DETERMINE: Detemir vs NPH (DETERMINE)

• ClinicalTrials.gov Identifier: NCT05124457
• Recruitment Status: Recruiting
• First Posted: November 18, 2021
• Last Update Posted: September 26, 2023
• Sponsor: University of California, Los Angeles
• Information provided by (Responsible Party): Christina S. Han, University of California, Los Angeles

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Gestational Diabetes; Diabetes Mellitus, Type 2	Drug: Insulin Detemir; Drug: Insulin NPH	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 336 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomization to receive either insulin NPH or insulin detemir
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Open Label Randomized Controlled Trial Determir Vs Neutral Protamine Hagedorn (NPH) In Pregnant Women: DETERMINE Study
• Actual Study Start Date: February 1, 2022
• Estimated Primary Completion Date: June 2025
• Estimated Study Completion Date: June 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Neonatal Hypoglycemia [ Time Frame: Within the first 24 hours of life ]
   Rate (%) of neonatal hypoglycemia
2. Prolonged neonatal hypoglycemia [ Time Frame: Neonatal hypoglycemia after the 1st 24 hours of life but before discharge ]
   Rate (%) of prolonged neonatal hypoglycemia

Secondary Outcome Measures :

1. Neonatal Gastrin Level [ Time Frame: At birth ]
   Sample form cord blood
2. Neonatal C-Peptide Level [ Time Frame: At birth ]
   Sample from cord blood
3. Neonatal insulin level [ Time Frame: At birth ]
   Sample from cord blood
4. Neonatal leptin level [ Time Frame: At birth ]
   Sample from cord blood
5. Rates of pregnancy induced hypertension [ Time Frame: 1 year ]
   Maternal rates of preeclampsia, eclampsia, or gestational hypertension
6. Mode of delivery [ Time Frame: At delivery ]
   Spontaneous vaginal, operative vaginal, cesarean
7. Gestational Age at delivery [ Time Frame: At delivery ]
   Gestational Age at delivery
8. Maternal glycemic control [ Time Frame: 1 year ]
   Rate (%) of in range maternal blood glucose control in antepartum period
9. Total daily insulin [ Time Frame: 1 year ]
   Total daily insulin dose in patient
10. Fetal anomolies [ Time Frame: At birth ]
    Rate (%) of fetal anomolies
11. Macrosomia [ Time Frame: At birth ]
    Rate (%) of macrosomia
12. Polyhydramnios [ Time Frame: At birth ]
    Rate (%) of polyhydramnios
13. Neonatal weight [ Time Frame: At birth ]
    Neonatal weight
14. Need for supplemental oxygen [ Time Frame: 1 year ]
    Rate of supplemental oxygen use (%) in neonate
15. Need for dextrose infusion in neonate [ Time Frame: 1 year ]
    Rate of dextrose infusion use (%) in neonate
16. Rates of respiratory distress syndrome [ Time Frame: 1 year ]
    Rate of RDS (%) in neonate
17. 5 Minute APGAR [ Time Frame: At birth ]
    5 Minute APGAR

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Michael Richley, MD; 310-794-7274; mrichley@mednet.ucla.edu

Contact: Christina Han, MD; 310-794-7274; cshan@mednet.ucla.edu

Locations

United States, California

University of California, Los Angeles; Recruiting

Los Angeles, California, United States, 90069

Contact: Christina S Han, MD cshan@mednet.ucla.edu

Contact: Michael A Richley, MD mrichley@mednet.ucla.edu

Sponsors and Collaborators

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

More Information

Additional Information:

Abstract 

Abstract 

Publications:

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.

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.

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.

• Responsible Party: Christina S. Han, Maternal-Fetal Medicine Division Director, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT05124457
• Other Study ID Numbers: DETERMINE
• First Posted: November 18, 2021
• Last Update Posted: September 26, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Diabetes, Gestational; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Insulin; Insulin, Globin Zinc; Insulin Detemir; Isophane Insulin, Human; Insulin, Isophane; Isophane insulin, beef; Hypoglycemic Agents; Physiological Effects of Drugs