DETERMINE: Detemir vs NPH (DETERMINE)

A Phase 2 Open Label Randomized Controlled Trial Determir Vs Neutral Protamine Hagedorn (NPH) In Pregnant Women: DETERMINE Study

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

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Gestational Diabetes
• Intervention / Treatment: Drug: Insulin Detemir; Drug: Insulin NPH

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.

• Study Type: Interventional
• Enrollment (Estimated): 336
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Richley, MD; Phone Number: 310-794-7274; Email: mrichley@mednet.ucla.edu
• Study Contact Backup: Name: Christina Han, MD; Phone Number: 310-794-7274; Email: cshan@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90069
      • Recruiting
      • University of California, Los Angeles
      • Contact: Christina S Han, MD; Email: cshan@mednet.ucla.edu
      • Contact: Michael A Richley, MD; Email: mrichley@mednet.ucla.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: Insulin Detemir; Patients are to receive insulin detemir as long acting insulin to control blood sugars	Drug: Insulin Detemir; Patients are to receive insulin detemir
Active Comparator: Insulin NPH; Patients are to receive insulin NPH as long acting insulin to control blood sugars	Drug: Insulin NPH; Patients are to receive insulin NPH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal Hypoglycemia	Rate (%) of neonatal hypoglycemia	Within the first 24 hours of life
Prolonged neonatal hypoglycemia	Rate (%) of prolonged neonatal hypoglycemia	Neonatal hypoglycemia after the 1st 24 hours of life but before discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal Gastrin Level	Sample form cord blood	At birth
Neonatal C-Peptide Level	Sample from cord blood	At birth
Neonatal insulin level	Sample from cord blood	At birth
Neonatal leptin level	Sample from cord blood	At birth
Rates of pregnancy induced hypertension	Maternal rates of preeclampsia, eclampsia, or gestational hypertension	1 year
Mode of delivery	Spontaneous vaginal, operative vaginal, cesarean	At delivery
Gestational Age at delivery	Gestational Age at delivery	At delivery
Maternal glycemic control	Rate (%) of in range maternal blood glucose control in antepartum period	1 year
Total daily insulin	Total daily insulin dose in patient	1 year
Fetal anomolies	Rate (%) of fetal anomolies	At birth
Macrosomia	Rate (%) of macrosomia	At birth
Polyhydramnios	Rate (%) of polyhydramnios	At birth
Neonatal weight	Neonatal weight	At birth
Need for supplemental oxygen	Rate of supplemental oxygen use (%) in neonate	1 year
Need for dextrose infusion in neonate	Rate of dextrose infusion use (%) in neonate	1 year
Rates of respiratory distress syndrome	Rate of RDS (%) in neonate	1 year
5 Minute APGAR	5 Minute APGAR	At birth

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Christina Han, MD, University of California, Los Angeles; Study Director: Michael Richley, MD, University of California, Los Angeles

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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. Erratum In: Diabetes Care. 2018 Jan 8;:
• 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.
• 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.

Helpful Links

• Abstract
• Abstract

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 18, 2021

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes, Gestational; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Detemir; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: DETERMINE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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