Automated Insulin Delivery in Pregnant Patients With Type 1 Diabetes With Extension Into Outpatient at Home

Study Overview
=================
Brief Summary
-----------------
This clinical trial is a safety and feasibility study to assess the performance of an artificial pancreas (AP) system using the Zone Model Predictive control (Zone-MPC) and Health Monitoring System (HMS) algorithms embedded into the iAPS platform for pregnant patients with type 1 diabetes (T1D).

Detailed Description
-----------------
The system will be evaluated on up to 21 pregnant adult subjects with type 1 diabetes age 18-45 years old at three clinical sites (Sansum Diabetes Research Institute, Mayo Clinic Rochester MN and Mt Sinai Hospital, New York City). Subjects will complete a 48-60 hour closed-loop (CL) session in a supervised outpatient environment with medical staff present. During the session, subjects will bolus for all meals and snacks, and will perform their usual daily activities while being accompanied by study medical staff. For subjects who wish to continue use of the system, they will be offered the option of continuing use of the system at home in an extension phase, for the rest of their pregnancy.

Official Title
-----------------
Supervised Safety and Feasibility Evaluation of the Zone-MPC Control Algorithm Integrated Into the iAPS in Pregnant Patients With Type 1 Diabetes With Extension Into Outpatient at Home

Conditions
-----------------
Type 1 Diabetes, Pregnancy

Intervention / Treatment
-----------------
* Device: Automated Insulin Delivery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 and ≤ 45 years at the time of screening. Clinical diagnosis of type 1 diabetes Currently using an insulin pump at the time of screening. HbA1c ≤ 9%, as performed by point of care or central laboratory testing. Pregnant 14+0/7 to 32+6/7 weeks gestation. Singleton pregnancy without any other significant known complications, such as preeclampsia, premature rupture of membranes, 2nd/3rd trimester bleeding, fetal growth or fluid abnormalities. No proven or suspected fetal malformations diagnosed in the current pregnancy. Bolus for all meals and snacks that contain ≥ 5 grams of carbohydrate. Willing to switch to, or continue Novolog or Humalog for the closed-loop session. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial. Willing to abide by the study protocol and use study-provided devices. Have a care partner with the following responsibilities: knowing subject whereabouts and being promptly available for contact by study staff during the day and night, residing in the same dwelling as subject during the night, being agreeable to all device training during the supervised HCL session and additional training on hyper- and hypoglycemia treatment, and assisting with emergency care if needed, such as transportation to the hospital or emergency department. Exclusion Criteria: Known unstable cardiac disease or untreated cardiac disease, as revealed by history or physical examination. Concurrent use of Afrezza or any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, Pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas). Hemophilia or any other bleeding disorder Prior history of Preterm Premature Rupture of Membranes (PPROM) Significant hyperemesis interfering with carbohydrate intake Laboratory results: A1C > 9% Abnormal liver or renal function (Transaminase >2 times the upper limit of normal, creatinine > 1.5 mg/dL) Liver and renal function testing drawn at screening visit or within three months prior to screening (for other purposes) will suffice for enrollment purposes Dermatological conditions that would preclude wearing a CGM sensor or infusion site. Any condition that could interfere with participating in the trial, based on investigator judgment. Participation in another pharmaceutical or device trial at the time of enrollment or during the study. Having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial History of severe hypoglycemia in the past 6 months History of DKA requiring hospitalization in the past 6 months Significant chronic kidney disease (eGFR < 60) or hemodialysis Significant liver disease History of adrenal insufficiency History of abnormal TSH consistent with hypothyroidism or hyperthyroidism that is not appropriately treated History of high dose steroid use in the past 8 weeks

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

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AID Evaluation<br>After completing a 1-2 week CGM run-in period, subjects will complete a 48-60 hour closed-loop (CL) session in a supervised outpatient environment with medical staff present. For subjects who wish to continue use of the system, they will be offered the option of continuing use of the system at home in an extension phase, for the rest of their pregnancy. | Device: Automated Insulin Delivery<br>* Participants will use the Automated Insulin Delivery (AID) iAPS system for 48-60 hours in a medically supervised session. For subjects who wish to continue use of the system, they will be offered the option of continuing use of the system at home in an extension phase, for the rest of their pregnancy.<br>* Other names: Interoperable Artificial Pancreas System (iAPS);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in Target Glucose Range | Time in target glucose range 63-140 mg/dL measured by CGM to determine safety and efficacy of the integrated system | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overnight Time in Target Glucose Range | Sensor glucose time within the target range of 63-140 mg/dl overnight | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Postprandial Time in Target Glucose Range | Sensor glucose time within the target range of 63-140 mg/dl postprandially within 2 hours following meals and 2 hours following meals | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Glucose < 63 mg/dL | Percent time CGM glucose < 63 mg/dL | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Glucose < 54 mg/dL | Percent time CGM glucose < 54 mg/dL | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Glucose > 140 mg/dL | Percent time GGM glucose > 140 mg/dL | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Glucose > 180 mg/dL | Percent time GGM glucose > 180 mg/dL | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Hypoglycemic Events Per Week | Number of hypoglycemic events per week, defined as time <54 mg/dL for 15 consecutive minutes followed by time >70 mg/dL for 15 consecutive minutes. | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Severe Hypoglycemic Events | Number of hypoglycemic events that events that require active assistance of another individual | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Hyperglycemic Events | Number of episodes with ketones >1 mmol/L | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Glucose > 250 mg/dL | Percent time GGM glucose > 250 mg/dL | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Serious Adverse Events (SAE) | The total number of serious adverse events during the clinical trial | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Serious Adverse Device Events (SADE) | The total number of serious adverse events related to the study device use during the clinical trial | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Adverse Device Effects (ADE) | The total number of adverse device effects (ADE) during the clinical trial | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Unanticipated Adverse Device Effects (UADE) | The total number of unanticipated adverse device effects (UADE) during the clinical trial | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 
| Mean CGM Glucose Level | Mean CGM glucose level during AID use | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
type 1 diabetes, pregnancy, artificial pancreas, automated insulin delivery