Use of NPH Versus Basal Bolus Insulin for Steroid Induced Hyperglycemia

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Primary Purpose

Status

Terminated

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

NPH Insulin

glargine

Insulin Aspart

About this trial

This is an interventional treatment trial for Hyperglycemia Steroid-induced focused on measuring steroid, prednisone, methylprednisolone, hyperglycemia, insulin, hypoglycemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Northwestern University Feinberg School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

NPH Insulin

Basal/Bolus Insulin

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Glycemic Control

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

Secondary Outcome Measures

Percentage of Glucose Values Within Therapeutic Range

Percentage of the glucose values (premeal and bedtime for 3 days) within the therapeutic target of 80 - 180 mg/dL

Percentage of Glucose Values Within the Hypoglycemic Range

Percentage of the glucose values (premeal and bedtime for 3 days) less than 70 mg/dL and 54 mg/dL

Full Information

NCT ID

NCT03511521

First Posted

April 18, 2018

Last Updated

August 25, 2020

Sponsor

Northwestern University

1. Study Identification

Unique Protocol Identification Number

NCT03511521

Brief Title

Use of NPH Versus Basal Bolus Insulin for Steroid Induced Hyperglycemia

Official Title

Use of Neutral Protamine Hagedorn (NPH) Versus Basal Bolus Insulin for Steroid Induced Hyperglycemia

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Terminated

Why Stopped

Unable to recruit sufficient number of patients

Study Start Date

March 27, 2018 (Actual)

Primary Completion Date

August 15, 2019 (Actual)

Study Completion Date

August 15, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

4. Oversight

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

Data Monitoring Committee

No

5. Study Description

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.

Detailed Description

Inpatients who will receive single daily doses of prednisone or methylprednisolone for treatment of their underlying condition and who become hyperglycemic will be eligible. Subjects will be randomized in a 1:1 fashion to one of two arms: (1) to their standard basal bolus insulin the addition of NPH insulin given at the time of the steroid adminstration, adjusting the dose based on the dose of steroid; (2) an increase in the basal and prandial bolus insulin doses based on the dose of steroid. Glycemic control and the incidence of hypoglycemia will be assessed over the first 3 days after initiating these insulin regimens.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyperglycemia Steroid-induced, Insulin Resistance, Diabetes

Keywords

steroid, prednisone, methylprednisolone, hyperglycemia, insulin, hypoglycemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

None (Open Label)

Allocation

Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NPH Insulin

Arm Type

Experimental

Arm Description

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.

Arm Title

Basal/Bolus Insulin

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

NPH Insulin

Other Intervention Name(s)

Humulin N, Novolin N

Intervention Description

Intermediate acting insulin

Intervention Type

Drug

Intervention Name(s)

glargine

Other Intervention Name(s)

Lantus, Basaglar

Intervention Description

basal insulin

Intervention Type

Drug

Intervention Name(s)

Insulin Aspart

Other Intervention Name(s)

Novolog

Intervention Description

prandial insulin

Primary Outcome Measure Information:

Title

Glycemic Control

Description

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

Time Frame

3 days

Secondary Outcome Measure Information:

Title

Percentage of Glucose Values Within Therapeutic Range

Description

Percentage of the glucose values (premeal and bedtime for 3 days) within the therapeutic target of 80 - 180 mg/dL

Time Frame

3 days

Title

Percentage of Glucose Values Within the Hypoglycemic Range

Description

Percentage of the glucose values (premeal and bedtime for 3 days) less than 70 mg/dL and 54 mg/dL

Time Frame

3 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark Molitch, MD

Organizational Affiliation

Northwestern University Feinberg School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern University Feinberg School of Medicine

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

No

Citations:

PubMed Identifier

22784834

Citation

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.

Results Reference

result

PubMed Identifier

26474657

Citation

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.

Results Reference

result

PubMed Identifier

27995731

Citation

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.

Results Reference

result

PubMed Identifier

19885233

Citation

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.

Results Reference

result

PubMed Identifier

21387555

Citation

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.

Results Reference

result

Hyperglycemia Steroid-induced, Insulin Resistance, Diabetes

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial