Clinical trial NCT03107208: Early Glargine (Lantus) in DKA Management in Children With Type 1 Diabetes
Official title: Management of Diabetic Ketoacidosis in Children: Does Early Glargine Prevent Rebound Hyperglycemia?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Ketoacidosis
Type 1 Diabetes Mellitus
Keywords: DKA
type 1 diabetes
children
continuous glucose monitoring
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2017-04-11
Enrollment: 61
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A frequent complication in the management of diabetic ketoacidosis (DKA) in children with type 1 diabetes is rebound hyperglycemia (blood glucose over 180 mg/dL) which increases the risk of re-developing DKA and can lengthen the hospital stay. The investigators want to study whether giving the long-acting insulin glargine (Lantus®) early in DKA management (versus after complete resolution of the DKA) helps prevent rebound hyperglycemia and makes the transition to insulin injections easier. Participants will also have the option to wear a continuous glucose monitor (CGM) during the study to help us understand blood glucose control during and after DKA.

Detailed description: Diabetic ketoacidosis (DKA) remains the leading cause of morbidity and mortality in children with type 1 diabetes (T1D) and the incidence of T1D is increasing. A frequent complication in DKA management that is associated with in-hospital mortality and longer hospital stay is hyperglycemia; specifically rebound hyperglycemia (defined as a serum glucose greater than 180 mg/dL) within 12-24 hours after correction of the DKA. Rebound hyperglycemia increases the patient's risk of re-developing DKA. Few adult studies suggest that giving the long-acting insulin analog (glargine or Lantus®) early in the management of DKA (i.e. while still receiving intravenous insulin) can reduce rebound hyperglycemia without an increased risk of hypoglycemia and result in a smoother transition from intravenous insulin to subcutaneous insulin. This has not been well-studied in children to date. In this study the investigators want to determine whether giving glargine early in DKA management in children results in reduced rebound hyperglycemia without an increased risk in hypoglycemia. The investigators will do this by randomizing participants in DKA to either receive glargine early in the management of DKA (study group) or after resolution of DKA (control group); the latter is currently standard-of-care. Additionally, continuous glucose monitoring (CGM) systems have not been studied in a pediatric population with DKA. These devices measure blood sugar levels every 5 minutes and provide a great deal of information about blood sugar control patterns over many days. Not only will the use of CGM in this study provide meaningful information regarding blood sugar patterns during DKA treatment, it will also broaden the investigators knowledge of whether CGM is a feasible and accurate tool to use in this setting.

Eligibility criteria: Inclusion Criteria:

1. Age 6-17.9 years at time of enrollment.
2. Known history of type 1 diabetes or presumed new-onset type 1 diabetes.
3. Diagnosis of DKA (serum glucose or fingerstick glucose concentration ≥ 200 mg/dL.
4. Venous pH ≤7.3 and/or serum bicarbonate concentration ≤15 mmol/L.
5. Evidence of ketonemia or ketonuria).

Exclusion Criteria:

1. Participants who present in DKA with conditions that affect neurological function such as:

   1. suspected alcohol or drug use,
   2. severe head trauma,
   3. meningitis, etc., who would not be able to consent/assent for the study.
2. Participants who present in DKA who are showing signs of altered mental status at time of enrollment.
3. Other known complicating illness or poorly-controlled chronic illness that is known to affect blood glucose levels and/or electrolyte balance such as:

   1. chronic renal disease (requiring hemodialysis),
   2. chronic liver disease (with evidence of current hepatic dysfunction,
   3. coagulopathy, and/or chronic hepatitis), or
   4. severe chronic lung disease (requiring the use of oral steroids).
4. Use of medications that are known to affect blood glucose levels such as:

   1. oral glucocorticoids,
   2. Metformin,
   3. SGLT2 inhibitors,
   4. GLP-1 receptor agonists,
   5. DPP-4 inhibitors,
   6. thiazolidinediones
   7. sulfonylureas, and
   8. vasopressors, etc.
5. Participants who have begun DKA treatment prior to being approached for enrollment and have received more than 6 hours of IV insulin therapy.
6. Participants who are known to be pregnant.
7. Participants who have a known diagnosis of type 2 diabetes.
8. Participants for whom the treating physicians feel a specific insulin regimen is necessary such that patient safety or well-being could be compromised by enrollment into the study.

Primary outcomes:
measure: Rate of Rebound Hyperglycemia
timeFrame: Within 12 hours after discontinuation of IV insulin
Secondary outcomes:
measure: Rate of Recurrent Ketogenesis
timeFrame: Within 12 hours after discontinuation of IV insulin
measure: Risk of Hypoglycemia Between Those Given Early Administration of Glargine Versus Those Given Standard-of-care Management.
timeFrame: During treatment and within 12 hours after d/c IV insulin; while receiving IV insulin in children with DKA given early glargine versus standard-of-care management.
measure: Evaluation of CGM and POC Glucose Monitoring During DKA Treatment in Children.
timeFrame: During treatment of DKA and within 12 hours after discontinuation of IV insulin.
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Rebecca Ohman-Hanson
role: PRINCIPAL_INVESTIGATOR
References: