Insulin Therapy for Post-transplant Glucocorticoid Induced Hyperglycemia (PTHG)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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?
| Condition | Intervention | Phase |
|---|---|---|
|
Post-Transplant Glucocorticoid Induced Diabetes |
Drug: Neutral protamine hagedorn (NPH) insulin Drug: Regular human insulin or Insulin Aspart Drug: Insulin glargine |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Insulin Therapy for Post-transplant Glucocorticoid Induced Hyperglycemia |
- Blood glucose - inpatient [ Time Frame: Time (days) from enrollment to described treatment range, an expected average of 7 days ] [ Designated as safety issue: No ]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
- Blood glucose - inpatient [ Time Frame: Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days ] [ Designated as safety issue: No ]Mean inpatient capillary blood glucose (mmol/L) from enrollment to discharge from hospital
- Post prandial blood glucose - inpatient [ Time Frame: Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days ] [ Designated as safety issue: No ]Mean inpatient two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to discharge from hospital
- Length of inpatient hospital stay [ Time Frame: Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days ] [ Designated as safety issue: No ]Length of stay in hospital (days) from enrollment to discharge from hospital
- Blood glucose [ Time Frame: Enrollment to 3 months ] [ Designated as safety issue: No ]Mean fasting blood glucose (mmol/L) from enrollment to 3 months
- Hemoglobin A1C [ Time Frame: Enrollment to 3 months ] [ Designated as safety issue: No ]Mean hemoglobin A1C (%) from enrollment to 3 months
- Post prandial blood glucose [ Time Frame: Enrollment to 3 months ] [ Designated as safety issue: No ]Mean two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to 3 months
- Hypoglycemic episodes [ Time Frame: Enrollment to 3 months ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Enrollment to 3 months ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Enrollment to 3 months ] [ Designated as safety issue: No ]New cardiovascular events defined as: myocardial infarction, new or worsened congestive heart failure, stroke, and cardiac arrhythmia.
- Post-transplant infections or new antibiotic use [ Time Frame: Enrollment to 3 months ] [ Designated as safety issue: No ]Post-transplant infections or new antibiotic use from enrollment to 3 months.
- Transplant graft failure [ Time Frame: Enrollment to 3 months ] [ Designated as safety issue: No ]Transplant graft failure (as specified by subject's medical transplant physician) from enrollment to 3 months.
- New acute renal failure [ Time Frame: Enrollment to 3 months ] [ Designated as safety issue: No ]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 [ Time Frame: Enrollment to 3 months ] [ Designated as safety issue: No ]Overall subject mortality from baseline to 3 months.
| Estimated Enrollment: | 120 |
| Study Start Date: | August 2012 |
| Estimated Study Completion Date: | June 2013 |
| Estimated Primary Completion Date: | April 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 Name: Humulin N, Novolin N
|
|
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 Name: Lantus
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Have undergone bone marrow, liver, lung, or renal transplant.
- 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.
Have pre-existing or newly diagnosed diabetes mellitus established by any of the criteria listed below:
- Fasting plasma glucose ≥7.0 mmol/L (repeated x 1)
- Any plasma glucose ≥11.0 mmol/L
- Have at least three pre-meal inpatient capillary blood glucose (CBG) readings ≥ 7.8 mmol/L
- Be eating meals by mouth
Exclusion Criteria:
- Heart, Pancreas, Islet cell transplant recipients
- Previous use of Basal-Bolus or Pre-Mixed Insulin regimen
- Diabetes mellitus type I
- NPO (not eating meals by mouth)
- Receiving enteral (tube feeds) or parenteral (TPN) nutrition
Contacts and Locations| Contact: Breay W Paty, MD, FRCPC | 604-875-5990 | breay.paty@vch.ca |
| Contact: David E Harris, MD, FRCPC | 778-995-5414 | deharris@interchange.ubc.ca |
| Canada, British Columbia | |
| Vancouver General Hospital - Jim Pattison Pavilion | Recruiting |
| Vancouver, British Columbia, Canada, V5Z 1M9 | |
| Contact: Breay W Paty, MD, FRCPC 604-875-5990 breay.paty@vch.ca | |
| Contact: David E Harris, MD, FRCPC 778-995-5414 deharris@interchange.ubc.ca | |
| Principal Investigator: Breay W Paty, MD, FRCPC | |
| Principal Investigator: | Breay W Paty, MD, FRCPC | Vancouver General Hospital, University of British Columbia |
More Information
Additional Information:
Publications:
| Responsible Party: | David E. Harris, MD, MD, FRCPC, Clinical Endocrinology Fellow, University of British Columbia, Vancouver General Hospital |
| ClinicalTrials.gov Identifier: | NCT01648218 History of Changes |
| Other Study ID Numbers: | PTHG.VGH.UBC |
| Study First Received: | July 12, 2012 |
| Last Updated: | October 17, 2012 |
| Health Authority: | Canada: Health Canada Canada: Ethics Review Committee |
Keywords provided by Vancouver General Hospital:
|
glucocorticoid diabetes mellitus post-transplant insulin |
Additional relevant MeSH terms:
|
Diabetes Mellitus Hyperglycemia Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Glucocorticoids Insulin aspart Glargine Insulin Insulin, Long-Acting Protamines |
Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Hypoglycemic Agents Heparin Antagonists Molecular Mechanisms of Pharmacological Action Coagulants Hematologic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013