Clinical trial NCT04492566: Automated Insulin Delivery in Pregnant Patients With Type 1 Diabetes With Extension Into Outpatient at Home
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Pregnancy
Keywords: type 1 diabetes
pregnancy
artificial pancreas
automated insulin delivery
Lead sponsor: Sansum Diabetes Research Institute
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
name: Harvard University
name: Icahn School of Medicine at Mount Sinai
First posted: 2020-07-30
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: Time in Target Glucose Range
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Secondary outcomes:
measure: Overnight Time in Target Glucose Range
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Postprandial Time in Target Glucose Range
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Glucose < 63 mg/dL
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Glucose < 54 mg/dL
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Glucose > 140 mg/dL
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Glucose > 180 mg/dL
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Hypoglycemic Events Per Week
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Severe Hypoglycemic Events
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Hyperglycemic Events
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Glucose > 250 mg/dL
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Serious Adverse Events (SAE)
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Serious Adverse Device Events (SADE)
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Adverse Device Effects (ADE)
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Unanticipated Adverse Device Effects (UADE)
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Mean CGM Glucose Level
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Other outcomes:
measure: Closed-Loop Active Time
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Sensor Use Time
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Maternal Outcomes: Gestational Hypertension
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Maternal Outcomes: Pre-eclampsia
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Maternal Outcomes: Eclampsia
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Maternal Outcomes: Oligo/Polyhydramnios
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Maternal Outcomes: Pre Term Labor
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Maternal Outcomes: Primary Caesarian Section
timeFrame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
measure: Fetal Outcomes: Large for Gestational Age
timeFrame: At Delivery
measure: Fetal Outcomes: Neonatal Hypoglycemia
timeFrame: At delivery and up to 48 hours afterwards
measure: Fetal Outcomes: Neonatal Intensive Care Unit Admission
timeFrame: At delivery and up to 7 days afterwards
Locations:
city: Santa Barbara
country: United States
facility: Sansum Diabetes Research Institute
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Harvard University John A Paulson School of Engineering and Applied Sciences
name: Eyal Dassau, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Yogish Kudva, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Carol Levy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Barak Rosenn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Grenye O'Malley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sansum Diabetes Research Institute
name: Kristin Castorino, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Sansum Diabetes Research Institute
name: Jordan Pinsker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.