Closed-loop Insulin Delivery In Type 1 Diabetes Pregnancies (CIRCUIT)

Pregnancy Related Clinical Trial

— CIRCUIT  

Official title:

Closed-loop Insulin Delivery by Glucose Responsive Computer Algorithms In Type 1 Diabetes Pregnancies (CIRCUIT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04902378
• Other study ID #: REB20-1266
• Status: Recruiting
• Phase: N/A
• Start date: June 15, 2021
• Est. completion date: January 2026

Study information

• Verified date: February 2024
• Source: University of Calgary
• Contact: Lois Donovan, MD
• Phone: 1-403-955-8358
• Email: lois.donovan[@]ahs.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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 = 6.5% 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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes, Gestational
• Endocrine System Diseases
• Glucose Metabolism Disorders
• Metabolic Disease
• Metabolic Diseases
• Pregnancy in Diabetics
• Pregnancy Related
• Type 1 Diabetes Mellitus

Intervention

Device:
• Tandem t:slim X2 insulin pump with Control IQ technology
The intervention group will be fitted with the Tandem t:slim X2 insulin pump with Control IQ technology during pregnancy.

Locations

Country	Name	City	State
Australia	Campbelltown Hospital	Campbelltown
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Canberra Hospital	Garran
Australia	Royal Women's Hospital	Parkville
Australia	Westmead Hospital	Westmead
Canada	University of Calgary	Calgary	Alberta
Canada	Lawson Health Research Institute	London	Ontario
Canada	University of Montreal - CHUM	Montréal	Quebec
Canada	Université Laval	Quebec City	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Sunnybrook	Toronto	Ontario
Canada	BC Women's Hospital	Vancouver	British Columbia
Canada	University of Manitoba	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

Countries where clinical trial is conducted

Australia,  Canada, 

References & Publications (14)

Berg M, Honkasalo ML. Pregnancy and diabetes--a hermeneutic phenomenological study of women's experiences. J Psychosom Obstet Gynaecol. 2000 Mar;21(1):39-48. doi: 10.3109/01674820009075607. — View Citation

Berg M. Pregnancy and diabetes: how women handle the challenges. J Perinat Educ. 2005 Summer;14(3):23-32. doi: 10.1624/105812405X57552. — View Citation

Evers IM, de Valk HW, Visser GH. Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands. BMJ. 2004 Apr 17;328(7445):915. doi: 10.1136/bmj.38043.583160.EE. Epub 2004 Apr 5. — View Citation

Feig DS, Donovan LE, Corcoy R, Murphy KE, Amiel SA, Hunt KF, Asztalos E, Barrett JFR, Sanchez JJ, de Leiva A, Hod M, Jovanovic L, Keely E, McManus R, Hutton EK, Meek CL, Stewart ZA, Wysocki T, O'Brien R, Ruedy K, Kollman C, Tomlinson G, Murphy HR; CONCEPTT Collaborative Group. Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial. Lancet. 2017 Nov 25;390(10110):2347-2359. doi: 10.1016/S0140-6736(17)32400-5. Epub 2017 Sep 15. Erratum In: Lancet. 2017 Nov 25;390(10110):2346. — View Citation

Feig DS, Hwee J, Shah BR, Booth GL, Bierman AS, Lipscombe LL. Trends in incidence of diabetes in pregnancy and serious perinatal outcomes: a large, population-based study in Ontario, Canada, 1996-2010. Diabetes Care. 2014 Jun;37(6):1590-6. doi: 10.2337/dc13-2717. Epub 2014 Apr 4. — View Citation

Gupton A, Heaman M, Cheung LW. Complicated and uncomplicated pregnancies: women's perception of risk. J Obstet Gynecol Neonatal Nurs. 2001 Mar-Apr;30(2):192-201. doi: 10.1111/j.1552-6909.2001.tb01535.x. — View Citation

Langer N, Langer O. Pre-existing diabetics: relationship between glycemic control and emotional status in pregnancy. J Matern Fetal Med. 1998 Nov-Dec;7(6):257-63. doi: 10.1002/(SICI)1520-6661(199811/12)7:63.0.CO;2-H. — View Citation

