Diazoxide In the Management Of Hypoglycemic Neonates (DIMOHN)

Use for Diazoxide in the Initial Management of Hypoglycemia in Infants of Diabetic Mothers and Infants Large for Gestation

Diazoxide is an oral hyperglycemic medication. Diazoxide has been proven effective for treating hypoglycemia in infants and children with some types of persistent hyperinsulinemic hypoglycemia. The mechanism of action results in decreased insulin secretion. One of the causes of hypoglycemia in infants of diabetic mothers occurs due to a transient hyperinsulinemic state postnatally. The investigators have clinical experience and success using diazoxide in their unit for patients with hypoglycemia not adequately managed with intravenous (iv) dextrose and enteral supplementation. In this randomized controlled study the investigators expect that by using diazoxide as the initial treatment for infants of diabetic mothers with asymptomatic hypoglycemia (blood glucose of 2.5 to 2.0mmol/L), the investigators will be able to decrease the number of infants requiring an intravenous by at least thirty percent.

Study Overview

• Status: Unknown
• Conditions: Hypoglycemia; Infant, Newborn, Diseases; Pregnancy in Diabetics; Infant, Diabetic Mother; Infant, Large for Gestational Age
• Intervention / Treatment: Drug: Diazoxide; Drug: Ora-plus

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Koravangattu Sankaran, MD, BS, FRCPC, F.C.C.M.; Phone Number: 1-306-966-8118; Email: k.sankaran@usask.ca
• Study Contact Backup: Name: Jennifer M Toye, MD, FRCP(C); Phone Number: 1-306-966-8118; Email: jtoye13@gmail.com

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W4
      • Royal University Hospital
      • Contact: Koravangattu Sankaran, MD, FRCPC; Phone Number: 1-306-966-8118; Email: k.sankaran@usask.ca
      • Contact: Carmen Dmytryshyn, RN; Phone Number: 1-306-966-8138
      • Principal Investigator: Koravangattu Sankaran, MD, FRCPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 12 hours (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants of diabetic mothers (IDMs) or infants weighing >90%
• Hypoglycemia: two consecutive blood glucose measurements <2.6mol/L and >1.9mmol/L in the first twelve hours of life
• > 36 weeks gestational age

Exclusion Criteria:

• Infants with symptomatic hypoglycemia (regardless of value
• Infants who meet criteria for intravenous dextrose according to the Canadian Pediatric Society (CPS) position statement
• Infants with contraindications for enteral feeds and/or medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diazoxide; Infants in this are will receive 10mg/kg/d of diazoxide divided and given every eight hours	Drug: Diazoxide; 10mg/kg/d divide every 8 hours; Other Names: Brand Name: Proglycem
Placebo Comparator: Ora-plus; Liquid suspension modified to match intervention. Given every eight hours. Provided in shielded syringes.	Drug: Ora-plus; placebo, give every 8 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood glucose measurement less than 2.0mmol/L	14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of infants with significantly low blood glucose measurements (<1.5mmol/L).	14 days
Length of stay for infants in hospital	14 days
Need for intravenous dextrose infusion to maintain blood glucose above 2.0mmol/L	14 days
Admission to neonatal intensive care unit (NICU)	14 days
Thrombocytopenia and/or Leukopenia	14 days
Electrolyte imbalance requiring clinical intervention (intravenous or oral)	14 days

Collaborators and Investigators

• Sponsor: University of Saskatchewan
• Investigators: Principal Investigator: Koravangattu Sankaran, MD, BS, FRCPC, F.C.C.M., University of Saskatchewan, Department of Pediatrics, Head of Neonatal Research Group

