Clinical trial NCT05124457: DETERMINE: Detemir vs NPH
Official title: A Phase 2 Open Label Randomized Controlled Trial Determir Vs Neutral Protamine Hagedorn (NPH) In Pregnant Women: DETERMINE Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gestational Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2021-11-18
Enrollment: 336
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization to receive either insulin NPH or insulin detemir
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to compare rates of neonatal hypoglycemia with maternal NPH vs determir use.

Detailed description: Insulin detemir has been used and is FDA approved for type 1 diabetes in pregnancy women and its safety has been well established. At this point, the only long or intermediate acting medication that is approved for type 2 diabetes or gestational diabetes is insulin NPH. The most serious side effect of insulin detemir is hypoglycemia but the rates of hypoglycemia are lower when comparted to NPH both during pregnancy and outside of pregnancy. Diabetes mellitus (DM) is the most common diagnosis in pregnancy and its incidence is continuing to increase. Recent epidemiologic reports place the risk of pre-gestational diabetes at 1-2% and gestational diabetes (GDM) at 12.5%. Risk factors for type 2 diabetes (T2DM) and GDM include obesity, hypertension, family history of diabetes, polycystic ovarian syndrome, or excessive weight gain in pregnancy. Suboptimal control of DM in pregnancy confers significant morbidity on both the mother and fetus, including increased risk of preeclampsia, preterm delivery, perineal lacerations, cesarean delivery, neonatal hypoglycemia, and NICU admissions.

Eligibility criteria: Inclusion Criteria:

* Inclusion criteria will include pregnant women with pre-existing T2DM and GDM who requiring insulin to manage their blood sugars in pregnancy.

Exclusion Criteria:

1. Multiple Gestation
2. Type 1 Diabetes mellatus
3. Age \< 18
4. Known or suspected hypersensitivity to NPH or insulin detemir
5. Known fetal major malformations
6. Chronic renal or hepatic insufficiency
7. Known to be HIV, Hepatitis B, or Hepatitis C positive
8. Indication for planned premature delivery (placenta accrete, or prior classical cesarean delivery)
9. Insulin dependent before conception

Primary outcomes:
measure: Neonatal Hypoglycemia
timeFrame: Within the first 24 hours of life
measure: Prolonged neonatal hypoglycemia
timeFrame: Neonatal hypoglycemia after the 1st 24 hours of life but before discharge
Secondary outcomes:
measure: Neonatal Gastrin Level
timeFrame: At birth
measure: Neonatal C-Peptide Level
timeFrame: At birth
measure: Neonatal insulin level
timeFrame: At birth
measure: Neonatal leptin level
timeFrame: At birth
measure: Rates of pregnancy induced hypertension
timeFrame: 1 year
measure: Mode of delivery
timeFrame: At delivery
measure: Gestational Age at delivery
timeFrame: At delivery
measure: Maternal glycemic control
timeFrame: 1 year
measure: Total daily insulin
timeFrame: 1 year
measure: Fetal anomolies
timeFrame: At birth
measure: Macrosomia
timeFrame: At birth
measure: Polyhydramnios
timeFrame: At birth
measure: Neonatal weight
timeFrame: At birth
measure: Need for supplemental oxygen
timeFrame: 1 year
measure: Need for dextrose infusion in neonate
timeFrame: 1 year
measure: Rates of respiratory distress syndrome
timeFrame: 1 year
measure: 5 Minute APGAR
timeFrame: At birth
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Christina Han, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Michael Richley, MD
role: STUDY_DIRECTOR
References:
citation: Coton SJ, Nazareth I, Petersen I. A cohort study of trends in the prevalence of pregestational diabetes in pregnancy recorded in UK general practice between 1995 and 2012. BMJ Open. 2016 Jan 25;6(1):e009494. doi: 10.1136/bmjopen-2015-009494.
citation: Melchior H, Kurch-Bek D, Mund M. The Prevalence of Gestational Diabetes. Dtsch Arztebl Int. 2017 Jul 16;114(24):412-418. doi: 10.3238/arztebl.2017.0412.
citation: Mathiesen ER, Hod M, Ivanisevic M, Duran Garcia S, Brondsted L, Jovanovic L, Damm P, McCance DR; Detemir in Pregnancy Study Group. Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes. Diabetes Care. 2012 Oct;35(10):2012-7. doi: 10.2337/dc11-2264. Epub 2012 Jul 30.
citation: Hirsch IB, Juneja R, Beals JM, Antalis CJ, Wright EE. The Evolution of Insulin and How it Informs Therapy and Treatment Choices. Endocr Rev. 2020 Oct 1;41(5):733-55. doi: 10.1210/endrev/bnaa015.
citation: Herrera KM, Rosenn BM, Foroutan J, Bimson BE, Al Ibraheemi Z, Moshier EL, Brustman LE. Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes. Am J Obstet Gynecol. 2015 Sep;213(3):426.e1-7. doi: 10.1016/j.ajog.2015.06.010. Epub 2015 Jun 9.
citation: Dalgic N, Ergenekon E, Soysal S, Koc E, Atalay Y, Gucuyener K. Transient neonatal hypoglycemia--long-term effects on neurodevelopmental outcome. J Pediatr Endocrinol Metab. 2002 Mar;15(3):319-24. doi: 10.1515/jpem.2002.15.3.319.
citation: O'Neill SM, Kenny LC, Khashan AS, West HM, Smyth RM, Kearney PM. Different insulin types and regimens for pregnant women with pre-existing diabetes. Cochrane Database Syst Rev. 2017 Feb 3;2(2):CD011880. doi: 10.1002/14651858.CD011880.pub2.
citation: Kadakia R, Talbot O, Kuang A, Bain JR, Muehlbauer MJ, Stevens RD, Ilkayeva OR, Lowe LP, Metzger BE, Newgard CB, Scholtens DM, Lowe WL; HAPO Study Cooperative Research Group. Cord Blood Metabolomics: Association With Newborn Anthropometrics and C-Peptide Across Ancestries. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4459-4472. doi: 10.1210/jc.2019-00238.
citation: Lowe WL Jr, Bain JR, Nodzenski M, Reisetter AC, Muehlbauer MJ, Stevens RD, Ilkayeva OR, Lowe LP, Metzger BE, Newgard CB, Scholtens DM; HAPO Study Cooperative Research Group. Maternal BMI and Glycemia Impact the Fetal Metabolome. Diabetes Care. 2017 Jul;40(7):902-910. doi: 10.2337/dc16-2452.
citation: Fishel Bartal M, Ward C, Blackwell SC, Ashby Cornthwaite JA, Zhang C, Refuerzo JS, Pedroza C, Lee KH, Chauhan SP, Sibai BM. Detemir vs neutral protamine Hagedorn insulin for diabetes mellitus in pregnancy: a comparative effectiveness, randomized controlled trial. Am J Obstet Gynecol. 2021 Jul;225(1):87.e1-87.e10. doi: 10.1016/j.ajog.2021.04.223. Epub 2021 Apr 15.
citation: Chun J, Strong J, Urquhart S. Insulin Initiation and Titration in Patients With Type 2 Diabetes. Diabetes Spectr. 2019 May;32(2):104-111. doi: 10.2337/ds18-0005.