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

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

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).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes; Pregnancy
• Intervention / Treatment: Device: Automated Insulin Delivery

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Barbara, California, United States, 93105
      • Sansum Diabetes Research Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

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:

  1. A1C > 9%
  2. Abnormal liver or renal function (Transaminase >2 times the upper limit of normal, creatinine > 1.5 mg/dL)
  3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: AID Evaluation; 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; 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.; 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
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Closed-Loop Active Time	Percent time (hours/day) of closed-loop use during the clinical trial	Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Sensor Use Time	Percent Time CGM during the clinical trial	Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Maternal Outcomes: Gestational Hypertension	Number of subjects who develop gestational hypertension during pregnancy	Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Maternal Outcomes: Pre-eclampsia	Number of subjects who develop pre-eclampsia during pregnancy	Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Maternal Outcomes: Eclampsia	Number of subjects who develop eclampsia during pregnancy	Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Maternal Outcomes: Oligo/Polyhydramnios	Number of subjects who develop oligo/polyhydramnios during pregnancy	Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Maternal Outcomes: Pre Term Labor	Number of subjects who develop pre term labor during pregnancy	Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Maternal Outcomes: Primary Caesarian Section	Number of subjects who underwent primary caesarian section	Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Fetal Outcomes: Large for Gestational Age	Number of infants born large for gestational age	At Delivery
Fetal Outcomes: Neonatal Hypoglycemia	Number of infants who develop neonatal hypoglycemia. Neonatal hypoglycemia is defined as treatment requiring IV dextrose, treatment of the newborn with glucose gel is also reported, however protocols for use of glucose gel varied by delivery location.	At delivery and up to 48 hours afterwards
Fetal Outcomes: Neonatal Intensive Care Unit Admission	Number of infants who are admitted to the neonatal intensive care unit	At delivery and up to 7 days afterwards

Collaborators and Investigators

• Sponsor: Sansum Diabetes Research Institute
• Collaborators: Mayo Clinic; Icahn School of Medicine at Mount Sinai; Harvard University
• Investigators: Principal Investigator: Carol Levy, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Barak Rosenn, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Eyal Dassau, PhD, Harvard University John A Paulson School of Engineering and Applied Sciences; Principal Investigator: Yogish Kudva, MD, Mayo Clinic; Principal Investigator: Kristin Castorino, DO, Sansum Diabetes Research Institute; Principal Investigator: Grenye O'Malley, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Jordan Pinsker, MD, Sansum Diabetes Research Institute

Publications and helpful links

General Publications

• Levy CJ, Kudva YC, Ozaslan B, Castorino K, O'Malley G, Kaur RJ, Levister CM, Church MM, Desjardins D, McCrady-Spitzer S, Ogyaadu S, Trinidad MC, Reid C, Rizvi S, Deshpande S, Zaniletti I, Kremers WK, Pinsker JE, Doyle FJ, Dassau E; LOIS-P Diabetes and Pregnancy Consortium. At-Home Use of a Pregnancy-Specific Zone-MPC Closed-Loop System for Pregnancies Complicated by Type 1 Diabetes: A Single-Arm, Observational Multicenter Study. Diabetes Care. 2023 Jul 1;46(7):1425-1431. doi: 10.2337/dc23-0173.
• Ozaslan B, Levy CJ, Kudva YC, Pinsker JE, O'Malley G, Kaur RJ, Castorino K, Levister C, Trinidad MC, Desjardins D, Church MM, Plesser M, McCrady-Spitzer S, Ogyaadu S, Nelson K, Reid C, Deshpande S, Kremers WK, Doyle FJ , III, Rosenn B, Dassau E. Feasibility of Closed-Loop Insulin Delivery with a Pregnancy-Specific Zone Model Predictive Control Algorithm. Diabetes Technol Ther. 2022 Jul;24(7):471-480. doi: 10.1089/dia.2021.0521. Epub 2022 Apr 26.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2020
• Primary Completion (Actual): October 5, 2022
• Study Completion (Actual): October 5, 2022

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 30, 2020

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: pregnancy; artificial pancreas; type 1 diabetes; automated insulin delivery
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Gastrointestinal Agents; Pancrelipase
• Other Study ID Numbers: G200099/S001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No