Real-time Continuous Glucose Monitoring

Real-time Continuous Glucose Monitoring for the Treatment of Gestational Diabetes: a Randomized Trial

Gestational diabetes (GDM) is a condition of carbohydrate intolerance with onset or first recognition in pregnancy. The prevalence of GDM is as high as 25% in some populations and continues to rise with the increase in obesity and type-2 diabetes. GDM places the pregnancy at great risk to both the mother and the neonate. Recent studies have proven that interventions including dietary and medications lower the risk to the pregnancy. Both the American College of Obstetrics and Gynecology (ACOG) and the American Diabetes Association (ADA) recommend dietary interventions with daily glucose monitoring as the initial treatment of choice. Meanwhile, outside of pregnancy, promising new technologies such as continuous glucose monitors (CGM) are revolutionizing diabetic care. The investigators seek to determine if the constant feedback of a real-time CGM system would improve glycemic control compared to traditional management in GDM

Study Overview

• Status: Unknown
• Conditions: Gestational Diabetes
• Intervention / Treatment: Device: Continuous glucose monitoring

Detailed Description

The investigators' proposed study will add new information to the emerging use of CGM in pregnant women with GDM. First, most studies only use CGM for 48 - 72hours at a time, while the investigators will be using CGM for 7 day intervals. Both groups will use the same Enlite sensor (Medtronic). The blinded CGM group will be using the Medtronic iPro2 system (Enlite sensor + transmitter). The real-time CGM group will be using the 530g system (iPro2 (Enlite sensor + transmitter) + inactivated 530g pump set only to display glucose values, no insulin will be administered). This CGM system has been FDA approved to for up to 7 days between sensor changes.26,27 Second, no previous study has used real time CGM in pregnant patients with GDM in the US. The investigators will be the first to describe the use of this technology in this patient population. Third, most of these trials have been performed on populations that are not representative of the investigators' patient population at EVMS. This will be the largest US study of CGM in GDM. Fourth wearable medical and fitness technology is already popular, but as both the technology and the demand continues to grow, it will become the future of diabetes management. Studies have already shown that real time CGM is an effective educational and motivational tool in type-1 and type-2 DM.28,29

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joanne Audouin, MS; Phone Number: 757-446-5121; Email: audouij@evms.edu
• Study Contact Backup: Name: Andrew Lane, MD; Phone Number: 864-608-4134; Email: laneas@evms.edu

Study Locations

• United States
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Eastern Virginia Medical School
      • Sub-Investigator: Alfred Abuhamad, MD
      • Contact: Joanne Audouin, MS; Phone Number: 757-446-5121; Email: audouij@evms.edu
      • Contact: Andrew Lane, MD; Phone Number: 864-608-4134; Email: laneas@evms.edu
      • Principal Investigator: Malgorzata Mlynarczyk, MD, PhD
      • Sub-Investigator: Andrew Lane, MD
      • Sub-Investigator: Margarita de Veciana, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• maternal age 18 to 45
• singleton gestation
• gestational age less than 32 weeks gestation at study inclusion
• BMI less than 45
• 50g glucose challenge greater than 135 mg/dL
• 100 g 3 hr oral glucose tolerance test greater than 2 abnormal values using the Carpenter Coustan cut offs (fasting greater than 95 mg/dL, 1 hr greater than 180 mg/dL, 2 hr greater than 155 mg/dL, 3 hr greater than 140 mg/dL)
• attended the maternal-fetal medicine diabetes education class

Exclusion Criteria:

• maternal age less than18 or greater than 45
• multifetal gestation
• gestational age greater than 32 weeks study inclusion
• BMI greater than 45
• pregestational diabetes
• gestational diabetes diagnosed before 24 weeks
• did not attend the diabetes education class
• known fetal anomaly
• known fetal aneuploidy
• required ongoing treatment with medications that can exacerbate hyperglycemia (steroids, hydroxyprogesterone caproate injections (Makena), highly active antiretroviral therapy HIV medications)
• learning disability
• concern for non compliance with medical care
• imminent preterm delivery due to maternal disease or fetal conditions
• is not willing to wear CGM

