Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes

Conditions
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Diabetes

Intervention / Treatment
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* Device: Automated closed-loop insulin delivery (AiD)
* Device: A standard insulin delivery system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 18 and 45 years of age (inclusive). A diagnosis of type 1 diabetes (T1D), as defined by WHO for at least 12 months. A viable pregnancy confirmed by ultrasound, up to 13 weeks and 6 days gestation. Currently on intensive insulin therapy (≥3 injections or CSII). Willingness to use the study devices throughout the trial. HbA1c level ≥48 mmol/mol (≥6.5%) at booking (first antenatal contact) and ≤86 mmol/mol (≤10%) at point of randomization. Able to provide informed consent. Have access to email. Exclusion Criteria: Non-type 1 diabetes. 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. 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. Known or suspected allergy against insulin. 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. 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. Total daily insulin dose 1.5 IU/kg. Severe visual or hearing impairment. Unable to speak and understand English.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An open-label, multi-centre, randomized, two-arm parallel group trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: An Automated Closed-loop Insulin Delivery (AiD) System.<br>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. | Device: Automated closed-loop insulin delivery (AiD)<br>* Closed-loop systems are designed to deliver insulin in response to CGM glucose levels and may help to improve glucose control above and beyond what is currently achievable using insulin pumps, injections and CGM without AiD.<br>|
| Active Comparator: A Standard Insulin Delivery System<br>This can include either: an insulin pump (Continuous Subcutaneous Insulin Infusion - CSII) or multiple daily injections (MDI) without closed-loop. | Device: A standard insulin delivery system<br>* Self-directed insulin delivery for pregnant women with T1D, which is insulin pump or MDI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | Between 16 weeks gestation and delivery - an average of 18 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes