Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT)

• ClinicalTrials.gov Identifier: NCT04938557
• Recruitment Status: Completed
• First Posted: June 24, 2021
• Last Update Posted: December 18, 2023
• Sponsor: Norfolk and Norwich University Hospitals NHS Foundation Trust
• Collaborators: University of East Anglia; University of Cambridge; University of Leeds; University of Edinburgh; University of Glasgow; King's College London; Belfast Health and Social Care Trust
• Information provided by (Responsible Party): Norfolk and Norwich University Hospitals NHS Foundation Trust

Tracking Information

• First Submitted Date: May 18, 2021
• First Posted Date: June 24, 2021
• Last Update Posted Date: December 18, 2023
• Actual Study Start Date: September 26, 2019
• Actual Primary Completion Date: April 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 16, 2021)

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) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 16, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes
• Official Title: Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes
• 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 Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

An open-label, multi-centre, randomized, two-arm parallel group trial

Masking: None (Open Label)
Masking Description:

This is an unblinded trial. Both participants and their clinical care team will be aware of the allocation.

Primary Purpose: Treatment

• Condition: Diabetes

Intervention

• Device: Automated closed-loop insulin delivery (AiD)
  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.
• Device: A standard insulin delivery system
  Self-directed insulin delivery for pregnant women with T1D, which is insulin pump or MDI.

Study Arms

• Experimental: An Automated Closed-loop Insulin Delivery (AiD) System.
  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.
  Intervention: Device: Automated closed-loop insulin delivery (AiD)
• Active Comparator: 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.
  Intervention: Device: A standard insulin delivery system

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 16, 2021): 124
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 30, 2023
• Actual Primary Completion Date: April 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT04938557
• Other Study ID Numbers: 240380
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Norfolk and Norwich University Hospitals NHS Foundation Trust
• Original Responsible Party: Same as current
• Current Study Sponsor: Norfolk and Norwich University Hospitals NHS Foundation Trust
• Original Study Sponsor: Same as current

Collaborators

• University of East Anglia
• University of Cambridge
• University of Leeds
• University of Edinburgh
• University of Glasgow
• King's College London
• Belfast Health and Social Care Trust

Investigators

• Principal Investigator: Helen Murphy; University of East Anglia

• PRS Account: Norfolk and Norwich University Hospitals NHS Foundation Trust
• Verification Date: December 2023