Longitudinal Observation of Insulin Requirements and Sensor Use in Pregnancy (LOIS-P)

Observational Study of Patient Important Outcomes in Pregnant Patients With Type 1 Diabetes Mellitus on Insulin Pump

The overall goal of this study is to enroll pregnant women with type 1 diabetes and follow their glycemic outcomes prospectively throughout pregnancy and into the post-partum period. The investigators anticipate that when compared to subjects using an Artificial pancreas system (AP) as part of a future protocol, this comparator group of subjects undergoing usual care will exhibit less time in target continuous glucose monitoring (CGM) glucose range defined as 63-140 mg/dL and an increased duration of hypoglycemia with CGM glucose <63 mg/dL.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus; Pregnancy in Diabetics
• Intervention / Treatment: Device: Dexcom G6 CGM

Detailed Description

This is an observational study. Data collected will include records of continuous glucose monitoring (CGM) based glucose, insulin delivery, self-monitoring of blood glucose (SMBG), and maternal and fetal outcomes from pregnant women with type 1 diabetes. These data will be used to: (1) develop and refine algorithms for an AP system tailored to the needs of pregnant women with type 1 diabetes, (2) to serve as a comparator group for concurrent AP protocols, (3) describe Dexcom G6 CGM data throughout the pregnancy, and (4) describe insulin changes which occur in pregnancy.

• Study Type: Observational
• Enrollment (Actual): 25

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 40 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women 18 years of age or older with T1D using an insulin pump

Description

Inclusion Criteria:

• Clinical diagnosis, based on investigator assessment, of T1D for at least one year and using insulin for at least 1 year.

• Criteria for documented hyperglycemia (at least 1 must be met):

  • Fasting glucose ≥126 mg/dL
  • Two-hour OGTT glucose ≥200 mg/dL
  • HbA1c ≥6.5% documented
  • Random glucose ≥200 mg/dL with symptoms
  • No data at diagnosis is available but the participant has a convincing history of hyperglycemia consistent with T1D

• Criteria for requiring insulin at diagnosis (1 must be met):

  • Participant required insulin at diagnosis and continually thereafter.
  • Participant did not start insulin at diagnosis but upon investigator review likely needed insulin (significant hyperglycemia that did not respond to oral agents) and did require insulin eventually and used continually.
  • Participant did not start insulin at diagnosis but continued to be hyperglycemic, had positive islet cell antibodies - consistent with latent autoimmune diabetes in adults (LADA) and did require insulin eventually and used continually.
• Currently using an insulin pump for diabetes management
• Currently using or willing to use an insulin-to-carbohydrate ratio to calculate meal bolus sizes
• Willing to change insulin infusion site at least every 3 days.
• Confirmed pregnancy
• Current gestational age <17 weeks
• Age 18-40 years
• HbA1c <10.0%
• Demonstration of proper mental status and cognition for the study
• Ability to access the internet and upload CGM data remotely if needed
• An understanding of and willingness to follow the protocol and sign the informed consent

Exclusion Criteria:

• 670 G users in Auto mode
• Current gestational age ≥17 weeks
• Cystic fibrosis

• A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:

  • Inpatient psychiatric treatment in the past 6 months
  • Abnormal renal function test results (calculated GFR <60 mL/min/1.73m2); testing required for subjects with diabetes duration of greater than 5 years post onset of puberty
  • Active gastroparesis
  • Abuse of alcohol or recreational drugs
  • Infectious process not anticipated to resolve prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis)
  • Uncontrolled arterial hypertension (Resting diastolic blood pressure >95mmHg and/or systolic blood pressure >160 mmHg) at the time of screening
  • Chronic oral steroid use
• A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the protocol

