Pregnancy, Type 1 Diabetes
Conditions
Keywords
type 1 diabetes, pregnancy, artificial pancreas, automated insulin delivery
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.
Interventions
DEVICEAutomated 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.
Sponsors
Mayo Clinic
Harvard University
Icahn School of Medicine at Mount Sinai
Sansum Diabetes Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time in Target Glucose Range | 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
| Measure | Time frame | Description |
|---|---|---|
| Glucose < 63 mg/dL | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Percent time CGM glucose \< 63 mg/dL |
| Glucose > 140 mg/dL | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Percent time GGM glucose \> 140 mg/dL |
| Glucose > 180 mg/dL | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Percent time GGM glucose \> 180 mg/dL |
| Hypoglycemic Events Per Week | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | 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. |
| Severe Hypoglycemic Events | 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 |
| Hyperglycemic Events | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Number of episodes with ketones \>1 mmol/L |
| Glucose > 250 mg/dL | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Percent time GGM glucose \> 250 mg/dL |
| Serious Adverse Events (SAE) | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | The total number of serious adverse events during the clinical trial |
| Serious Adverse Device Events (SADE) | 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 |
| Adverse Device Effects (ADE) | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | The total number of adverse device effects (ADE) during the clinical trial |
| Unanticipated Adverse Device Effects (UADE) | 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 |
| Mean CGM Glucose Level | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Mean CGM glucose level during AID use |
| Overnight Time in Target Glucose Range | 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 |
| Postprandial Time in Target Glucose Range | 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 meals and 2 hours following meals |
| Glucose < 54 mg/dL | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Percent time CGM glucose \< 54 mg/dL |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maternal Outcomes: Gestational Hypertension | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Number of subjects who develop gestational hypertension during pregnancy |
| Maternal Outcomes: Pre-eclampsia | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Number of subjects who develop pre-eclampsia during pregnancy |
| Maternal Outcomes: Eclampsia | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Number of subjects who develop eclampsia during pregnancy |
| Maternal Outcomes: Oligo/Polyhydramnios | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Number of subjects who develop oligo/polyhydramnios during pregnancy |
| Maternal Outcomes: Pre Term Labor | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Number of subjects who develop pre term labor during pregnancy |
| Maternal Outcomes: Primary Caesarian Section | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Number of subjects who underwent primary caesarian section |
| Fetal Outcomes: Large for Gestational Age | At Delivery | Number of infants born large for gestational age |
| Fetal Outcomes: Neonatal Hypoglycemia | At delivery and up to 48 hours afterwards | 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. |
| Fetal Outcomes: Neonatal Intensive Care Unit Admission | At delivery and up to 7 days afterwards | Number of infants who are admitted to the neonatal intensive care unit |
| Closed-Loop Active Time | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Percent time (hours/day) of closed-loop use during the clinical trial |
| Sensor Use Time | Duration of iAPS Use During Pregnancy up to 40 weeks of Use | Percent Time CGM during the clinical trial |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | AID Evaluation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 32.6 years STANDARD_DEVIATION 4.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Glycated Hemoglobin | 5.8 percentage of glycated hemoglobin STANDARD_DEVIATION 0.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 6 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
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
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AID Evaluation | Time in Target Glucose Range | 78.6 percent time | Standard Deviation 9.2 |
Secondary
Adverse Device Effects (ADE)
The total number of adverse device effects (ADE) during the clinical trial
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
Population: Infusion Set Failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AID Evaluation | Adverse Device Effects (ADE) | 2 Events |
Secondary
Glucose > 140 mg/dL
Percent time GGM glucose \> 140 mg/dL
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AID Evaluation | Glucose > 140 mg/dL | 19.7 percent time | Standard Deviation 9.5 |
Secondary
Glucose > 180 mg/dL
Percent time GGM glucose \> 180 mg/dL
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AID Evaluation | Glucose > 180 mg/dL | 3.4 percent time |
Secondary
Glucose > 250 mg/dL
Percent time GGM glucose \> 250 mg/dL
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AID Evaluation | Glucose > 250 mg/dL | 0.2 percent time |
Secondary
Glucose < 54 mg/dL
Percent time CGM glucose \< 54 mg/dL
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AID Evaluation | Glucose < 54 mg/dL | 0.4 percent time |
Secondary
Glucose < 63 mg/dL
Percent time CGM glucose \< 63 mg/dL
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AID Evaluation | Glucose < 63 mg/dL | 1.6 percent time |
Secondary
Hyperglycemic Events
Number of episodes with ketones \>1 mmol/L
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AID Evaluation | Hyperglycemic Events | 0.2 Number of Events | Standard Deviation 0.42 |
Secondary
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.
