TY - JOUR
T1 - Closed-loop insulin delivery in pregnant women with type 1 diabetes (CRISTAL)
T2 - a multicentre randomized controlled trial - study protocol
AU - Beunen, Kaat
AU - van Wilder, Nancy
AU - Ballaux, Dominique
AU - Vanhaverbeke, Gerd
AU - Taes, Youri
AU - Aers, Xavier-Philippe
AU - Nobels, Frank
AU - Marlier, Joke
AU - Lee, Dahae
AU - Cuypers, Joke
AU - Preumont, Vanessa
AU - Siegelaar, Sarah E.
AU - Painter, Rebecca C.
AU - Laenen, Annouschka
AU - Gillard, Pieter
AU - Mathieu, Chantal
AU - Benhalima, Katrien
N1 - Funding Information: This investigator-initiated study received a research grant from the Diabetes Liga Research Fund (grant number 2020-J1191940-218926), a collaboration between the Diabetes Liga and the King Baudouin Foundation. Medtronic provided the study devices and an unrestricted grant for academic research. K Benhalima and P Gillard are the recipient of a senior clinical research fellowship from FWO (the Flemish Research Council). K Beunen is the recipient of a PhD fellowship strategic basic research (FWO-SB) from FWO. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of this protocol manuscript for publication. Funding Information: K Benhalima is the recipient of a senior clinical research fellowship from FWO, the Flemish Research Council. K Beunen is the recipient of a PhD fellowship strategic basic research (FWO-SB) from FWO. Publisher Copyright: © 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Artificial pancreas
KW - Automated insulin delivery
KW - Closed-loop insulin delivery
KW - Pregnancy
KW - Type 1 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=85150315621&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s12884-023-05481-0
DO - https://doi.org/10.1186/s12884-023-05481-0
M3 - Article
C2 - 36927458
SN - 1471-2393
VL - 23
SP - 180
JO - BMC pregnancy and childbirth
JF - BMC pregnancy and childbirth
IS - 1
M1 - 180
ER -