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

• ClinicalTrials.gov Identifier: NCT04492566
• Recruitment Status: Recruiting
• First Posted: July 30, 2020
• Last Update Posted: June 22, 2021
• Sponsor: Sansum Diabetes Research Institute
• Collaborators: Mayo Clinic; Harvard University; Icahn School of Medicine at Mount Sinai
• Information provided by (Responsible Party): Sansum Diabetes Research Institute

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes; Pregnancy	Device: Automated Insulin Delivery	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 27, 2020
• Estimated Primary Completion Date: May 15, 2022
• Estimated Study Completion Date: May 31, 2022

Arms and Interventions

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 Name: Interoperable Artificial Pancreas System (iAPS)

Outcome Measures

Primary Outcome Measures :

1. Time in target glucose range [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Time in target glucose range 63-140 mg/dL measured by CGM to determine safety and efficacy of the integrated system

Secondary Outcome Measures :

1. Overnight time in target glucose range [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Sensor glucose time within the target range of 63-140 mg/dl overnight
2. Postprandial time in target glucose range [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Sensor glucose time within the target range of 63-140 mg/dl postprandially within 2 hours following mealsand 2 hours following meals
3. Glucose < 63 mg/dL [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Percent time GGM glucose < 63 mg/dL
4. Glucose < 54 mg/dL [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Percent time GGM glucose < 54 mg/dL
5. Glucose > 140 mg/dL [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Percent time GGM glucose > 140 mg/dL
6. Glucose > 180 mg/dL [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Percent time GGM glucose > 180 mg/dL
7. Hypoglycemic Events [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Number of hypoglycemic events, defined as time <54 mg/dL for 15 consecutive minutes followed by time >70 mg/dL for 15 consecutive minutes.
8. Severe Hypoglycemic Events [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Number of hypoglycemic events that events that require active assistance of another individual
9. Hyperglycemic Events [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Number of episodes with ketones >1 mmol/L
10. Glucose > 250 mg/dL [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
    Percent time GGM glucose > 250 mg/dL
11. Serious adverse events (SAE) [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
    The total number of serious adverse events during the clinical trial
12. Serious adverse device events (SADE) [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
    The total number of serious adverse events related to the study device use during the clinical trial
13. Adverse device effects (ADE) [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
    The total number of adverse device effects (ADE) during the clinical trial
14. Unanticipated adverse device effects (UADE) [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
    The total number of unanticipated adverse device effects (UADE) during the clinical trial
15. Mean CGM glucose level [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
    Mean CGM glucose level during AID use
16. Number of hypoglycemia treatments [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
    Number of hypoglycemia treatments given during AID use

Other Outcome Measures:

1. Closed-Loop Active Time [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Percent time (hours/day) of closed-loop use during the clinical trial
2. Sensor Use Time [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Total hours of CGM sensor use time during the clinical trial
3. Device Issues [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Total number of devices issues during the clinical trial
4. Total daily insulin use [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Total daily insulin use (units/day), compared week to week
5. Total basal insulin use [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Total daily basal insulin use (units/day) , compared week to week
6. Total bolus insulin use [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Total daily bolus insulin use (units/day), compared week to week
7. Maternal outcomes: gestational hypertension [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Number of subjects who develop gestational hypertension during pregnancy
8. Maternal outcomes: pre-eclampsia [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Number of subjects who develop pre-eclampsia during pregnancy
9. Maternal outcomes: eclampsia [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
   Number of subjects who develop eclampsia during pregnancy
10. Maternal outcomes: oligo/polyhydramnios [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
    Number of subjects who develop oligo/polyhydramnios during pregnancy
11. Maternal outcomes: pre term labor [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
    Number of subjects who develop pre term labor during pregnancy
12. Maternal outcomes: caesarian section [ Time Frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use ]
    Number of subjects who undergo caesarian section
13. Fetal Outcomes: Large for gestational age [ Time Frame: At Delivery ]
    Number of infants born large for gestational age
14. Fetal Outcomes: Neonatal hypoglycemia [ Time Frame: At delivery and up to 48 hours afterwards ]
    Number of infants who develop neonatal hypoglycemia
15. Fetal Outcomes: Neonatal intensive care unit admission [ Time Frame: At delivery and up to 7 days afterwards ]
    Number of infants who are admitted to the neonatal intensive care unit

Eligibility Criteria

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

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:

  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

Contacts and Locations

Contacts

Contact: Shelly McCrady-Spitzer; 507-255-0316; McCradySpitzer.Shelly@mayo.edu

Locations

United States, California

Sansum Diabetes Research Institute; Recruiting

Santa Barbara, California, United States, 93105

Contact: Kristin Castorino, N 805-682-7640 ext 256 kcastorino@sansum.org

Sub-Investigator: Kristin Castorino, DO

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Shelly McCrady-Spitzer 507-255-0316 McCradySpitzer.Shelly@mayo.edu

Principal Investigator: Yogish Kudva, MBBS

United States, New York

Icahn School of Medicine at Mount Sinai; Recruiting

New York, New York, United States, 10029

Contact: Camilla M Levister 212-241-5177 camilla.levister@mssm.edu

Principal Investigator: Carol Levy, MD

Sponsors and Collaborators

Sansum Diabetes Research Institute

Mayo Clinic

Harvard University

Icahn School of Medicine at Mount Sinai

Investigators

• 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: Carol Levy, MD; Icahn School of Medicine at Mount Sinai
• Principal Investigator: Barak Rosenn, MD; Icahn School of Medicine at Mount Sinai
• Principal Investigator: Grenye O'Malley, MD; Icahn School of Medicine at Mount Sinai
• Principal Investigator: Kristin Castorino, DO; Sansum Diabetes Research Institute
• Principal Investigator: Jordan Pinsker, MD; Sansum Diabetes Research Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 Apr 26. doi: 10.1089/dia.2021.0521. [Epub ahead of print]

• Responsible Party: Sansum Diabetes Research Institute
• ClinicalTrials.gov Identifier: NCT04492566
• Other Study ID Numbers: G200099/S001
• First Posted: July 30, 2020
• Last Update Posted: June 22, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Sansum Diabetes Research Institute:

type 1 diabetes; pregnancy; artificial pancreas; automated insulin delivery

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Pancrelipase; Gastrointestinal Agents