Use of NPH Versus Basal Bolus Insulin for Steroid Induced Hyperglycemia

NCT03511521 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: STU00207079
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Glucocorticoids are known to cause an increase in insulin resistance, leading to hyperglycemia, in both diabetic and non-diabetic patients. In both the inpatient and outpatient setting, steroids are used for their anti-inflammatory property to treat a variety of conditions. There is a paucity of information regarding the best way to treat steroid-induced hyperglycemia. In this study we will compare (1) the addition of NPH insulin, an intermediate-acting insulin, given at the time of steroid administration to the patient's standard basal/bolus insulin to (2) modification of the standard basal-bolus insulin regimen which will consist primarily increasing the prandial doses at lunch and supper in order to determine which regimen is superior for glycemic control.

Conditions

Hyperglycemia Steroid-induced; Insulin Resistance, Diabetes

Keywords

steroid; prednisone; methylprednisolone; hyperglycemia; insulin; hypoglycemia

Outcome Measures

Primary Outcomes (1)

• Glycemic Control

  mean of 4 glucose levels per day (premeal and bedtime) for each group for first 3 days after intervention

  3 days

Secondary Outcomes (2)

• Percentage of Glucose Values Within Therapeutic Range

  3 days

• Percentage of Glucose Values Within the Hypoglycemic Range

  3 days

Study Arms (2)

NPH Insulin

EXPERIMENTAL

NPH will be given at the time of steroid administration to the patient in addition to standard basal/bolus insulin the patient may be receiving in the following doses: Prednisone Dose (mg/day) - NPH dose (U=Units): 10-20 mg/day - 1.2U (units)/mg; 21-40 mg/day - 0.6U/mg; 41-60 mg/day - 0.45U/mg; 61-80 mg/day - 0.3U/mg; \>80 mg/day - no additional NPH. Note that the amounts of NPH are added to each other for the various prednisone doses. For example, a dose of 75 mg/day of prednisone would come out to be (1.2U x 20mg = 24U) + (0.6U x 20mg = 12U) + (0.45U x 20mg = 9U) + 0.3U x 15 mg = 4.5U) for a total of 24 + 12 + 9 + 4.5 = 49.5U of NPH for 75 mg of prednisone.

Drug: NPH Insulin; Drug: glargine; Drug: Insulin Aspart

Basal/Bolus Insulin

ACTIVE COMPARATOR

Basal insulin (glargine) and Bolus insulin (insulin aspart) will be increased (doses given in U \[units\]/kg) according to the Prednisone dose (mg/day) as follows: Prednisone Dose (mg/day) - doses of insulin (U/kg): Prednisone 0 mg - Glargine 0.25U/kg, Bkfst Aspart 0.08U/kg, Lunch Aspart 0.08U/kg, Dinner Aspart - 0.08U/kg; Prednisone 10-20 mg - Glargine 0.25U/kg, Bkfst Aspart 0.1U/kg, Lunch Aspart 0.15U/kg, Dinner Aspart - 0.2U/kg; Prednisone 21-40 mg - Glargine 0.25U/kg, Bkfst Aspart 0.1U/kg, Lunch Aspart 0.2U/kg, Dinner Aspart - 0.25U/kg; Prednisone 41-60 mg - Glargine 0.30U/kg, Bkfst Aspart 0.15U/kg, Lunch Aspart 0.25U/kg, Dinner Aspart - 0.30U/kg; Prednisone 61-80 mg - Glargine 0.30U/kg, Bkfst Aspart 0.15U/kg, Lunch Aspart 0.30U/kg, Dinner Aspart - 0.35U/kg; Prednisone \>80 mg - Glargine 0.30U/kg, Bkfst Aspart 0.15U/kg, Lunch Aspart 0.35U/kg, Dinner Aspart - 0.40U/kg.

