Clinical trial NCT04902378: Closed-loop Insulin Delivery In Type 1 Diabetes Pregnancies (CIRCUIT)
Official title: Closed-loop Insulin Delivery by Glucose Responsive Computer Algorithms In Type 1 Diabetes Pregnancies (CIRCUIT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Pregnancy Related
Glucose Metabolism Disorders
Metabolic Disease
Endocrine System Diseases
Keywords: Type 1 diabetes, pregnancy, closed-loop, clinical trial
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2021-05-26
Enrollment: 94
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will assess the efficacy of the Tandem t:slim X2 insulin pump with Control IQ technology compared with standard insulin delivery plus CGM in pregnant women with type 1 diabetes.

Detailed description: Pregnant women with type 1 diabetes (T1D) require normal or near normal glucose in order to reduce the risks of birth defects, stillbirth, increased birthweight, neonatal hypoglycemia, neonatal death, preterm delivery and preeclampsia. Reducing maternal glucose is extremely difficult due to an increased risk of maternal hypoglycemia. Only 14% of T1D pregnancies achieve pregnancy guideline recommended glucose control, leading to complications related to high maternal glucose exposure in roughly half of newborns.

Maintaining recommended maternal glucose levels during pregnancy reduces the risk of adverse neonatal outcomes to those similar in pregnancies unaffected by T1D. Most insulin pumps in use today are open-loop systems, which means that the user must program the pump to deliver a pre-set amount of insulin. These insulin delivery methods (MDI and open-loop pumps) are usually inadequate to achieve the optimal glucose control necessary for T1D pregnancies and they impart a large time, effort and emotional burden.

Closed-loop systems have been found to be effective in improving glucose control outside of pregnancy when studied in children and adults. A new hybrid closed-loop system, the Tandem t:slim X2 insulin pump with Control IQ technology, recently became commercially available. Trials have demonstrated the efficacy of the Control IQ algorithm for non-pregnant adults and children. Pregnant women were not included in these trials.

The investigators propose the first randomized controlled trial to evaluate the Tandem t:slim X2 insulin pump with Control IQ technology versus standard insulin delivery (MDI or pump) and CGM in pregnant women with T1D. In this trial, the investigators will assess the efficacy of the Tandem t:slim X2 insulin pump with Control IQ technology compared with standard insulin delivery plus CGM in pregnant women with type 1 diabetes.

We are grateful to Tandem Diabetes Care and Dexcom for in-kind donations to this investigator initiated study.

Eligibility criteria: Inclusion Criteria:

* Between 18 and 45 years of age (inclusive)
* A diagnosis of type 1 diabetes, as defined by Diabetes Canada, for at least 12 months
* A viable singleton pregnancy confirmed by ultrasound, less than 14 weeks gestation
* Currently on intensive insulin therapy (≥ 3 injections, or Continuous subcutaneous insulin infusion (CSII)
* Willingness to use the study devices throughout the trial
* A1c ≥ 6.2% and \<10% measured any time during pregnancy prior to enrollment
* Able to provide informed consent
* Have access to email

Exclusion Criteria:

* Non-type 1 diabetes
* Current treatment with drugs known to interfere with glucose metabolism as judged by the investigator such as high dose systemic corticosteroids
* Known or suspected allergy to insulin
* Women with nephropathy (estimated glomerular filtration rate \[eGFR\] \<45), severe autonomic neuropathy, uncontrolled gastroparesis or severe proliferative retinopathy, as judged by the investigator, that is likely to interfere with the normal conduct of the study and interpretation of study results
* Total daily insulin dose \<8 or \>250 units/day at screening
* Severe visual or hearing impairment, as judged by the investigator to impact treatment compliance
* Unable to communicate effectively in English or French as judged by the investigator
* Current use of Tandem Control IQ, DIY looping system, 670G in Auto Mode, or alternate closed-loop system as judged by the investigator
* Any reason judged by the investigator that would likely interfere with the normal conduct of the study and interpretation of study results