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blinded continuous glucose monitoring; The blinded CGM group will be using the Medtronic iPro2 system (Enlite sensor + iPro2 transmitter).	Device: Continuous glucose monitoring; The blinded CGM group will be using the Medtronic iPro2 system (Enlite sensor + iPro2 transmitter). The real-time CGM group will be using the 530g system (inactivated 530g insulin pump (no insulin used, only used as display for CGM), Enlite sensor, MiniLink transmitter)
Experimental: Real time continuous glucose monitoring; The real-time CGM group will be using the 530g system (inactivated 530g insulin pump (no insulin used, only used as display for CGM), Enlite sensor, MiniLink transmitter)	Device: Continuous glucose monitoring; The blinded CGM group will be using the Medtronic iPro2 system (Enlite sensor + iPro2 transmitter). The real-time CGM group will be using the 530g system (inactivated 530g insulin pump (no insulin used, only used as display for CGM), Enlite sensor, MiniLink transmitter)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean blood glucose (mg/dL)	Mean blood glucose (mg/dL) in the real-time CGM group compared to self-monitoring of blood glucose (SMBG) group during the 4th week of study from data collected on the 6 day of CGM use during that week.	week 1 vs. week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failed dietary therapy	Failed dietary therapy (started on medication),	week 1 vs. week 4
Time spent in normoglycemia	Time spent in normoglycemia (min/day)	week 1 vs. week 4
Time spent in hypoglycemia	Time spent in hypoglycemia (min/day)	week 1 vs. week 4
BMI at time of delivery	BMI at time of delivery (kg/m2)	BMI at time of delivery
Gestational hypertension	Gestational hypertension (defined as systolic blood pressure > 140 mm Hg or diastolic blood pressure > 90 mmg Hg, on 2 occasions at least 4 hrs apart	enrollement vs delivery.
Preeclampsia	Preeclampsia (defined as gestational hypertension plus either new-onset proteinuria (> 300 mg/24 2hrs, protein:creatinine > 0.3 mg/dL), thrombocytopenia (platelet count < 100,000/uL), elevated Aspartate aminotransferase or alanine aminotransferase (> 2x upper limit of normal), renal insufficiency (serum creatinine > 1.1 mg/dL or an unexplained doubling of creatinine), pulmonary edema, or cerebral or visual symptoms	enrollement vs delivery.
HbA1C values	HbA1C values (%)	HbA1C values week 1 compared to week 4 (%)
Polyhydramnios	Polyhydramnios (MVP > 8 cm at any point in the pregnancy)	Through study completion, an average of 9 months
Cesarean delivery	Cesarean delivery (w/ indication: macrosomia, malpresentation, failed induction, fetal distress, failed trial of labor after cesarean, scheduled repeat, other)	Delivery
Induction of labor	Induction of labor (w/ indication)	Delivery
Operative vaginal delivery	Operative vaginal delivery (yes/no) and type (forceps/vacuum)	Delivery
Shoulder dystocia	Shoulder dystocia (diagnosed clinically)	Delivery
Fetal macrosomia	Fetal macrosomia (> 4,000g at 38 wk u/s)	Most recent ultrasound before delivery
3rd or 4th degree perineal laceration	3rd or 4th degree perineal laceration at time of delivery	Delivery
Gestational age at delivery	Gestational age at delivery (weeks, days)	Delivery
Preterm delivery	Preterm delivery (< 37 weeks gestational age at birth)	Delivery
Birth weight	Birth weight (grams)	Delivery
Perinatal morbidity composite outcome	Hypoglycemia (yes/no): < 2 hrs after birth and before feeding, defined as < 35mg/dL; Hyperbilirubinemia (yes/no): collected 16-36 hrs after birth, defined as > 95% for any given point after birth requiring phototherapy according to American Academy of Pediatrics guidelines; Birth trauma (yes/no): brachial plexus injury or clavicular, humeral, or skull fracture; Intrauterine fetal demise or neonatal death (yes/no): prior to hospital discharge	Delivery
Large for gestational age	Large for gestational age (yes/no): defined as birth weight > 90%	Delivery
Small for gestational age	Small for gestational age (yes/no): defined as birth weight < 10%	Delivery
Admission to neonatal intensive care unit	Admission to neonatal intensive care unit (yes/no) and length of neonatal intensive care unit stay (days)	Delivery
Respiratory distress syndrome	Respiratory distress syndrome (defined as need to supplemental oxygen > 4 hrs after birth)	Delivery

Collaborators and Investigators

• Sponsor: Eastern Virginia Medical School
• Collaborators: Medtronic
• Investigators: Principal Investigator: Malgorzata Mlynarczyk, MD, PhD, Eastern Virginia Medical School