Drug: glargine; Drug: Insulin Aspart

Interventions

NPH Insulin DRUG

Intermediate acting insulin

Also known as: Humulin N, Novolin N

NPH Insulin

glargine DRUG

basal insulin

Also known as: Lantus, Basaglar

Basal/Bolus Insulin; NPH Insulin

Insulin Aspart DRUG

prandial insulin

Also known as: Novolog

Basal/Bolus Insulin; NPH Insulin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients receiving once daily dosing of methylprednisolone or prednisone in a dose of 10 mg/day or greater
• Hyperglycemic (Glucose level \> 126 mg/dL)
• Diabetic and nondiabetic patients
• Expected duration of hospital stay and time on steroids \>= 3 days
• Patient of appropriate caregiver able to give Informed Consent

You may not qualify if:

• Patients with 2 or more doses of methylprednisolone/prednisone per day
• Steroids other than methylprednisolone or prednisone
• Pregnancy
• estimated glomerular filtration rate (eGFR) \< 45 ml/min/1.73m2

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Related Publications (5)

• Dhital SM, Shenker Y, Meredith M, Davis DB. A retrospective study comparing neutral protamine hagedorn insulin with glargine as basal therapy in prednisone-associated diabetes mellitus in hospitalized patients. Endocr Pract. 2012 Sep-Oct;18(5):712-9. doi: 10.4158/EP11371.OR.

  PMID: 22784834 RESULT

• Ruiz de Adana MS, Colomo N, Maldonado-Araque C, Fontalba MI, Linares F, Garcia-Torres F, Fernandez R, Bautista C, Olveira G, de la Cruz JL, Rojo-Martinez G, Valdes S. Randomized clinical trial of the efficacy and safety of insulin glargine vs. NPH insulin as basal insulin for the treatment of glucocorticoid induced hyperglycemia using continuous glucose monitoring in hospitalized patients with type 2 diabetes and respiratory disease. Diabetes Res Clin Pract. 2015 Nov;110(2):158-65. doi: 10.1016/j.diabres.2015.09.015. Epub 2015 Sep 30.

  PMID: 26474657 RESULT

• Radhakutty A, Stranks JL, Mangelsdorf BL, Drake SM, Roberts GW, Zimmermann AT, Stranks SN, Thompson CH, Burt MG. Treatment of prednisolone-induced hyperglycaemia in hospitalized patients: Insights from a randomized, controlled study. Diabetes Obes Metab. 2017 Apr;19(4):571-578. doi: 10.1111/dom.12859. Epub 2017 Feb 17.

  PMID: 27995731 RESULT

• Bevier WC, Zisser HC, Jovanovic L, Finan DA, Palerm CC, Seborg DE, Doyle FJ 3rd. Use of continuous glucose monitoring to estimate insulin requirements in patients with type 1 diabetes mellitus during a short course of prednisone. J Diabetes Sci Technol. 2008 Jul;2(4):578-83. doi: 10.1177/193229680800200408.

  PMID: 19885233 RESULT

• Seggelke SA, Gibbs J, Draznin B. Pilot study of using neutral protamine Hagedorn insulin to counteract the effect of methylprednisolone in hospitalized patients with diabetes. J Hosp Med. 2011 Mar;6(3):175-6. doi: 10.1002/jhm.874. No abstract available.

  PMID: 21387555 RESULT

MeSH Terms

Conditions

Insulin Resistance; Diabetes Mellitus; Hyperglycemia; Hypoglycemia

Interventions

Insulin, Isophane; Isophane Insulin, Human; Insulin Glargine; Insulin Aspart

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Regular, Human; Insulin; Proinsulin; Insulin, Short-Acting

Results Point of Contact

• Title: Dr. Mark Molitch, Principal Investigator
• Organization: Northwestern University Feinberg School of Medicine

molitch@northwestern.edu

3125034130

Study Officials

• Mark Molitch, MD

  Northwestern University Feinberg School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Patients receiving single dose steroids who become hyperglycemic will be randomized to two treatment arms in a parallel design: (1) NPH added to basal/bolus insulin; (2) increase in doses of basal and bolus insulin

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: April 27, 2018
• Study Start: March 27, 2018
• Primary Completion: August 15, 2019
• Study Completion: August 15, 2019
• Last Updated: September 11, 2020
• Results First Posted: September 11, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)