Intravenous Exenatide in Patients With Acute Brain Injury

Phase 4

Completed

Conditions: Brain Injuries

Interventions: Drug: Exenatide

Registration Number: NCT02058940

Lead Sponsor: University of North Carolina, Chapel Hill

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 8

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Exenatide	Exenatide	-

Primary Outcome Measures

Name	Time	Method
Percentage of Critically Ill Patients With Acute Brain Injury Achieving Pre-specified Feasibility Criteria	Over 48 hours from infusion initiation	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.

Secondary Outcome Measures

Name	Time	Method
Median Intensive Care Unit Length of Stay	From enrollment to 30 days post study drug discontinuation	Defined as the number of days admitted to the Intensive Care Unit
Exenatide Elimination Rate Constant After Discontinuation of Infusion	24 hours
Median Insulin Use	Over 48 hours from infusion initiation	Calculated from number of insulin units administered over 48 hours starting at infusion initiation
Percentage of Patients Requiring Rescue Insulin Infusion Protocol	Over 48 hours from infusion initiation	Defined as the percentage of patients requiring an insulin infusion to control glucose concentrations during exenatide treatment
Percentage of Hypoglycemic Episodes (<80 mg/dL)	Over 48 hours from infusion initiation	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.
Median Daily Cerebral Perfusion Pressure	Over 48 hours from infusion initiation	Calculated from hourly measurements starting at infusion initiation over 48 hours
Percentage of Hypotensive Episodes (SBP<100 mmHg)	Over 48 hours from infusion initiation	Defined as the number of hypotensive episodes (SBP\<100 mmHg)for all patients/total number of blood pressure measurements collected for all patients.
Median Hospital Length of Stay	From enrollment to 30 days post study drug discontinuation	Defined as the number of days admitted to the hospital
Percentage of Patients With >1 Episode of Hypotensive Episode (SBP<100 mmHg)	Over 48 hours from infusion initiation	Calculated from blood pressure measurements starting at infusion initiation over 48 hours
Median Glucose Concentration During Exenatide Infusion	Over 48 hours from infusion initiation	Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
Median Time to Reach Glucose Measurements Within Goal Range (110-180 mg/dL)	Over 48 hours from infusion initiation	Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
Exenatide Area Under the Concentration-time Curve After Discontinuation of Infusion	24 hours
Percentage of Glucose Measurements Within Goal Range	Over 48 hours from infusion initiation	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.
Glycemic Variability	Over 48 hours from infusion initiation	Glycemic variability is defined as the standard deviation of glucose calculated from hourly glucose measurements starting at infusion initiation over 48 hours
Percentage of Patients With >1 Episode of Hypoglycemia (<80 mg/dL)	Over 48 hours from infusion initiation	Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
Median Daily Intracranial Pressure	Over 48 hours from infusion initiation	Calculated from hourly measurements starting at infusion initiation over 48 hours
Percentage of Patients Experiencing Metabolic Crisis	Over 48 hours from infusion initiation	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
Correlation of Exenatide Concentrations With Creatinine Clearance	Over 48 hours from infusion initiation	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.