Primary outcomes:
measure: Glycemic control as reflected by percent glucose time-in-range
timeFrame: 16 weeks until 34 weeks gestation
Secondary outcomes:
measure: Percent time spent above target range per day (+/-SD)
timeFrame: 16 weeks gestation until delivery of neonate
measure: Percent time spent below target range per day (+/-SD)
timeFrame: 16 weeks gestation until delivery of neonate
measure: Mean blood glucose measurement at 24 and 34 weeks (+/-SD)
timeFrame: 24 and 34 weeks gestation
measure: Proportion of participants who experience maternal hypoglycemic events
timeFrame: 16 weeks gestation until delivery of neonate
measure: Glycemic variability reflected by the coefficients of variation and standard deviations of CGM data
timeFrame: 16 weeks gestation until delivery of neonate
measure: Diabetes-related distress to the participant
timeFrame: 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
measure: Fear of hypoglycemia
timeFrame: 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
measure: Fear of hyperglycemia
timeFrame: 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
measure: Sleep quality
timeFrame: 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
measure: Health-related quality of life
timeFrame: 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
measure: Work productivity
timeFrame: 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
measure: Diabetes-related distress to the partners
timeFrame: 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
measure: Proportion of participants who experience preeclampsia events
timeFrame: 16 weeks gestation until delivery of neonate
measure: Proportion of participants who experience gestational hypertension events
timeFrame: 16 weeks gestation until delivery of neonate
measure: Proportion of participants who experience worsening chronic hypertension events
timeFrame: 16 weeks gestation until delivery of neonate
measure: Proportion of participants who have caesarean deliveries
timeFrame: 16 weeks gestation until delivery of neonate
measure: Proportion of participants who experience preterm births
timeFrame: Delivery of neonate to 6 weeks postpartum
measure: Proportion of babies born large for gestational age (>90th percentile)
timeFrame: Delivery of neonate
measure: Proportion of babies born small for gestational age (<10th percentile)
timeFrame: Delivery of neonate
measure: Mean neonatal birthweight (+/-SD)
timeFrame: Delivery of neonate
measure: Comparison of birthweight z-score
timeFrame: Delivery of neonate
measure: Proportion of babies born with neonatal hypoglycemia
timeFrame: Delivery of neonate
measure: Proportion of neonates admitted to intensive care unit admission
timeFrame: Delivery of neonate to 6 weeks postpartum
measure: Proportion of participants who experienced pregnancy loss or miscarriage (< 20 weeks, stillbirth ≥20 weeks, neonatal loss up to 28 days)
timeFrame: 7-13 weeks until delivery of neonate + up to 28 days
measure: Proportion of participants who experience episodes of severe hypoglycemia
timeFrame: 7-13 weeks + 6 days gestation until delivery of neonate
measure: Proportion of participants who experience episodes of diabetic ketoacidosis
timeFrame: 7-13 weeks + 6 days gestation until delivery of neonate
measure: Proportion of participants who experience device-related adverse events
timeFrame: 7-13 weeks + 6 days gestation until delivery of neonate
Other outcomes:
Locations:
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Garran
country: Australia
facility: Canberra Hospital
city: Parkville
country: Australia
facility: Royal Women's Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: BC Women's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: London
country: Canada
facility: Lawson Health Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montréal
country: Canada
facility: University of Montreal - CHUM
state: Quebec
city: Quebec City
country: Canada
facility: Université Laval
state: Quebec
Study officials:
affiliation: University of Calgary
name: Lois Donovan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MOUNT SINAI HOSPITAL
name: Denice Feig, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Singh H, Ingersoll K, Gonder-Frederick L, Ritterband L. "Diabetes Just Tends to Take Over Everything": Experiences of Support and Barriers to Diabetes Management for Pregnancy in Women With Type 1 Diabetes. Diabetes Spectr. 2019 May;32(2):118-124. doi: 10.2337/ds18-0035.
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