Intravenous Exenatide in Patients With Acute Brain Injury

Study Overview
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Brief Summary
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The purpose of this study is to assess the feasibility of exenatide infusion for the treatment of high blood sugars following acute brain injury.

Official Title
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Intravenous Exenatide Infusion in Critically Ill Patients With Acute Brain Injury

Conditions
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Brain Injuries

Intervention / Treatment
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* Drug: Exenatide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥18 years Acute brain injury resulting in admission to the Neurosciences Intensive Care Unit for an anticipated length of stay >48 hours Two Blood glucose concentrations > 150 mg/dL and ≤300 mg/dL Informed consent obtained via proxy Exclusion Criteria: Pregnant (verified by urine or serum pregnancy test within 24 hours of initiation of infusion) or lactating females Type 1 diabetes mellitus History of pancreatitis or risk factors for acute pancreatitis (i.e ethanol abuse, gall stones) Renal insufficiency defined as creatinine clearance (CrCL) < 45 mL/min Known history of gastroparesis History of surgery on stomach, esophagus or duodenum Diabetic Ketoacidosis or Hyperosmolar Hyperglycemic Nonketotic Syndrome Concurrent steroid use or planned post-operative steroid use History of organ transplantation Brain death or suspected imminent brain death within the next 72 hours Refractory intracranial hypertension defined as intracranial pressure (ICP) > 25 mmHg for greater than 15 minutes and refractory to medical intervention Currently enrolled in another investigational drug or device protocol Insulin infusion within 3 hours of study drug administration or confirmed long acting insulin or sulfonylurea use prior to admission within 24 hours of study drug administration Known allergy to exenatide

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide<br> | Drug: Exenatide<br>* 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Critically Ill Patients With Acute Brain Injury Achieving Pre-specified Feasibility Criteria | Feasibility is defined as the percentage of patients 1) experiencing severe hypoglycemia (<40 mg/dL); 2) achieving glucose measurements within goal (110-180 mg/dL); and 3) experiencing nausea requiring discontinuation of exenatide therapy. The pre-specified criteria for determining feasibility includes the following: 1) at least 75% of patients achieving glucose measurements within goal (110-180 mg/dL) and 2) no more than 25% of patients experiencing severe hypoglycemia (<40 mg/dL) or nausea requiring exenatide discontinuation. | Over 48 hours from infusion initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Glucose Concentration During Exenatide Infusion | Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours | Over 48 hours from infusion initiation | 
| Percentage of Glucose Measurements Within Goal Range | Percentage of glucose measurements within goal range is calculated as the number of glucose measurements within goal range (110-180 mg/dL) for all patients/total number of glucose measurements collected for all patients. | Over 48 hours from infusion initiation | 
| Median Time to Reach Glucose Measurements Within Goal Range (110-180 mg/dL) | Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours | Over 48 hours from infusion initiation | 
| Glycemic Variability | Glycemic variability is defined as the standard deviation of glucose calculated from hourly glucose measurements starting at infusion initiation over 48 hours | Over 48 hours from infusion initiation | 
| Median Insulin Use | Calculated from number of insulin units administered over 48 hours starting at infusion initiation | Over 48 hours from infusion initiation | 
| Percentage of Patients Requiring Rescue Insulin Infusion Protocol | Defined as the percentage of patients requiring an insulin infusion to control glucose concentrations during exenatide treatment | Over 48 hours from infusion initiation | 
| Percentage of Hypoglycemic Episodes (<80 mg/dL) | Percentage of hypoglycemic episodes is calculated as the total number of glucose measurements <80 mg/dL for all patients/total number of glucose measurements collected for all patients. | Over 48 hours from infusion initiation | 
| Percentage of Patients With >1 Episode of Hypoglycemia (<80 mg/dL) | Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours | Over 48 hours from infusion initiation | 
| Percentage of Patients Experiencing Metabolic Crisis | Metabolic crisis is defined as cerebral microdialysate glucose concentration <0.7 mmol/L in combination with lactate pyruvate ratio >40. Calculated from hourly microdialysis samples starting at infusion initiation over 48 hours | Over 48 hours from infusion initiation | 
| Median Daily Intracranial Pressure | Calculated from hourly measurements starting at infusion initiation over 48 hours | Over 48 hours from infusion initiation | 
| Median Daily Cerebral Perfusion Pressure | Calculated from hourly measurements starting at infusion initiation over 48 hours | Over 48 hours from infusion initiation | 
| Percentage of Hypotensive Episodes (SBP<100 mmHg) | Defined as the number of hypotensive episodes (SBP<100 mmHg)for all patients/total number of blood pressure measurements collected for all patients. | Over 48 hours from infusion initiation | 
| Percentage of Patients With >1 Episode of Hypotensive Episode (SBP<100 mmHg) | Calculated from blood pressure measurements starting at infusion initiation over 48 hours | Over 48 hours from infusion initiation | 
| Correlation of Exenatide Concentrations With Creatinine Clearance | Spearman's correlation coefficient calculated from exenatide concentrations and urine creatinine measurements collected for all patients during the study period. A correlation coefficient is a numerical measure of some type of correlation, meaning a statistical relationship between two variables. Spearman's correlation coefficient assumes values in the range from -1 to +1, where +1 indicates the strongest possible agreement and -1 the strongest possible disagreement. | Over 48 hours from infusion initiation | 
| Exenatide Elimination Rate Constant After Discontinuation of Infusion |  | 24 hours | 
| Exenatide Area Under the Concentration-time Curve After Discontinuation of Infusion |  | 24 hours | 
| Median Intensive Care Unit Length of Stay | Defined as the number of days admitted to the Intensive Care Unit | From enrollment to 30 days post study drug discontinuation | 
| Median Hospital Length of Stay | Defined as the number of days admitted to the hospital | From enrollment to 30 days post study drug discontinuation |