DETERMINE: Detemir vs NPH

Diabetes Mellitus, Type 2 Clinical Trial

— DETERMINE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05124457
• Other study ID #: DETERMINE
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2022
• Est. completion date: June 2025

Study information

• Verified date: September 2023
• Source: University of California, Los Angeles
• Contact: Michael Richley, MD
• Phone: 310-794-7274
• Email: mrichley[@]mednet.ucla.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 336
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetes, Gestational
• Gestational Diabetes

Intervention

Drug:
• Insulin Detemir
Patients are to receive insulin detemir
• Insulin NPH
Patients are to receive insulin NPH

Locations

Country	Name	City	State
United States	University of California, Los Angeles	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (11)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. Erratum In: Diabetes Care. 2018 Jan 8;: — View 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. — View 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. — View 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neonatal Hypoglycemia	Rate (%) of neonatal hypoglycemia	Within the first 24 hours of life
Primary	Prolonged neonatal hypoglycemia	Rate (%) of prolonged neonatal hypoglycemia	Neonatal hypoglycemia after the 1st 24 hours of life but before discharge
Secondary	Neonatal Gastrin Level	Sample form cord blood	At birth
Secondary	Neonatal C-Peptide Level	Sample from cord blood	At birth
Secondary	Neonatal insulin level	Sample from cord blood	At birth
Secondary	Neonatal leptin level	Sample from cord blood	At birth
Secondary	Rates of pregnancy induced hypertension	Maternal rates of preeclampsia, eclampsia, or gestational hypertension	1 year
Secondary	Mode of delivery	Spontaneous vaginal, operative vaginal, cesarean	At delivery
Secondary	Gestational Age at delivery	Gestational Age at delivery	At delivery
Secondary	Maternal glycemic control	Rate (%) of in range maternal blood glucose control in antepartum period	1 year
Secondary	Total daily insulin	Total daily insulin dose in patient	1 year
Secondary	Fetal anomolies	Rate (%) of fetal anomolies	At birth
Secondary	Macrosomia	Rate (%) of macrosomia	At birth
Secondary	Polyhydramnios	Rate (%) of polyhydramnios	At birth
Secondary	Neonatal weight	Neonatal weight	At birth
Secondary	Need for supplemental oxygen	Rate of supplemental oxygen use (%) in neonate	1 year
Secondary	Need for dextrose infusion in neonate	Rate of dextrose infusion use (%) in neonate	1 year
Secondary	Rates of respiratory distress syndrome	Rate of RDS (%) in neonate	1 year
Secondary	5 Minute APGAR	5 Minute APGAR	At birth

External Links

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