Publications and helpful links

General Publications

• Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 2003 Mar;111(3):e221-6. doi: 10.1542/peds.111.3.e221.
• Correa A, Bardenheier B, Elixhauser A, Geiss LS, Gregg E. Trends in prevalence of diabetes among delivery hospitalizations, United States, 1993-2009. Matern Child Health J. 2015 Mar;19(3):635-42. doi: 10.1007/s10995-014-1553-5.
• Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005 Mar;115(3):e290-6. doi: 10.1542/peds.2004-1808.
• Murphy HR, Rayman G, Lewis K, Kelly S, Johal B, Duffield K, Fowler D, Campbell PJ, Temple RC. Effectiveness of continuous glucose monitoring in pregnant women with diabetes: randomised clinical trial. BMJ. 2008 Sep 25;337:a1680. doi: 10.1136/bmj.a1680.
• Hartling L, Dryden DM, Guthrie A, Muise M, Vandermeer B, Donovan L. Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research. Ann Intern Med. 2013 Jul 16;159(2):123-9. doi: 10.7326/0003-4819-159-2-201307160-00661.
• Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS; Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005 Jun 16;352(24):2477-86. doi: 10.1056/NEJMoa042973. Epub 2005 Jun 12.
• Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, Wapner RJ, Varner MW, Rouse DJ, Thorp JM Jr, Sciscione A, Catalano P, Harper M, Saade G, Lain KY, Sorokin Y, Peaceman AM, Tolosa JE, Anderson GB; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009 Oct 1;361(14):1339-48. doi: 10.1056/NEJMoa0902430.
• Klonoff DC. Continuous glucose monitoring: roadmap for 21st century diabetes therapy. Diabetes Care. 2005 May;28(5):1231-9. doi: 10.2337/diacare.28.5.1231. No abstract available.
• de Veciana M, Major CA, Morgan MA, Asrat T, Toohey JS, Lien JM, Evans AT. Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. N Engl J Med. 1995 Nov 9;333(19):1237-41. doi: 10.1056/NEJM199511093331901.
• HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943.
• Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol. 2013 Aug;122(2 Pt 1):406-416. doi: 10.1097/01.AOG.0000433006.09219.f1.
• Moyer VA; U.S. Preventive Services Task Force. Screening for gestational diabetes mellitus: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014 Mar 18;160(6):414-20. doi: 10.7326/M13-2905.
• England LJ, Dietz PM, Njoroge T, Callaghan WM, Bruce C, Buus RM, Williamson DF. Preventing type 2 diabetes: public health implications for women with a history of gestational diabetes mellitus. Am J Obstet Gynecol. 2009 Apr;200(4):365.e1-8. doi: 10.1016/j.ajog.2008.06.031. Epub 2008 Aug 8.
• Malcolm JC, Lawson ML, Gaboury I, Lough G, Keely E. Glucose tolerance of offspring of mother with gestational diabetes mellitus in a low-risk population. Diabet Med. 2006 May;23(5):565-70. doi: 10.1111/j.1464-5491.2006.01840.x.
• Mastrototaro J, Shin J, Marcus A, Sulur G; STAR 1 Clinical Trial Investigators. The accuracy and efficacy of real-time continuous glucose monitoring sensor in patients with type 1 diabetes. Diabetes Technol Ther. 2008 Oct;10(5):385-90. doi: 10.1089/dia.2007.0291.
• Kestila KK, Ekblad UU, Ronnemaa T. Continuous glucose monitoring versus self-monitoring of blood glucose in the treatment of gestational diabetes mellitus. Diabetes Res Clin Pract. 2007 Aug;77(2):174-9. doi: 10.1016/j.diabres.2006.12.012. Epub 2007 Jan 16.
• Moy FM, Ray A, Buckley BS. Techniques of monitoring blood glucose during pregnancy for women with pre-existing diabetes. Cochrane Database Syst Rev. 2014 Apr 30;(4):CD009613. doi: 10.1002/14651858.CD009613.pub2.
• Porter H, Lookinland S, Belfort MA. Evaluation of a new real-time blood continuous glucose monitoring system in pregnant women without gestational diabetes. A pilot study. J Perinat Neonatal Nurs. 2004 Apr-Jun;18(2):93-102. doi: 10.1097/00005237-200404000-00004.
• McLachlan K, Jenkins A, O'Neal D. The role of continuous glucose monitoring in clinical decision-making in diabetes in pregnancy. Aust N Z J Obstet Gynaecol. 2007 Jun;47(3):186-90. doi: 10.1111/j.1479-828X.2007.00716.x.
• Yu F, Lv L, Liang Z, Wang Y, Wen J, Lin X, Zhou Y, Mai C, Niu J. Continuous glucose monitoring effects on maternal glycemic control and pregnancy outcomes in patients with gestational diabetes mellitus: a prospective cohort study. J Clin Endocrinol Metab. 2014 Dec;99(12):4674-82. doi: 10.1210/jc.2013-4332.
• Alfadhli E, Osman E, Basri T. Use of a real time continuous glucose monitoring system as an educational tool for patients with gestational diabetes. Diabetol Metab Syndr. 2016 Jul 26;8:48. doi: 10.1186/s13098-016-0161-5. eCollection 2016.
• Glowinska-Olszewska B, Tobiaszewska M, Luczynski W, Bossowski A. Monthly use of a real-time continuous glucose monitoring system as an educational and motivational tool for poorly controlled type 1 diabetes adolescents. Adv Med Sci. 2013;58(2):344-52. doi: 10.2478/ams-2013-0024.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2017
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: October 25, 2017
• First Submitted That Met QC Criteria: October 27, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): November 24, 2017
• Last Update Submitted That Met QC Criteria: November 21, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Pregnancy Complications; Diabetes, Gestational
• Other Study ID Numbers: 17-07-FB-0181

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Do not plan to share.

Drug and device information, study documents

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