Pharmacodynamics of Nasal and Buccal Midazolam Using EEG (nMDZ-EEG)
Approximately 3 million individuals suffer from epilepsy in America alone and about 200,000 new cases of epilepsy in America are diagnosed each year (Epilepsy Foundation, 2005). Epilepsy can be defined as a condition in which a person has recurrent, unprovoked seizures. Prolonged or back-to-back repetitive seizures, known as "acute repetitive seizures" (ARS), are medical emergencies. ARS can occur unexpectedly, a circumstance for which quick and efficient antiepileptic drugs are needed for household and prehospital use. Currently, benzodiazepines are the antiepileptic drug of choice when dealing with ARS because they are proven to be efficient and take little time to work. Benzodiazepines can be administered by mouth, by vein via a needle (intravenously; IV), rectally, between the cheek and gum (buccally), or in the nose (intranasally; IN). The nasal formulation is not yet FDA-approved. The rectal treatment route has been commonly used for acute seizure treatment in past years, but recent studies propose that the nasal route for benzodiazepines may be better overall for home treatment and easier to administer (see Wermeling, 2009). For many "out of hospital" situations, nasal benzodiazepines can be more convenient and more comfortable than rectal treatment. In addition to the above benefits, nasal benzodiazepines are rapidly absorbed by the blood vessels in the nose and the time of drug administration and cessation of seizures may thus be reduced using nasal routes. This study sets out to characterize how fast buccal and nasal treatments begin to work on the brain by monitoring brain waves during administration of the drug, and to determine whether nasal or buccal administration is best.
|Study Design:||Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Comparing the Pharmacodynamics of Nasal and Buccal Midazolam Using EEG|
- 25% increase in total beta power for at least 1 minute at 10-30Hz [ Time Frame: for 30 mins after administration of drug ] [ Designated as safety issue: No ]Quantitative and qualitative visual EEG analysis for benzodiazepine-induced beta activity, total power of ~10-30 Hz activity
- beta activity at 10-12 Hz [ Time Frame: for 30 minutes after drug administration ] [ Designated as safety issue: No ]Qualitative visual and quantitative EEG analysis for benzodiazepine-induced beta activity at bands of 10-12 Hz
- beta activity at 30-40Hz [ Time Frame: for 30 minutes after drug administration ] [ Designated as safety issue: No ]Qualitative visual and quantitative EEG analysis for benzodiazepine-induced beta activity at bands of 30-40Hz.
- sedation [ Time Frame: for 30 minues after drug administration ] [ Designated as safety issue: Yes ]Subject perception of sedation will be evaluated using yes or no type questions, evaluation questions using a visual analogue scale (from 1 to 10) and open response questions.
- pain/discomfort [ Time Frame: for 30 minutes after drug administration ] [ Designated as safety issue: No ]Subject perception of discomfort will be evaluated using yes or no type questions, evaluation questions on a visual analogue scale (from 1 to 10), and open-response questions.
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||July 2013|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
|Experimental: nasal Midazolam||
Drug: intranasal midazolam hydrochloride
Intranasal and buccal administration of the standard IV formulation of midazolam (5mg/mL), administered via a metered dose sprayer at 0.1mL/spray (i.e. 0.5mg/spray). Administration will be via three sprays in each nostril (for nasal) or three sprays between the cheek and the gum per side (for buccal).
Other Name: Versed
Past out-of-hospital treatments for acute epileptic seizures have met with limited effectiveness, convenience, speed, and safety. The only FDA-approved treatment for acute repetitive seizures must be given rectally, but nasal or buccal midazolam have been shown to be at least as effective. The purpose of this study is to characterize the time to effect on brain activity of intranasal (or nasal) midazolam and compare it with buccal midazolam. This research will recruit patients with epilepsy who are undergoing EEG recordings for clinical purposes, including those with intracranial EEG. EEG will be evaluated during administration of buccal or nasal midazolam for augmentation of beta waves signifying action of midazolam on the brain, and the time to effect will be compared between buccal and nasal formulations. Subjects will be given a brief survey after the administration to evaluate sedation, discomfort and other adverse effects of the medication. This study will help characterize the action of nasal and buccal benzodiazepines and to determine the most effective method of administration.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01316445
|United States, New York|
|Columbia University Medical Center, Milstein Hospital|
|New York, New York, United States, 10032|
|Principal Investigator:||Derek Chong, MD||Columbia University|