Maresh MJ, Holmes VA, Patterson CC, Young IS, Pearson DW, Walker JD, McCance DR; Diabetes and Pre-eclampsia Intervention Trial Study Group. Glycemic targets in the second and third trimester of pregnancy for women with type 1 diabetes. Diabetes Care. 2015 Jan;38(1):34-42. doi: 10.2337/dc14-1755. Epub 2014 Nov 3. — View Citation

Murphy HR, Bell R, Cartwright C, Curnow P, Maresh M, Morgan M, Sylvester C, Young B, Lewis-Barned N. Improved pregnancy outcomes in women with type 1 and type 2 diabetes but substantial clinic-to-clinic variations: a prospective nationwide study. Diabetologia. 2017 Sep;60(9):1668-1677. doi: 10.1007/s00125-017-4314-3. Epub 2017 Jun 8. — View Citation

Murphy HR, Roland JM, Skinner TC, Simmons D, Gurnell E, Morrish NJ, Soo SC, Kelly S, Lim B, Randall J, Thompsett S, Temple RC. Effectiveness of a regional prepregnancy care program in women with type 1 and type 2 diabetes: benefits beyond glycemic control. Diabetes Care. 2010 Dec;33(12):2514-20. doi: 10.2337/dc10-1113. — View Citation

Persson M, Norman M, Hanson U. Obstetric and perinatal outcomes in type 1 diabetic pregnancies: A large, population-based study. Diabetes Care. 2009 Nov;32(11):2005-9. doi: 10.2337/dc09-0656. Epub 2009 Aug 12. — View 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. — View Citation

Singh H, Murphy HR, Hendrieckx C, Ritterband L, Speight J. The challenges and future considerations regarding pregnancy-related outcomes in women with pre-existing diabetes. Curr Diab Rep. 2013 Dec;13(6):869-76. doi: 10.1007/s11892-013-0417-5. — View Citation

Tennant PW, Glinianaia SV, Bilous RW, Rankin J, Bell R. Pre-existing diabetes, maternal glycated haemoglobin, and the risks of fetal and infant death: a population-based study. Diabetologia. 2014 Feb;57(2):285-94. doi: 10.1007/s00125-013-3108-5. Epub 2013 Nov 29. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic control as reflected by percent glucose time-in-range	Time in range (3.5 to 7.8 mmol/L) per day assessed by CGM glucose measurement	16 weeks until 34 weeks gestation
Secondary	Percent time spent above target range per day (+/-SD)	Glucose above target range defined as glucose >7.8 mmol/L; Blood glucose will be assessed using CGM data	16 weeks gestation until delivery of neonate
Secondary	Percent time spent below target range per day (+/-SD)	Glucose below target range defined as glucose < 3.5 mmol/L; Blood glucose will be assessed using CGM data	16 weeks gestation until delivery of neonate
Secondary	Mean blood glucose measurement at 24 and 34 weeks (+/-SD)	Blood glucose measured in mmol/L and assessed using CGM data	24 and 34 weeks gestation
Secondary	Proportion of participants who experience maternal hypoglycemic events	Maternal hypoglycemic events defined as =15 minutes with CGM glucose <3.5 mmol/L [level 1] or <2.8 mmol/L [level 2]; Blood glucose will be assessed using CGM data	16 weeks gestation until delivery of neonate
Secondary	Glycemic variability reflected by the coefficients of variation and standard deviations of CGM data	Blood glucose measured in mmol/L and assessed using CGM data	16 weeks gestation until delivery of neonate
Secondary	Diabetes-related distress to the participant	Diabetes-related distress will be assessed four times during the study using the Diabetes Distress Screening Scale (DDSS17)	7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
Secondary	Fear of hypoglycemia	Fear of hypoglycemia will be assessed four times during the study using the Hypoglycemia Fear Survey Questionnaire II (HFSQ II)	7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
Secondary	Fear of hyperglycemia	Fear of hyperglycemia will be assessed four times during the study using the g. Hyperglycemia Fear in Pregnancy Survey	7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
Secondary	Sleep quality	Sleep quality will be assessed at four times during the study using the Modified Pittsburgh Sleep Quality Index (PSQI)	7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
Secondary	Health-related quality of life	Health-related quality of life will be assessed four times during the study using the Euro Quality of life questionnaire (EQ-5D-5L)	7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
Secondary	Work productivity	Work productivity will be assessed four times during the study using the Work Productivity and Activity Impairment survey	7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
Secondary	Diabetes-related distress to the partners	Diabetes-related distress to the partners will be assessed four times during the study using the Partner Diabetes Distress Scale	7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum
Secondary	Proportion of participants who experience preeclampsia events	Preeclampsia is defined as pregnancy =20 wks gestation with SBP =140mmHg and/or DBP =90 mmHg on =2 occasions a minimum of 6 hrs apart and new-onset of proteinuria (defined as urinary excretion =0.3g protein on a 24-hr urine specimen, or = 2+ by urinary dipstick, or =30mg protein/mmol of urinary creatinine by spot testing) OR =1 of the following adverse conditions: Eclampsia (Seizures in pregnancy); Elevated liver function tests (Increased AST and/or ALT >70 IU/L); Decreased platelet count <100 x 109/L; Elevated serum creatinine (>80 µmol/L); Small for gestational age infant (birth weight <10th percentile)	16 weeks gestation until delivery of neonate
Secondary	Proportion of participants who experience gestational hypertension events	Gestational hypertension is defined as a woman =20 weeks gestation with a systolic blood pressure of =140 mm Hg and/or a diastolic blood pressure =90 mm Hg on =2 occasions a minimum of 6 hours apart without proteinuria	16 weeks gestation until delivery of neonate
Secondary	Proportion of participants who experience worsening chronic hypertension events	Chronic hypertension is defined as hypertension that is present at <20 weeks gestation or pre-pregnancy	16 weeks gestation until delivery of neonate
Secondary	Proportion of participants who have caesarean deliveries		16 weeks gestation until delivery of neonate
Secondary	Proportion of participants who experience preterm births	Preterm birth defined as birth occurring <37 weeks gestation	Delivery of neonate to 6 weeks postpartum
Secondary	Proportion of babies born large for gestational age (>90th percentile)		Delivery of neonate
Secondary	Proportion of babies born small for gestational age (<10th percentile)		Delivery of neonate
Secondary	Mean neonatal birthweight (+/-SD)	Birthweight measured in kilograms	Delivery of neonate
Secondary	Comparison of birthweight z-score		Delivery of neonate
Secondary	Proportion of babies born with neonatal hypoglycemia		Delivery of neonate
Secondary	Proportion of neonates admitted to intensive care unit admission	Admission to neonatal intensive care unit admission defined as admission of 24 hours or more	Delivery of neonate to 6 weeks postpartum
Secondary	Proportion of participants who experienced pregnancy loss or miscarriage (< 20 weeks, stillbirth =20 weeks, neonatal loss up to 28 days)		7-13 weeks until delivery of neonate + up to 28 days
Secondary	Proportion of participants who experience episodes of severe hypoglycemia	Severe hypoglycemia defined as a hypoglycemic episode requiring assistance from another person.	7-13 weeks + 6 days gestation until delivery of neonate
Secondary	Proportion of participants who experience episodes of diabetic ketoacidosis	Diabetic ketoacidosis (DKA) is defined as an episode with elevated plasma ketones which can be categorized as possible DKA (mild/ self- treated [plasma ketones 0.6 - 1.5mmol/L], moderate/self-treated (plasma ketones > 1.5mmol/L which resolves without hospital admission), or capillary blood ketones >3.0 mol/L without an anion gap of > 15 with admission to hospital for another reason [i.e. prevention of DKA]) or confirmed DKA (severe, with either plasma ketones > 3.0mmol/L or positive serum ketones with an anion gap (Na -(CI+HC03) > 15 and requiring hospital admission for IV fluids and IV insulin to correct the abnormal metabolic state).	7-13 weeks + 6 days gestation until delivery of neonate
Secondary	Proportion of participants who experience device-related adverse events	Device-related adverse events include skin reactions and insulin delivery failures.	7-13 weeks + 6 days gestation until delivery of neonate