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

Tracking Information

• First Submitted Date: October 25, 2021
• First Posted Date: November 18, 2021
• Last Update Posted Date: September 26, 2023
• Actual Study Start Date: February 1, 2022
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 5, 2021)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 5, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

Condition

• Gestational Diabetes
• Diabetes Mellitus, Type 2

Intervention

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

Study Arms

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

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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 5, 2021): 336
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2025
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05124457
• Other Study ID Numbers: DETERMINE
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Christina S. Han, University of California, Los Angeles
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, Los Angeles
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of California, Los Angeles
• Verification Date: September 2023