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AID Evaluation | Hypoglycemic Events Per Week | 0.7 events per week | Standard Deviation 0.6 |
Secondary
Mean CGM Glucose Level
Mean CGM glucose level during AID use
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AID Evaluation | Mean CGM Glucose Level | 115.1 mg/dL | Standard Deviation 10.6 |
Secondary
Overnight Time in Target Glucose Range
Sensor glucose time within the target range of 63-140 mg/dl overnight
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AID Evaluation | Overnight Time in Target Glucose Range | 84.8 percent time | Standard Deviation 7.7 |
Secondary
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
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AID Evaluation | Postprandial Time in Target Glucose Range | 73.4 percent time | Standard Deviation 11 |
Secondary
Serious Adverse Device Events (SADE)
The total number of serious adverse events related to the study device use during the clinical trial
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AID Evaluation | Serious Adverse Device Events (SADE) | 0 Events |
Secondary
Serious Adverse Events (SAE)
The total number of serious adverse events during the clinical trial
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AID Evaluation | Serious Adverse Events (SAE) | 0 Events |
Secondary
Severe Hypoglycemic Events
Number of hypoglycemic events that events that require active assistance of another individual
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AID Evaluation | Severe Hypoglycemic Events | 0 Number of Events | Standard Deviation 0 |
Secondary
Unanticipated Adverse Device Effects (UADE)
The total number of unanticipated adverse device effects (UADE) during the clinical trial
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AID Evaluation | Unanticipated Adverse Device Effects (UADE) | 0 Events |
Other Pre-specified
Closed-Loop Active Time
Percent time (hours/day) of closed-loop use during the clinical trial
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AID Evaluation | Closed-Loop Active Time | 94.1 percent time | Standard Deviation 4.2 |
Other Pre-specified
Fetal Outcomes: Large for Gestational Age
Number of infants born large for gestational age
Time frame: At Delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AID Evaluation | Fetal Outcomes: Large for Gestational Age | 3 Participants |
Other Pre-specified
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.
Time frame: At delivery and up to 48 hours afterwards
Population: No IV glucose was given, all treated with glucose gel.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AID Evaluation | Fetal Outcomes: Neonatal Hypoglycemia | 3 Participants |
Other Pre-specified
Fetal Outcomes: Neonatal Intensive Care Unit Admission
Number of infants who are admitted to the neonatal intensive care unit
Time frame: At delivery and up to 7 days afterwards
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AID Evaluation | Fetal Outcomes: Neonatal Intensive Care Unit Admission | 1 Participants |
Other Pre-specified
Maternal Outcomes: Eclampsia
Number of subjects who develop eclampsia during pregnancy
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AID Evaluation | Maternal Outcomes: Eclampsia | 0 Participants |
Other Pre-specified
Maternal Outcomes: Gestational Hypertension
Number of subjects who develop gestational hypertension during pregnancy
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AID Evaluation | Maternal Outcomes: Gestational Hypertension | 1 Participants |
Other Pre-specified
Maternal Outcomes: Oligo/Polyhydramnios
Number of subjects who develop oligo/polyhydramnios during pregnancy
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AID Evaluation | Maternal Outcomes: Oligo/Polyhydramnios | 0 Participants |
Other Pre-specified
Maternal Outcomes: Pre-eclampsia
Number of subjects who develop pre-eclampsia during pregnancy
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AID Evaluation | Maternal Outcomes: Pre-eclampsia | 0 Participants |
Other Pre-specified
Maternal Outcomes: Pre Term Labor
Number of subjects who develop pre term labor during pregnancy
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AID Evaluation | Maternal Outcomes: Pre Term Labor | 0 Participants |
Other Pre-specified
Maternal Outcomes: Primary Caesarian Section
Number of subjects who underwent primary caesarian section
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AID Evaluation | Maternal Outcomes: Primary Caesarian Section | 3 Participants |
Other Pre-specified
Sensor Use Time
Percent Time CGM during the clinical trial
Time frame: Duration of iAPS Use During Pregnancy up to 40 weeks of Use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AID Evaluation | Sensor Use Time | 98.5 percent time | Standard Deviation 0.6 |