PTHG: Insulin Therapy for Post-transplant Glucocorticoid Induced Hyperglycemia
Study Details
Study Description
Brief Summary
No consensus guidelines exist for management of post-transplant glucocorticoid induced hyperglycemia, but most published reviews recommend insulin as first line therapy. A variety of insulin regimens have been proposed, including mealtime short-acting regular or analog insulin, once daily neutral protamine hagedorn (NPH) insulin, pre-mixed insulin, or basal insulin alone such as glargine or detemir. However, no randomized trial has ever examined different insulin regimens to determine which most effectively controls post-transplant steroid-induced hyperglycemia. Consequently, the proposed study intends to examine three commonly used insulin regimens used for managing post-transplant once-daily glucocorticoid-induced hyperglycemia to determine which is most effective:
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Group 1: Intermediate-acting (NPH) insulin at breakfast
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Group 2: Short-acting insulin (regular or aspart) before meals
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Group 3: Insulin glargine at breakfast
Question/Hypothesis:
Among three commonly used insulin regimens, which is most effective for managing post-transplant once-daily glucocorticoid-induced hyperglycemia?
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Neutral protamine hagedorn (NPH) insulin Drug: Neutral protamine hagedorn (NPH) insulin Other Names: Humulin N, Novolin N Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before breakfast; Duration: 12 hours; for duration subjects are concurrently administered once-daily glucocorticoid. |
Drug: Neutral protamine hagedorn (NPH) insulin
Other Names:
|
| Experimental: Regular or Aspart insulin Drug: Regular human insulin or Insulin Aspart Other Names: Humulin R, Novolin R, Novolog, NovoRapid Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before meals; Duration: 2 hours (Aspart) or 6 hours (Regular); for duration subjects are concurrently administered once-daily glucocorticoid. |
Drug: Regular human insulin or Insulin Aspart
Other Names:
|
| Experimental: Insulin glargine Drug: Insulin glargine Other Names: Lantus Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before breakfast; Duration: 24 hours; for duration subjects are concurrently administered once-daily glucocorticoid. |
Drug: Insulin glargine
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Blood glucose - inpatient [Time (days) from enrollment to described treatment range, an expected average of 7 days]
Mean time from baseline to achieve at least 80% of pre-meal capillary blood glucose values within 5.0 - 7.8 mmol/L over a 48 hour period during hospitalization
Secondary Outcome Measures
- Blood glucose - inpatient [Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days]
Mean inpatient capillary blood glucose (mmol/L) from enrollment to discharge from hospital
- Post prandial blood glucose - inpatient [Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days]
Mean inpatient two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to discharge from hospital
- Length of inpatient hospital stay [Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days]
Length of stay in hospital (days) from enrollment to discharge from hospital
- Blood glucose [Enrollment to 3 months]
Mean fasting blood glucose (mmol/L) from enrollment to 3 months
- Hemoglobin A1C [Enrollment to 3 months]
Mean hemoglobin A1C (%) from enrollment to 3 months
- Post prandial blood glucose [Enrollment to 3 months]
Mean two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to 3 months
- Hypoglycemic episodes [Enrollment to 3 months]
Hypoglycemic episodes defined as: (1) Mild - any measured CBG 3.0-4.0 mmol/L; (2) Severe - any episode of hypoglycemia with a measured CBG < 3.0 mmol/L, OR which the subject is not able to recognize and treat without the direct (substantial) intervention of a professional caregiver, nurse or physician (e.g. intravenous dextrose or intramuscular glucagon)
- Glycemic treatment failure [Enrollment to 3 months]
Hypoglycemic treatment failure: subject experiences ≥3 hypoglycemic episodes (≤ 4.0 mmol/L) over any 5 day period or a single severe hypoglycemic event (as previously defined), they will be withdrawn from study and managed at discretion of attending physician, or hospital endocrine consult service. Hyperglycemic treatment failure: Severe hyperglycemia defined as CBG >20 mmol/L. If subject experiences ≥3 severe hyperglycemic measures over the course of 48 hours they will be withdrawn from the study and managed at discretion of attending physician, or hospital endocrine consult service.
- Cardiovascular events [Enrollment to 3 months]
New cardiovascular events defined as: myocardial infarction, new or worsened congestive heart failure, stroke, and cardiac arrhythmia.
- Post-transplant infections or new antibiotic use [Enrollment to 3 months]
Post-transplant infections or new antibiotic use from enrollment to 3 months.
- Transplant graft failure [Enrollment to 3 months]
Transplant graft failure (as specified by subject's medical transplant physician) from enrollment to 3 months.
- New acute renal failure [Enrollment to 3 months]
New acute renal failure is defined according to Acute Kidney Network Guidelines: rapid time course and decreased kidney function according to an absolute Creatinine (Cr) rise greater than 26 μmol/L, greater than 2-fold increase in serum Cr from baseline, or urine output less than 0.5 mL/kg/hr for greater than 6 hours
- Mortality [Enrollment to 3 months]
Overall subject mortality from baseline to 3 months.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Have undergone bone marrow, liver, lung, or renal transplant.
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Be using once daily oral glucocorticoid therapy (total daily dose of Prednisone ≥10 mg, Hydrocortisone ≥40 mg, Dexamethasone ≥1.5 mg) administered in the morning and expected to continue for at least 2 weeks.
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Have pre-existing or newly diagnosed diabetes mellitus established by any of the criteria listed below:
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Fasting plasma glucose ≥7.0 mmol/L (repeated x 1)
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Any plasma glucose ≥11.0 mmol/L
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Have at least three pre-meal inpatient capillary blood glucose (CBG) readings ≥ 7.8 mmol/L
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Be eating meals by mouth
Exclusion Criteria:
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Heart, Pancreas, Islet cell transplant recipients
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Previous use of Basal-Bolus or Pre-Mixed Insulin regimen
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Diabetes mellitus type I
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NPO (not eating meals by mouth)
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Receiving enteral (tube feeds) or parenteral (TPN) nutrition
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vancouver General Hospital - Jim Pattison Pavilion | Vancouver | British Columbia | Canada | V5Z 1M9 |
Sponsors and Collaborators
- Vancouver General Hospital
Investigators
- Principal Investigator: Breay W Paty, MD, FRCPC, Vancouver General Hospital, University of British Columbia
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Griffith ML, Jagasia M, Jagasia SM. Diabetes mellitus after hematopoietic stem cell transplantation. Endocr Pract. 2010 Jul-Aug;16(4):699-706. doi: 10.4158/EP10027.RA. Review.
- Lane JT, Dagogo-Jack S. Approach to the patient with new-onset diabetes after transplant (NODAT). J Clin Endocrinol Metab. 2011 Nov;96(11):3289-97. doi: 10.1210/jc.2011-0657.
- Lansang MC, Hustak LK. Glucocorticoid-induced diabetes and adrenal suppression: how to detect and manage them. Cleve Clin J Med. 2011 Nov;78(11):748-56. doi: 10.3949/ccjm.78a.10180. Review.
- Sarno G, Muscogiuri G, De Rosa P. New-onset diabetes after kidney transplantation: prevalence, risk factors, and management. Transplantation. 2012 Jun 27;93(12):1189-95. doi: 10.1097/TP.0b013e31824db97d. Review.
- Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, Seley JJ, Van den Berghe G; Endocrine Society. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012 Jan;97(1):16-38. doi: 10.1210/jc.2011-2098.
- PTHG.VGH.UBC