Publications and helpful links

General Publications

• Screening guidelines for newborns at risk for low blood glucose. Paediatr Child Health. 2004 Dec;9(10):723-740. doi: 10.1093/pch/9.10.723. No abstract available.
• Stenninger E, Flink R, Eriksson B, Sahlen C. Long-term neurological dysfunction and neonatal hypoglycaemia after diabetic pregnancy. Arch Dis Child Fetal Neonatal Ed. 1998 Nov;79(3):F174-9. doi: 10.1136/fn.79.3.f174.
• Holtrop PC. The frequency of hypoglycemia in full-term large and small for gestational age newborns. Am J Perinatol. 1993 Mar;10(2):150-4. doi: 10.1055/s-2007-994649.
• Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics. 2000 May;105(5):1141-5. doi: 10.1542/peds.105.5.1141.
• Diwakar KK, Sasidhar MV. Plasma glucose levels in term infants who are appropriate size for gestation and exclusively breast fed. Arch Dis Child Fetal Neonatal Ed. 2002 Jul;87(1):F46-8. doi: 10.1136/fn.87.1.f46.
• Hoseth E, Joergensen A, Ebbesen F, Moeller M. Blood glucose levels in a population of healthy, breast fed, term infants of appropriate size for gestational age. Arch Dis Child Fetal Neonatal Ed. 2000 Sep;83(2):F117-9. doi: 10.1136/fn.83.2.f117.
• Hawdon JM. Hypoglycaemia and the neonatal brain. Eur J Pediatr. 1999 Dec;158 Suppl 1:S9-S12. doi: 10.1007/pl00014319.
• Stenninger E, Schollin J, Aman J. Early postnatal hypoglycaemia in newborn infants of diabetic mothers. Acta Paediatr. 1997 Dec;86(12):1374-6. doi: 10.1111/j.1651-2227.1997.tb14916.x.
• Nold JL, Georgieff MK. Infants of diabetic mothers. Pediatr Clin North Am. 2004 Jun;51(3):619-37, viii. doi: 10.1016/j.pcl.2004.01.003.
• DRASH A, WOLFF F. DRUG THERAPY IN LEUCINE-SENSITIVE HYPOGLYCEMIA. Metabolism. 1964 Jun;13:487-92. doi: 10.1016/0026-0495(64)90133-7. No abstract available.
• Agrawal RK, Lui K, Gupta JM. Neonatal hypoglycaemia in infants of diabetic mothers. J Paediatr Child Health. 2000 Aug;36(4):354-6. doi: 10.1046/j.1440-1754.2000.00512.x.
• Tyrrell VJ, Ambler GR, Yeow WH, Cowell CT, Silink M. Ten years' experience of persistent hyperinsulinaemic hypoglycaemia of infancy. J Paediatr Child Health. 2001 Oct;37(5):483-8. doi: 10.1046/j.1440-1754.2001.00748.x.
• Touati G, Poggi-Travert F, Ogier de Baulny H, Rahier J, Brunelle F, Nihoul-Fekete C, Czernichow P, Saudubray JM. Long-term treatment of persistent hyperinsulinaemic hypoglycaemia of infancy with diazoxide: a retrospective review of 77 cases and analysis of efficacy-predicting criteria. Eur J Pediatr. 1998 Aug;157(8):628-33. doi: 10.1007/s004310050900.
• Dunne MJ, Cosgrove KE, Shepherd RM, Aynsley-Green A, Lindley KJ. Hyperinsulinism in infancy: from basic science to clinical disease. Physiol Rev. 2004 Jan;84(1):239-75. doi: 10.1152/physrev.00022.2003.
• Shirland L. When it is more than transient neonatal hypoglycemia: hyperinsulinemia--a case study challenge. Neonatal Netw. 2001 Jun;20(4):5-11. doi: 10.1891/0730-0832.20.4.5.
• Taketomo CK, Hodding JH, Kraus DM. Pediatric Dosage Handbook 14th edition. Hudson (OH): Lexi-comp, Inc. 2007: 485-6
• McGraw ME, Price DA. Complications of diazoxide in the treatment of nesidioblastosis. Arch Dis Child. 1985 Jan;60(1):62-4. doi: 10.1136/adc.60.1.62.
• Behrman RE, Kliegman R, Jenson HB, StantonBF. Nelson Textbook of Pediatrics 18th Edition. Philadelphia: WB Saunders Company 2007:783-6

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Anticipated): October 1, 2011
• Study Completion (Anticipated): October 1, 2011

Study Registration Dates

• First Submitted: September 30, 2009
• First Submitted That Met QC Criteria: October 10, 2009
• First Posted (Estimate): October 14, 2009

Study Record Updates

• Last Update Posted (Estimate): October 14, 2009
• Last Update Submitted That Met QC Criteria: October 10, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: Hypoglycemia; Infants of Diabetic Mothers; Diazoxide; Large for Gestation Infants
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Pregnancy Complications; Hypoglycemia; Pregnancy in Diabetics; Infant, Newborn, Diseases; Antihypertensive Agents; Vasodilator Agents; Diazoxide
• Other Study ID Numbers: Bio-REB #08-151; HC Control Number: 126963