AzTrials
AzTrials

EpilepsyPhase 1nMDZ-EEGNCT01316445

Pharmacodynamics of Nasal and Buccal Midazolam Using EEG

A Phase 1 study testing nasal Midazolam in people with Epilepsy, run by Columbia University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Epilepsy
What is being tested?
nasal Midazolam
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
Jul 2011to Feb 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • any patient on additional sedative medications (narcotics, other central nervous system depressants)
  • any patient with documented sensitivity or adverse reaction to any benzodiazepine

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Columbia University Medical Center, Milstein Hospital

    New York, New York, 10032

Other trials in United States

About this study

Official title: Comparing the Pharmacodynamics of Nasal and Buccal Midazolam Using 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.

Read the 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.

Conditions
Epilepsy
Being tested
nasal Midazolam
Keywords
Electroencephalography, Benzodiazepines, Midazolam
Medical subject headings
Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nasal MidazolamDrug

    Also called Versed

    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).

Study groups in NCT01316445
Study groupRoleWhat they receive
nasal MidazolamExperimental3 mg of the standard IV solution of midazolam (5 mg/mL) was given via a metered-dose nasal sprayer (6 sprays × 0.1 ml/spray, or 6 × 0.5 mg/spray) divided between the two nostrils within 1-2 min. During the EEG, vital signs (blood oxygen saturation, blood pressure, pulse and respiratory rate) were monitored and a nurse and a physician were available at all times. Subjects were monitored for 2 hours after administration of midazolam to ensure adequate recovery from sedation.
Receives: Drug: nasal Midazolam

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 25% increase in total beta power for at least 1 minute at 10-30Hz

    Quantitative and qualitative visual EEG analysis for benzodiazepine-induced beta activity, total power of ~10-30 Hz activity

    Measured: for 30 mins after administration of drug

Secondary outcomes (4)

  1. beta activity at 10-12 Hz

    Qualitative visual and quantitative EEG analysis for benzodiazepine-induced beta activity at bands of 10-12 Hz

    Measured: for 30 minutes after drug administration

  2. beta activity at 30-40Hz

    Qualitative visual and quantitative EEG analysis for benzodiazepine-induced beta activity at bands of 30-40Hz.

    Measured: for 30 minutes after drug administration

  3. sedation

    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.

    Measured: for 30 minues after drug administration

  4. pain/discomfort

    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.

    Measured: for 30 minutes after drug administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Mar 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionFeb 2014
  4. Study completionFeb 2014

Why it stopped: Funding agency no longer provide support.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01316445
Sponsor's protocol ID
AAAF3704
Acronym
nMDZ-EEG
Status last verified
Feb 2015
First submitted
15 Mar 2011
Last updated
4 Feb 2015
Results posted
No
Data monitoring committee
No

Publications

  • Loftsson T, Gudmundsdottir H, Sigurjonsdottir JF, Sigurdsson HH, Sigfusson SD, Masson M, Stefansson E. Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray. Int J Pharm. 2001 Jan 5;212(1):29-40. doi: 10.1016/s0378-5173(00)00580-9.

    PubMed 11165818

  • Knoester PD, Jonker DM, Van Der Hoeven RT, Vermeij TA, Edelbroek PM, Brekelmans GJ, de Haan GJ. Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers. Br J Clin Pharmacol. 2002 May;53(5):501-7. doi: 10.1046/j.1365-2125.2002.01588.x.

    PubMed 11994056

  • Wermeling DP, Record KA, Kelly TH, Archer SM, Clinch T, Rudy AC. Pharmacokinetics and pharmacodynamics of a new intranasal midazolam formulation in healthy volunteers. Anesth Analg. 2006 Aug;103(2):344-9, table of contents. doi: 10.1213/01.ane.0000226150.90317.16.

    PubMed 16861415

  • Wermeling DP, Record KA, Archer SM, Rudy AC. A pharmacokinetic and pharmacodynamic study, in healthy volunteers, of a rapidly absorbed intranasal midazolam formulation. Epilepsy Res. 2009 Feb;83(2-3):124-32. doi: 10.1016/j.eplepsyres.2008.10.005. Epub 2008 Nov 29.

    PubMed 19046855

  • Dale O, Nilsen T, Loftsson T, Hjorth Tonnesen H, Klepstad P, Kaasa S, Holand T, Djupesland PG. Intranasal midazolam: a comparison of two delivery devices in human volunteers. J Pharm Pharmacol. 2006 Oct;58(10):1311-8. doi: 10.1211/jpp.58.10.0003.

    PubMed 17034653

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing nasal Midazolam in people with Epilepsy, run by Columbia University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Funding agency no longer provide support.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

25% increase in total beta power for at least 1 minute at 10-30Hz (time frame: for 30 mins after administration of drug). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01316445, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2015.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in