Early Administration of Long-acting Insulin Treatment of Diabetic Ketoacidosis in Pediatric Type 1 Diabetes

Early Administration of Long-acting Insulin Glargine for the Treatment of Diabetic Ketoacidosis in Pediatric Type 1 Diabetes: A Randomized Double Blind Trial

The management goals of diabetic ketoacidosis (DKA) in the pediatric type 1 diabetes (T1DM) population are fluid and electrolyte repletion, insulin administration, and correction of acidosis in order to stabilize the patient. Traditionally, a rapid-acting insulin IV infusion is begun immediately and continued until the acidosis is corrected and hyperglycemia normalized. Once the acidosis is corrected, patients are able to be transitioned to a subcutaneous insulin regimen.

The role that a subcutaneous long-acting insulin such as glargine has in the acute treatment of DKA has not been extensively studied. While giving glargine during the treatment of DKA is becoming more common place, few studies have examined the potential risks and benefits of its use. This study will investigate the effects of early administration of glargine during DKA in patients with newly diagnosed TIDM.

The design of this study is a prospective, double-blind study of children ages 2-21 who are admitted to the hospital in DKA with a diagnosis of T1DM. The control group will receive all traditional methods of treatment for DKA, including a placebo subcutaneous injection. The study group will receive the same treatment, but will be supplemented with a subcutaneous glargine injection.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 1; Diabetic Ketoacidosis
• Intervention / Treatment: Drug: IV insulin; Other: Electrolyte Correction; Other: Correction of Fluid Loss; Drug: Glargine

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Children's @ Erlanger

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• T1DM
• Hyperglycemia >200 mg/dl
• Bicarbonate ≤ 15 mmol/L
• pH < 7.3
• Ketonemia
• Ketonuria
• Glucosuria
• Admission to PICU (Pediatric Intensive Care Unit)
• Ages 1-21 years

Exclusion Criteria:

• Patients who received glargine within the last 24 hours
• Patients with sepsis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Group; The control group will receive all traditional methods of treatment for DKA including iv insulin, correction of fluid loss, and electrolyte correction, including a placebo subcutaneous injection.	Drug: IV insulin; The intravenous infusion of insulin at a weight-based fixed rate until ketosis has subsided.; Other: Electrolyte Correction; If the potassium level is greater than 6 mEq/L, do not administer potassium supplement. If the potassium level is 4.5-6 mEq/L, administer 10 mEq/h of potassium chloride. If the potassium level is 3-4.5 mEq/L, administer 20 mEq/h of potassium chloride.; Other: Correction of Fluid Loss; Initial correction of fluid loss is either by isotonic sodium chloride solution or by lactated Ringer solution. The recommended schedule for restoring fluids is as follows: Administer 1-3 L during the first hour.; Administer 1 L during the second hour.; Administer 1 L during the following 2 hours; Administer 1 L every 4 hours, depending on the degree of dehydration and central venous pressure readings
Experimental: Treatment Group; The study group will receive the same treatment including iv insulin, correction of fluid loss, and electrolyte correction, but will be supplemented with a subcutaneous glargine injection.	Drug: IV insulin; The intravenous infusion of insulin at a weight-based fixed rate until ketosis has subsided.; Other: Electrolyte Correction; If the potassium level is greater than 6 mEq/L, do not administer potassium supplement. If the potassium level is 4.5-6 mEq/L, administer 10 mEq/h of potassium chloride. If the potassium level is 3-4.5 mEq/L, administer 20 mEq/h of potassium chloride.; Other: Correction of Fluid Loss; Initial correction of fluid loss is either by isotonic sodium chloride solution or by lactated Ringer solution. The recommended schedule for restoring fluids is as follows: Administer 1-3 L during the first hour.; Administer 1 L during the second hour.; Administer 1 L during the following 2 hours; Administer 1 L every 4 hours, depending on the degree of dehydration and central venous pressure readings; Drug: Glargine; The control group will receive all traditional methods of treatment for DKA, including a placebo subcutaneous injection. The study group will receive the same treatment, but will be supplemented with a subcutaneous glargine injection.; Other Names: Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood glucose	Within 3 hrs of arrival

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood glucose	checking for changes in levels after intervention initiation	4 hours after intervention initiation
blood pH		within 3 hours of arrival
blood pH	checking for changes in levels after intervention initiation	4 hours after intervention initiation
blood bicarbonate level		Within 3 hrs of arrival
blood bicarbonate level	checking for changes in levels after intervention initiation	4 hours after intervention initiation
Urinalysis for levels of ketones & glucosuria		Within 3 hrs of arrival
Urinalysis for levels of ketones & glucosuria	checking for changes in levels after intervention initiation	4 hours after intervention initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of PICU Stay		1-2 days
Length of Hospital Stay		1-5 days
Hypoglycemic events	Hypoglycemia is defined as blood glucose less than 70 mg/dL.	length of hospital stay, an expected average of 3 days

Collaborators and Investigators

• Sponsor: Chattanooga-Hamilton County Hospital Authority
• Investigators: Principal Investigator: Rita Shridharani, MD, UTCOMC/ Children's at Erlanger

Publications and helpful links

General Publications

• Shankar V, Haque A, Churchwell KB, Russell W. Insulin glargine supplementation during early management phase of diabetic ketoacidosis in children. Intensive Care Med. 2007 Jul;33(7):1173-1178. doi: 10.1007/s00134-007-0674-3. Epub 2007 May 17.
• Levitsky LL et al. Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents. In: UpToDate, Wolfsdorf J (Ed), UpToDate, Waltham, MA. (Accessed on November 3, 2014.)
• Jeha GS, Haymond Mw. Treatment and complications of diabetic ketoacidosis in children. In: UpToDate, Waltham MA. (Accessed on November 4, 2014.)
• Urakami T, Naito Y, Seino Y. Insulin glargine in pediatric patients with type 1 diabetes in Japan. Pediatr Int. 2014 Dec;56(6):822-828. doi: 10.1111/ped.12379. Epub 2014 Sep 16.
• Hsia E, Seggelke S, Gibbs J, Hawkins RM, Cohlmia E, Rasouli N, Wang C, Kam I, Draznin B. Subcutaneous administration of glargine to diabetic patients receiving insulin infusion prevents rebound hyperglycemia. J Clin Endocrinol Metab. 2012 Sep;97(9):3132-7. doi: 10.1210/jc.2012-1244. Epub 2012 Jun 8.
• 6Lexicomp online

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): February 1, 2019
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: September 9, 2015
• First Submitted That Met QC Criteria: September 11, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Actual): September 23, 2020
• Last Update Submitted That Met QC Criteria: September 21, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Complications; Acid-Base Imbalance; Diabetes Mellitus; Diabetes Mellitus, Type 1; Acidosis; Ketosis; Diabetic Ketoacidosis; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin Glargine
• Other Study ID Numbers: 15-Lantus

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED