8 mmol/L or 63-140 mg/dL) remains challenging. Consequently, the risk of adverse pregnancy outcomes remains high. Outside pregnancy, hybrid closed-loop (HCL) insulin delivery systems have led to a paradigm shift in the management of T1D, with 12% higher time in glucose target range (TIR) compared to conventional CSII. However, most commercially available HCL systems are currently not approved for use in pregnancy. This study aims to evaluate the efficacy, safety and cost-effectiveness of the MiniMed™ 780G HCL system (Medtronic) in T1D in pregnancy.
METHODS
In this international, open-label, randomized controlled trial (RCT), we will compare the MiniMed™ 780G HCL system to standard of care (SoC) in T1D in pregnancy. Women aged 18-45 years with T1D diagnosis of at least one year, HbA1c ≤ 86 mmol/mol (≤ 10%), and confirmed singleton pregnancy up to 11 weeks 6 days will be eligible. After providing written informed consent, all participants will wear a similar CGM system (Guardian™ 3 or Guardian™ 4 CGM) during a 10-day run-in phase. After the run-in phase, participants will be randomised 1:1 to 780G HCL (intervention) or SoC [control, continuation of current T1D treatment with multiple daily injections (MDI) or CSII and any type of CGM] stratified according to centre, baseline HbA1c (< 53 vs. ≥ 53 mmol/mol or < 7 vs. ≥ 7%), and method of insulin delivery (MDI or CSII). The primary outcome will be the time spent within the pregnancy glucose target range, as measured by the CGM at four time points in pregnancy: 14-17, 20-23, 26-29, and 33-36 weeks. Prespecified secondary outcomes will be overnight TIR, time below range (TBR: <3.5 mmol/L or < 63 mg/dL), and overnight TBR. Other outcomes will be exploratory. The planned sample size is 92 participants. The study will end after postpartum discharge from hospital. Analyses will be performed according to intention-to-treat as well as per protocol.
DISCUSSION
This large RCT will evaluate a widely used commercially available HCL system in T1D in pregnancy. Recruitment began in January 2021 and was completed in October 2022. Study completion is expected in May 2023.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT04520971. Registration date: August 20, 2020. https://clinicaltrials.gov/ct2/show/NCT04520971.
背景
尽管在妊娠期间 1 型糖尿病（T1D）中越来越多地使用连续血糖监测（CGM）和连续皮下胰岛素输注（CSII，胰岛素泵），但仍难以达到推荐的妊娠血糖目标（3.5-7.8 mmol/L 或 63-140 mg/dL）。因此，不良妊娠结局的风险仍然很高。在妊娠之外，混合闭环（HCL）胰岛素输送系统在 T1D 的管理方面带来了范式转变，与传统的 CSII 相比，葡萄糖目标范围内的时间（TIR）增加了 12%。然而，目前大多数市售的 HCL 系统尚未获准在妊娠期间使用。本研究旨在评估 MiniMed™ 780G HCL 系统（美敦力）在妊娠 T1D 中的疗效、安全性和成本效益。
方法
这是一项国际、开放标签、随机对照试验（RCT），我们将比较 MiniMed™ 780G HCL 系统与妊娠 T1D 的标准护理（SoC）。年龄在 18-45 岁之间、T1D 诊断至少一年、HbA1c≤86 mmol/mol（≤10%）且确诊为单胎妊娠至 11 周 6 天的女性将有资格参加。在书面知情同意后，所有参与者将在 10 天的运行期内佩戴类似的 CGM 系统（Guardian™ 3 或 Guardian™ 4 CGM）。运行期结束后，参与者将根据中心、基线 HbA1c（<53 与≥53 mmol/mol 或<7 与≥7%）和胰岛素输送方法（MDI 或 CSII）按 1:1 随机分为 780G HCL（干预组）或 SoC [对照组，继续使用 MDI 或 CSII 进行 T1D 治疗，以及任何类型的 CGM]。主要结局将是妊娠期间通过 CGM 在四个时间点测量的处于妊娠血糖目标范围内的时间：14-17、20-23、26-29 和 33-36 周。预设的次要结局将是夜间 TIR、低于目标范围的时间（TBR：<3.5 mmol/L 或 <63 mg/dL）和夜间 TBR。其他结局将是探索性的。计划样本量为 92 名参与者。研究将在产后出院后结束。分析将根据意向治疗和方案进行。
讨论
这项大型 RCT 将评估在妊娠 T1D 中广泛使用的一种市售 HCL 系统。招募于 2021 年 1 月开始，于 2022 年 10 月完成。预计于 2023 年 5 月完成研究。
试验注册
ClinicalTrials.gov：NCT04520971。注册日期：2020 年 8 月 20 日。https://clinicaltrials.gov/ct2/show/NCT04520971。
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