Pharmacodynamics of Nasal and Buccal Midazolam Using EEG (nMDZ-EEG)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Upsher-Smith Laboratories
Information provided by (Responsible Party):
Bin Tu, Columbia University
ClinicalTrials.gov Identifier:
NCT01316445
First received: March 15, 2011
Last updated: November 15, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Epilepsy
Drug: intranasal midazolam hydrochloride
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 25
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)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • adults undergoing extracranial EEG in an Epilepsy Monitoring Unit
  • adults undergoing intracranial EEG in an Epilepsy Monitoring Unit
  • adults with chronically implanted intracranial neurostimulators with the capacity for continuous intracranial EEG monitoring

Exclusion Criteria:

  • any patient on additional sedative medications (narcotics, other central nervous system depressants)
  • any patient with documented sensitivity or adverse reaction to any benzodiazepine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01316445

Locations
United States, New York
Columbia University Medical Center, Milstein Hospital
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Upsher-Smith Laboratories
Investigators
Principal Investigator: Derek Chong, MD Columbia University
  More Information

Additional Information:
Publications:
Responsible Party: Bin Tu, Associate Research Scientist, Columbia University
ClinicalTrials.gov Identifier: NCT01316445     History of Changes
Other Study ID Numbers: AAAF3704
Study First Received: March 15, 2011
Last Updated: November 15, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Electroencephalography
Benzodiazepines
Midazolam

Additional relevant MeSH terms:
Midazolam
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014