Intravenous Exenatide in Patients With Acute Brain Injury

Intravenous Exenatide Infusion in Critically Ill Patients With Acute Brain Injury

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

Study Overview

• Status: Completed
• Conditions: Brain Injuries
• Intervention / Treatment: Drug: Exenatide

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina; UNC Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exenatide	Drug: Exenatide; 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: AstraZeneca; Medtronic
• Investigators: Principal Investigator: Nicole R. Pinelli, PharmD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: February 6, 2014
• First Submitted That Met QC Criteria: February 6, 2014
• First Posted (Estimate): February 10, 2014

Study Record Updates

• Last Update Posted (Actual): July 12, 2018
• Last Update Submitted That Met QC Criteria: July 11, 2018
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: 13-1391; Astra Zeneca Pharmaceuticals (Other Grant/Funding Number: D5550L00025/ISSEXEN0038); Medtronic MiniMed, Inc (Other Grant/Funding Number: NERP14-008)