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
type 1 diabetes and pregnancy; Pregnant women with T1D on insulin pumps (CSII/SAP/PLGS) will be offered enrollment in a prospective study that will capture: 1) Dexcom G6 CGM data, 2) self-monitoring of blood glucose (SMBG), 3) insulin pump settings, 4) insulin delivery records, and 5) maternal and fetal outcomes.	Device: Dexcom G6 CGM; All women in the study will be given Dexcom G6 CGM and a study glucometer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Time in Range Glucose Levels 63-140 mg/dL as Determined by CGM	Time in range defined as 63-140 mg/dL as determined by CGM analysis	Prior to 17 weeks gestation (enrollment) through up to 6 weeks postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Percentage of Time Spent Below Target Glucose (<63 mg/dL) as Determined by CGM	Time spent below target cgm glucose range defined as glucose <63 mg/dL	Prior to 17 weeks gestation (enrollment) through up to 6 weeks postpartum
Percentage of Time Spent Above Target Glucose Range (> 140 mg/dL) as Determined by CGM	Time spent above target cgm glucose range defined as >140 mg/dL	Prior to 17 weeks gestation (enrollment) through up to 6 weeks postpartum
Episodes of Clinically Significant Hyperglycemia	Episodes of clinically significant hyperglycemia with CGM glucose >180 mg/dL	Prior to 17 weeks gestation (enrollment) through up to 6 weeks postpartum
Total Daily Insulin Requirements Over Last 2 Weeks of Third Trimester	Total daily insulin requirements (units/kg/day) over last 2 weeks of third trimester	2 weeks
Basal Insulin Requirements Over Last 2 Weeks of Third Trimester	Basal daily insulin requirements (units/kg/day) over last 2 weeks of third trimester	2 weeks
Carbohydrate Consumption Over Last 2 Weeks of Third Trimester	Carbohydrate consumption (g/(kg*day)) over last 2 weeks of third trimester	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ketoacidosis	Episodes of ketoacidosis requiring emergency room or hospital admission	Prior to 17 weeks gestation (enrollment) through up to 6 weeks postpartum
Maternal Complications	Maternal complications including preeclampsia, pregnancy induced hypertension and polyhydramnios	Prior to 17 weeks gestation (enrollment) through up to 6 weeks postpartum
Gestational Weight Gain	Gestational weight gain each week	Prior to 17 weeks gestation (enrollment) through up to 6 weeks postpartum
Gestational Age at Delivery	Gestational age at delivery (Weeks)	Immediately at birth
Birth Weight of Baby	Birth weight of baby (kg)	Immediately at birth
LGA	Number of Large for Gestational Age based on WHO criteria at time of delivery	Immediately at birth
Preterm Birth	Number of infants born late preterm birth (at 34-37 weeks)	Immediately at birth
Neonatal NICU Stay	Number of infants requiring neonatal NICU stay	Prior to 17 weeks gestation (enrollment) through up to 6 weeks postpartum
Cesarean Delivery	Number of participants that underwent primary cesarean section for delivery	Immediately at birth

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: Yogish C Kudva, MD, Mayo Clinic; Principal Investigator: Barak Rosenn, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Kristin Castorino, DO, Sansum Diabetes Research Institute; Principal Investigator: Grenye O'Malley, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Eyal Dassau, PhD, Harvard University; Principal Investigator: Jordan E Pinsker, MD, Sansum Diabetes Research Institute

Publications and helpful links

General Publications

• O'Malley G, Ozaslan B, Levy CJ, Castorino K, Desjardins D, Levister C, McCrady-Spitzer S, Church MM, Kaur RJ, Reid C, Kremers WK, Doyle FJ, Trinidad MC, Rosenn B, Pinsker JE, Kudva YC, Dassau E. Longitudinal Observation of Insulin Use and Glucose Sensor Metrics in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitors and Insulin Pumps: The LOIS-P Study. Diabetes Technol Ther. 2021 Dec;23(12):807-817. doi: 10.1089/dia.2021.0112. Epub 2021 Aug 17.
• Kaur RJ, Smith BH, Ozaslan B, Pinsker JE, Trinidad MC, O'Malley G, Desjardins D, Castorino KN, Levister C, Reid C, McCrady-Spitzer S, Ogyaadu SJ, Church MM, Piper M, Kremers WK, Rosenn B, Doyle FJ 3rd, Dassau E, Levy CJ, Kudva YC. Hypoglycemia in Prospective Multicenter Study of Pregnancies with Pre-Existing Type 1 Diabetes on Sensor-Augmented Pump Therapy: The LOIS-P Study. Diabetes Technol Ther. 2022 Aug;24(8):544-555. doi: 10.1089/dia.2021.0479.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2018
• Primary Completion (Actual): June 9, 2021
• Study Completion (Actual): June 9, 2021

Study Registration Dates

• First Submitted: November 24, 2018
• First Submitted That Met QC Criteria: November 29, 2018
• First Posted (Actual): December 3, 2018

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: pregnancy; artificial pancreas; type 1 diabetes; continues glucose monitoring
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Pregnancy in Diabetics
• Other Study ID Numbers: 18-007081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Plan to create a public database of study results per NIH open data policy.
• IPD Sharing Time Frame: 1 year after study data analysis is complete and results are published.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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