Post-Transplant Glucocorticoid Induced Diabetes Clinical Trial
— PTHGOfficial title:
Insulin Therapy for Post-transplant Glucocorticoid Induced Hyperglycemia
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:
- Group 1: Intermediate-acting (NPH) insulin at breakfast
- Group 2: Short-acting insulin (regular or aspart) before meals
- 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?
| Status | Terminated |
| Enrollment | 5 |
| Est. completion date | June 2013 |
| Est. primary completion date | April 2013 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. Have undergone bone marrow, liver, lung, or renal transplant. 2. 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. 3. Have pre-existing or newly diagnosed diabetes mellitus established by any of the criteria listed below: 1. Fasting plasma glucose =7.0 mmol/L (repeated x 1) 2. Any plasma glucose =11.0 mmol/L 4. Have at least three pre-meal inpatient capillary blood glucose (CBG) readings = 7.8 mmol/L 5. Be eating meals by mouth Exclusion Criteria: 1. Heart, Pancreas, Islet cell transplant recipients 2. Previous use of Basal-Bolus or Pre-Mixed Insulin regimen 3. Diabetes mellitus type I 4. NPO (not eating meals by mouth) 5. Receiving enteral (tube feeds) or parenteral (TPN) nutrition |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Canada | Vancouver General Hospital - Jim Pattison Pavilion | Vancouver | British Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Vancouver General Hospital |
Canada,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Blood glucose - inpatient | 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 | Time (days) from enrollment to described treatment range, an expected average of 7 days | No |
| Secondary | Blood glucose - inpatient | Mean inpatient capillary blood glucose (mmol/L) from enrollment to discharge from hospital | Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days | No |
| Secondary | Post prandial blood glucose - inpatient | Mean inpatient two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to discharge from hospital | Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days | No |
| Secondary | Length of inpatient hospital stay | Length of stay in hospital (days) from enrollment to discharge from hospital | Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days | No |
| Secondary | Blood glucose | Mean fasting blood glucose (mmol/L) from enrollment to 3 months | Enrollment to 3 months | No |
| Secondary | Hemoglobin A1C | Mean hemoglobin A1C (%) from enrollment to 3 months | Enrollment to 3 months | No |
| Secondary | Post prandial blood glucose | Mean two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to 3 months | Enrollment to 3 months | No |
| Secondary | Hypoglycemic episodes | 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) |
Enrollment to 3 months | Yes |
| Secondary | Glycemic treatment failure | 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. |
Enrollment to 3 months | Yes |
| Secondary | Cardiovascular events | New cardiovascular events defined as: myocardial infarction, new or worsened congestive heart failure, stroke, and cardiac arrhythmia. | Enrollment to 3 months | No |
| Secondary | Post-transplant infections or new antibiotic use | Post-transplant infections or new antibiotic use from enrollment to 3 months. | Enrollment to 3 months | No |
| Secondary | Transplant graft failure | Transplant graft failure (as specified by subject's medical transplant physician) from enrollment to 3 months. | Enrollment to 3 months | No |
| Secondary | New acute renal failure | 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 | Enrollment to 3 months | No |
| Secondary | Mortality | Overall subject mortality from baseline to 3 months. | Enrollment to 3 months | No |