Strict Versus Permissive Thresholds for Initiation of Pharmacotherapy in Gestational Diabetes (START 2)

Pregnancy Related Clinical Trial

— START2  

Official title:

Strict Versus Permissive Threshold for Initiation of Pharmacotherapy in Gestational Diabetes Mellitus (GDM) With Continuous Glucose Monitoring Use - A Randomized Control Trial (START 2 Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06419803
• Other study ID #: iRISID-2024-3181
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 27, 2024
• Est. completion date: May 2026

Study information

• Verified date: May 2024
• Source: Thomas Jefferson University
• Contact: Kavisha Khanuja, MD
• Phone: 2159555000
• Email: kxk334[@]jefferson.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of our study is to compare neonatal and maternal outcomes using different thresholds for the initiation and titration of pharmacotherapy for gestational diabetes (GDM). Our goal is to compare a Strict and permissive threshold. The Strict study arm target range will be 65-120 mg/dL, with time in range goal of 70%. The permissive study arm target range will be 65-140 mg/dL, with target time in range goal of 70%.

Description:

Pregnancy is a state of insulin resistance to ensure that the growing fetus has ample nutrition. Gestational Diabetes (GDM) develops in pregnant patients with pancreatic dysfunction that leads to impairment of glucose tolerance.

Various studies have examined the benefit of treatment for GDM, including the 2005 Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) and the 2009 Landon et al randomized controlled trials. These studies found that treatment was associated with a significant reduction in newborn complications of perinatal death, shoulder dystocia, large for gestational age infants, cesarean delivery, and birth trauma. The specific threshold value for initiation and up-titration of medical therapy is unknown. Lack of evidence leads to a wide variation in clinical practice of pharmacological initiation and titration for GDM. A systematic review and meta-analysis by Caissutti in 2019 analyzed criteria for initiating pharmacotherapy for GDM and noted the following: 12 of 15 trials initiated pharmacotherapy after 1-2 abnormal values over 1-2 weeks, 2 studies initiated pharmacotherapy after 50% of overall values were abnormal, and 1 study initiated pharmacotherapy after 30% of overall values were abnormal. However, there have been no randomized controlled trials of head-to-head comparison of different thresholds.

The aim of our study is to compare neonatal and maternal outcomes using different thresholds for the initiation and titration of pharmacotherapy for GDM using continuous glucose monitor. Our goal is to compare a Strict and permissive threshold. The Strict study arm target range will be 65-120 mg/dL, with time in range goal of 70%. The permissive study arm target range will be 65-140 mg/dL, with target time in range goal of 70%.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 430
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Live, non-anomalous fetus

• Literacy in English, Spanish, Mandarin, or Arabic

• Patients are also required to provide consent, demonstrate an understanding of the purpose of the study, and agree to the study protocol.

Exclusion Criteria:

• <18 years at EDD

• pre-existing diabetes or diagnosis of GDM prior to 24 weeks

• multi-fetal gestation

• known major fetal anomaly

• known allergy to insulin

• chronic maternal corticosteroid use

• diagnosis of GDM based on finger sticks alone

• patients who have contraindication to oral glucose tolerance test

• a primary language other than English, Spanish, Mandarin, or Arabic

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes
• Pregnancy Related

Intervention

Drug:
• Insulin
Insulin will be used in gestational diabetics to control blood glucose levels

Locations

Country	Name	City	State
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Rochester Medical Center	Rochester	New York

Sponsors (2)

Lead Sponsor	Collaborator
Thomas Jefferson University	University of Rochester

Country where clinical trial is conducted

United States, 

References & Publications (15)

ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018 Feb;131(2):e49-e64. doi: 10.1097/AOG.0000000000002501. — View Citation

Blum AK. Insulin Use in Pregnancy: An Update. Diabetes Spectr. 2016 May;29(2):92-7. doi: 10.2337/diaspect.29.2.92. Erratum In: Diabetes Spectr. 2016 Aug;29(3):191. — View Citation

Caissutti C, Saccone G, Ciardulli A, Berghella V. Very tight vs. tight control: what should be the criteria for pharmacologic therapy dose adjustment in diabetes in pregnancy? Evidence from randomized controlled trials. Acta Obstet Gynecol Scand. 2018 Mar;97(3):235-247. doi: 10.1111/aogs.13257. Epub 2017 Dec 14. — View Citation

Catalano PM, Hauguel-De Mouzon S. Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic? Am J Obstet Gynecol. 2011 Jun;204(6):479-87. doi: 10.1016/j.ajog.2010.11.039. Epub 2011 Feb 2. — View Citation

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. — View Citation

Davitt C, Flynn KE, Harrison RK, Pan A, Palatnik A. Current practices in gestational diabetes mellitus diagnosis and management in the United States: survey of maternal-fetal medicine specialists. Am J Obstet Gynecol. 2021 Aug;225(2):203-204. doi: 10.1016/j.ajog.2021.04.263. Epub 2021 May 14. No abstract available. — View Citation

Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013 Apr 20;13:59. doi: 10.1186/1471-2431-13-59. — View Citation

Gregory EC, Ely DM. Trends and Characteristics in Gestational Diabetes: United States, 2016-2020. Natl Vital Stat Rep. 2022 Jul;71(3):1-15. — View Citation

Harper LM, Mele L, Landon MB, Carpenter MW, Ramin SM, Reddy UM, Casey B, Wapner RJ, Varner MW, Thorp JM Jr, Sciscione A, Catalano P, Harper M, Saade G, Caritis SN, Sorokin Y, Peaceman AM, Tolosa JE; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Carpenter-Coustan Compared With National Diabetes Data Group Criteria for Diagnosing Gestational Diabetes. Obstet Gynecol. 2016 May;127(5):893-898. doi: 10.1097/AOG.0000000000001383. — View Citation

Harrison RK, Cruz M, Wong A, Davitt C, Palatnik A. The timing of initiation of pharmacotherapy for women with gestational diabetes mellitus. BMC Pregnancy Childbirth. 2020 Dec 11;20(1):773. doi: 10.1186/s12884-020-03449-y. — View Citation

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. — View Citation

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. — View Citation

Landy HJ, Gomez-Marin O, O'Sullivan MJ. Diagnosing gestational diabetes mellitus: use of a glucose screen without administering the glucose tolerance test. Obstet Gynecol. 1996 Mar;87(3):395-400. doi: 10.1016/0029-7844(95)00460-2. — View Citation

Metzger BE, Persson B, Lowe LP, Dyer AR, Cruickshank JK, Deerochanawong C, Halliday HL, Hennis AJ, Liley H, Ng PC, Coustan DR, Hadden DR, Hod M, Oats JJ, Trimble ER; HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcome study: neonatal glycemia. Pediatrics. 2010 Dec;126(6):e1545-52. doi: 10.1542/peds.2009-2257. Epub 2010 Nov 15. — View Citation

Quintanilla Rodriguez BS, Mahdy H. Gestational Diabetes. 2023 Aug 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK545196/ — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neonatal Composite Outcome	Neonatal composite including the following measures: large for gestational age (LGA) of neonate defined as birth weight >90th percentile for gestational age using the Fenton growth chart, hypoglycemia o defined as glucose <40 mg/dL <48 hours after birth or glucose, hyperbilirubinemia, stillbirth or neonatal death, birth trauma	First 28 days of birth
Secondary	Neonatal Outcome: Gestational Age of Birth	Gestational age at delivery in weeks and days	Delivery Time
Secondary	Neonatal Outcome: APGAR Score	Scoring system provided a standardized assessment for infants after delivery from 0-10	At 1 minute of life and at 5 min of life
Secondary	Neonatal Outcome: Birthweight	Birthweight in grams, Macrosomia (birthweight >4000g, Small for gestational age (<10th percentile based on Fenton Growth Charts)	Delivery Time
Secondary	Neonatal Outcome: Respiratory distress	Breathing difficulties after birth requiring supplemental oxygen, mask, intubation, and/or surfactant	Within first 24 hours after delivery
Secondary	Neonatal Outcome: Admission to Neonatal intensive Care Unit	Admission to neonatal intensive care unit (NICU)	From delivery to discharge from NICU
Secondary	Maternal Outcomes: Maternal hypoglycemia	Maternal episode of hypoglycemia < 60 mg/dL throughout the pregnancy	Initiation of insulin to delivery
Secondary	Maternal Outcomes: Shoulder Dystocia	An obstetric emergency where the anterior fetal shoulder becomes stuck on the maternal pubic symphysis, delaying the birth of the baby's body	At Delivery
Secondary	Maternal Outcomes: Obstetric anal sphincter injury (OASIS)	3rd degree and 4th degree perineal injuries	At Delivery
Secondary	Maternal Outcomes: Operative Delivery	Vacuum-assisted and Forcep-assisted vaginal Delivery	At Delivery
Secondary	Maternal Outcomes: Cesarean Delivery	Cesarean birth	At Delivery
Secondary	Maternal Outcomes: Postpartum hemorrhage	Defined as cumulative blood loss =1000 mL, or bleeding associated with signs/symptoms of hypovolemia within 24 hours of the birth process	Within 24 hours of delivery
Secondary	Maternal Outcomes: Hypertensive Disorders of Pregnancy	Hypertensive disorders of pregnancy: gestational hypertension, Preeclampsia without severe features, Pre-eclampsia with severe features, severe range blood pressures defined as (systolic blood pressure =160 mmHg and/or diastolic blood pressure =110 mmHg), symptoms of central nervous dysfunction, thrombocytopenia with Platelet count <100,000 platelets/microL, hepatic abnormalities, kidney impairment, and or pulmonary edema	From gestational age of 20 weeks during pregnancy to 6 weeks postpartum