Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes

Not Applicable

Completed

• Conditions: Diabetes
• Interventions: Device: A standard insulin delivery system; Device: Automated closed-loop insulin delivery (AiD)

• Registration Number: NCT04938557
• Lead Sponsor: Norfolk and Norwich University Hospitals NHS Foundation Trust

Brief Summary

Evaluation of the biomedical and psychosocial impact of automated Closed-Loop (Artificial Pancreas) insulin delivery in women with type 1 diabetes during pregnancy

Detailed Description

An open-label, multi-centre, randomized, two-arm parallel group trial comparing automated closed-loop and standard insulin delivery.

124 pregnant women between 18 and 45 years of age with Type 1 Diabetes of at least 12 months' duration on standard insulin delivery (CSII or MDI) will be recruited through outpatient antenatal diabetes clinics. Women fulfilling the eligibility criteria will be randomized to automated insulin delivery (AiD) or to continue standard patient-directed insulin delivery (CSII or MDI) without AiD. The study will take place within the home and NHS antenatal clinical settings.

Additional blood samples for the research will be obtained at the 24th and 34th week of pregnancy and questionnaires will also be completed by the participant at the 34th week of pregnancy. Following this we will collect information on the birth.

25 of the woman randomised to the closed loop insulin delivery system will also be interviewed to gain more information on, among other things, their existing diabetes management practices, everyday work and family lives and their experience with the device.

Study Timeline

• Study Start: 2019-09-26
• Study First Submitted: 2021-05-18
• Study First Submitted QC: 2021-06-16
• Study First Posted: 2021-06-24
• Primary Completion: 2022-04-30
• Study Completion: 2023-06-30
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-15
• Last Update Posted: 2023-12-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 124

Inclusion Criteria

1. Between 18 and 45 years of age (inclusive).
2. A diagnosis of type 1 diabetes (T1D), as defined by WHO for at least 12 months.
3. A viable pregnancy confirmed by ultrasound, up to 13 weeks and 6 days gestation.
4. Currently on intensive insulin therapy (≥3 injections or CSII).
5. Willingness to use the study devices throughout the trial.
6. HbA1c level ≥48 mmol/mol (≥6.5%) at booking (first antenatal contact) and ≤86 mmol/mol (≤10%) at point of randomization.
7. Able to provide informed consent.
8. Have access to email.

Exclusion Criteria

1. Non-type 1 diabetes.
2. Any other physical or psychological disease which, in the opinion of the investigator, is likely to interfere with the normal conduct and interpretation of the study results e.g. untreated coeliac disease or untreated hypothyroidism.
3. Current treatment with drugs known to interfere with glucose metabolism as judged by the investigator such as high dose systemic corticosteroids, non-selective beta-blockers and MAO inhibitors.
4. Known or suspected allergy against insulin.
5. Women with advanced nephropathy (eGFR <45), severe autonomic neuropathy, uncontrolled gastroparesis or severe proliferative retinopathy, as judged by the investigator, that is likely to interfere with the normal conduct of the study and interpretation of study results.
6. Very good or very poor glycaemic control i.e. first antenatal HbA1c <48 mmol/mol (<6.5%) and current HbA1c >10% (>86 mmol/mol). Women who enter pregnancy with HbA1c >10% (>86 mmol/mol) may participate if they achieve HbA1c ≤10% (≤86 mmol/mol) before randomization.
7. Total daily insulin dose 1.5 IU/kg.
8. Severe visual or hearing impairment.
9. Unable to speak and understand English.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A Standard Insulin Delivery System	A standard insulin delivery system	This can include either: an insulin pump (Continuous Subcutaneous Insulin Infusion - CSII) or multiple daily injections (MDI) without closed-loop.
An Automated Closed-loop Insulin Delivery (AiD) System.	Automated closed-loop insulin delivery (AiD)	The intervention being evaluated in this trial is automated closed-loop insulin delivery (AiD). The closed-loop system comprises of three components: an insulin pump, a continuous glucose monitor (CGM) and a computer-based model predictive control (MPC) algorithm to compute information from the CGM into a recommended insulin dose.

Primary Outcome Measures

Name	Time	Method
The time spent with glucose levels between 3.5-7.8 mmol/L based on CGM measures (Time In Range TIR 3.5-7.8mmol/L)	Between 16 weeks gestation and delivery - an average of 18 weeks	The primary outcome is the percentage of time spent with glucose levels between 3.9-7.8 mmol/L based on CGM levels between 16 weeks gestation and delivery.as compared with standard self-directed insulin delivery in pregnant women with T1D.

Secondary Outcome Measures

Name	Time	Method
Gestational age at delivery	At >34 weeks (delivery)	The gestational age at delivery and indication for any preterm delivery (\<37 weeks). Measured in years.
Infant birth weight (LGA)	At >34 weeks (delivery)	Infant birth weight (customised birth weight percentile, incidence of large for gestational age (LGA).
CGM glucose index (Low)	Between 16 weeks gestation and delivery - an average of 18 weeks	The Low Blood Glucose Index (LBGI)
CGM glucose index (High)	Between 16 weeks gestation and delivery - an average of 18 weeks	High Blood Glucose Index (HBGI) measures
HbA1c testing (Maternal)	Blood samples will be collected at baseline, 24-26 weeks, 34-36 weeks	To assess the change of HbA1c in the maternal level.
The number and severity of episodes of adverse device effect.	<24 weeks gestation until delivery - an average of 16 weeks	Adverse events including pregnancy loss, stillbirth, neonatal death
Infant birth weight (SGA).	At >34 weeks (delivery)	Infant birth weight (customised birth weight percentile, incidence of small for gestational age (SGA).
CGM glucose measures	Between 16 weeks gestation and delivery - an average of 18 weeks	The time spent with CGM glucose levels above and below target range, using the mean CGM glucose and CGM glucose variability measures (CV, SD).
Diabetic ketoacidosis.	An average of 24 weeks	The frequency and severity of diabetic ketoacidosis
Severe hypoglycaemia episodes.	An average of 24 weeks	The frequency and severity of hypoglycaemia episodes defined as CGM glucose levels \<3.5 mmol/L (level 1 hypoglycaemia) and \<2.8 mmol/L (level 2 hypoglycaemia) for at least 15 minutes. Distinct episodes must be separated for at least 30 minutes.
Hospital length of stay (maternal).	Between 13 and 40 weeks - an average of 24 weeks	Hospital length of stay (all admissions including the delivery admission)
Mode of delivery	At >34 weeks (delivery)	How the infant is delivered, for example: vaginal, instrumental, elective caesarean section and emergency caesarean section)
Neonatal morbidity (hypoglycaemia, jaundice, respiratory distress).	Between delivery and 40 weeks - an average of 6 weeks	Neonatal morbidity including treatment for neonatal hypoglycaemia, neonatal jaundice and respiratory distress.
Neonatal intensive care unit (NICU) admission.	NICU admission after 24 hours	Neonatal intensive care unit (NICU) admission \>24 hours
Hospital length of stay (infant).	Between delivery and 40 weeks - an average of 6 weeks	Hospital length of stay for the infant

Trial Locations

Locations (1)

Norfolk and Norwich University Hospitals NHS Foundation Trust; 🇬🇧 Norwich, Norfolk, United Kingdom