Hyperglycemia Steroid-inducedPhase 4NCT03511521
Use of NPH Versus Basal Bolus Insulin for Steroid Induced Hyperglycemia
A Phase 4 study testing NPH Insulin, glargine and Insulin Aspart in people with Hyperglycemia Steroid-induced and Insulin Resistance, Diabetes, run by Northwestern University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperglycemia Steroid-induced, Insulin Resistance, Diabetes
- What is being tested?
- NPH Insulin, glargine and Insulin Aspart
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Mar 2018to 15 Aug 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
About this study
Official title: Use of Neutral Protamine Hagedorn (NPH) Versus Basal Bolus Insulin for Steroid Induced Hyperglycemia
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.
Read the 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.
- Being tested
- NPH Insulin, glargine, Insulin Aspart
- Keywords
- steroid, prednisone, methylprednisolone, hyperglycemia, insulin, hypoglycemia
- Medical subject headings
- Insulin Resistance, Diabetes Mellitus, Hyperglycemia, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NPH InsulinDrug
Also called Humulin N, Novolin N
Intermediate acting insulin
glargineDrug
Also called Lantus, Basaglar
basal insulin
Insulin AspartDrug
Also called Novolog
prandial insulin
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: glargine; Drug: Insulin Aspart |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glycemic Control
mean of 4 glucose levels per day (premeal and bedtime) for each group for first 3 days after intervention
Measured: 3 days
Secondary outcomes (2)
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
Measured: 3 days
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
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2018
- Study start27 Mar 2018
- Primary completion15 Aug 2019
- Study completion15 Aug 2019
Why it stopped: Unable to recruit sufficient number of patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hyperglycemia Steroid-inducedStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mark E Molitch, Northwestern University
- Investigators
- Mark Molitch, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03511521
- Sponsor's protocol ID
- STU00207079
- Status last verified
- Aug 2020
- First submitted
- 18 Apr 2018
- Last updated
- 11 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 22784834Ruiz 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.
PubMed 26474657Radhakutty 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.
PubMed 27995731Bevier 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.
PubMed 19885233Seggelke 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.
PubMed 21387555
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Neutral Protamine Hagedorn (NPH) Versus Basal Bolus Insulin for Steroid Induced Hyperglycemia
- ClinicalTrials.gov ID
- NCT03511521
- Acronym / sponsor ID
- STU00207079
- Keywords
- steroid, prednisone, methylprednisolone, hyperglycemia, insulin, hypoglycemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to recruit sufficient number of patients
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- 27 Mar 2018 (actual)
- Primary completion
- 15 Aug 2019 (actual)
- Study completion
- 15 Aug 2019 (actual)
- First posted
- 27 Apr 2018 (actual)
- Results
- Posted 11 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| NPH Insulin | Experimental | Drug: NPH Insulin, Drug: glargine, Drug: Insulin AspartNPH 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/Bolus Insulin | Active comparator | Drug: glargine, Drug: Insulin AspartBasal 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NPH InsulinAlso: Humulin N, Novolin NIntermediate acting insulin | Drug | NPH Insulin |
| glargineAlso: Lantus, Basaglarbasal insulin | Drug | Basal/Bolus Insulin, NPH Insulin |
| Insulin AspartAlso: Novologprandial insulin | Drug | Basal/Bolus Insulin, NPH Insulin |
Primary outcome
Glycemic Control
Time frame: 3 days
mean of 4 glucose levels per day (premeal and bedtime) for each group for first 3 days after intervention
2 secondary outcomes
Percentage of Glucose Values Within Therapeutic Range
Time frame: 3 days
Percentage of Glucose Values Within the Hypoglycemic Range
Time frame: 3 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22784834Dhital 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 publication: PubMed 26474657Ruiz 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 publication: PubMed 27995731Radhakutty 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 publication: PubMed 19885233Bevier 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 publication: PubMed 21387555Seggelke 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.
- Individual participant dataSharing planned: No
Related trials for Hyperglycemia Steroid-induced
Active, not recruitingPhase 1/2
Pre-emptive Insulin to Prevent High Glucose After a Knee Steroid Injection in Adults With Type 2 Diabetes
Diabetes Mellitus, Type 2, Hyperglycemia Due to Type 2 Diabetes Mellitus
Not yet recruiting
CGM-guided Patch Pump vs Basal-Bolus Injection for Steroid-Induced Hyperglycemia in Sudden Sensorineural Hearing Loss: SHIP Trial
Sudden Sensorineural Hearing Loss (SSNHL), Prediabetes / Type 2 Diabetes
RecruitingObservational study
Metabolic Control in Anesthesia and Surgery
Anesthesia, Continuous Glucose Monitoring
Enrolling by invitationObservational study
Predictive Factors and Monitoring Strategies in Steroid-Induced Diabetes
Steroid-Induced Diabetes, Diabete Type 2
Enrolling by invitationPhase 4
Evaluation of the Efficacy and Safety of GLP-1 Receptor Agonist Therapy In Steroid-Induced Diabetes
Steroid-Induced Diabetes, Steroid-Induced Hyperglycemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Molitch, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing NPH Insulin, glargine and Insulin Aspart in people with Hyperglycemia Steroid-induced and Insulin Resistance, Diabetes, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glycemic Control (time frame: 3 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03511521, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2020.