Acute Effect of Lorazepam on Brain Activity Measured by Magnetoencephalograpy (MEG) and Electroencephalography (EEG)

Acute Effect of Four Doses of Lorazepam on Brain Activity Measured by MEG, EEG and the Synchronous Neural Interaction™ Test

This placebo-controlled crossover study is intended to measure the effect of four doses of lorazepam on brain activity measured by magnetoencephalography (MEG) and electroencephalography (EEG). This study will conduct MEG and EEG scans as well as simple cognition testing on 16 healthy male volunteers. On each of five study days subjects will be randomized to receive either 0.2, 0.5, 1.0 or 2.0 mg lorazepam or placebo. Brain activity will be measured by MEG and EEG in each subject a total of 4 times each study day: prior to medication administration and 2, 4, and 6 hours after medication administration. Blood samples to determine medication levels and cognition testing will be performed at pre-medication baseline and immediately after each post-medication scan time. Data will be analyzed to identify changes in brain activity compared to baseline and placebo administration using both standard approaches and the Orasi Synchronous Neural Interaction® (SNI) test. This study will test the hypothesis that dose-response changes in brain functional activity can be accurately measured by MEG/EEG in healthy volunteer subjects after single, acute doses of lorazepam.

Study Overview

• Status: Unknown
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Lorazepam; Drug: Lorazepam; Drug: Lorazepam; Drug: Lorazepam; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christina Kay, MA; Phone Number: 847-981-3570; Email: christina.kay@abbhh.net
• Study Contact Backup: Name: Donnell Carmichael, PsyD; Phone Number: 847-981-5771; Email: donnell.carmichael@abbhh.net

Study Locations

• United States
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Recruiting
      • Alexian Brothers Neurosciences Institute
      • Contact: Christina Kay, MA; Phone Number: 847-981-3570; Email: christina.kay@abbhh.net
      • Contact: Donnell Carmichael, PsyD; Phone Number: 847-981-5771; Email: donnell.carmichael@abbhh.net
      • Principal Investigator: Concetta Forchetti, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subject is male between 18 and 35 years of age at the time of screening.
• Subject understands the study procedures and agrees to participate in the study by giving written informed consent.
• Subject is a non-smoker.
• Subject is judged to be in good health based on medical history and brief physical examination and electrocardiogram.
• Subject has normal or corrected to normal visual and auditory acuity.
• Subject agrees to refrain from caffeine 24 hours prior to and then throughout each Study Day.
• Subject agrees to refrain from using alcohol for 48 hours prior to and then throughout each Study Day.

Exclusion Criteria:

• Subject has a diagnosis of a significant neurological condition including Alzheimer's disease, Parkinson's disease, vascular dementia, Lewy body dementia or frontal temporal dementia, human immunodeficiency virus, multiple sclerosis, or severe traumatic brain injury.
• Subject has a history of primary psychotic disorder (e.g. schizophrenia, schizoaffective disorder, delusional disorder) or bipolar disorder.
• Subject has a history of seizures, epilepsy, stroke, peripheral neuropathy, head trauma with persistent post-concussive symptoms, ADHD, dyslexia or other clinically significant neurological disease or cognitive impairment.
• Subject has a lifetime or current history of alcohol or substance abuse/dependence.
• Subject has a history of multiple or severe allergies, or has had an anaphylactic reaction or intolerability to prescription or non-prescription drugs. This includes a documented or subject-verified allergy.
• Subject had an MRI 2 weeks prior to Study Day 2.
• Subject has metal braces or pacemaker that may interfere with the MEG scan.
• Subject is unable to complete the MEG scan procedure.
• The investigator has any concern regarding the safe participation of a subject in the study, or if for any other reason the investigator considers the subject inappropriate for study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lorazepam 0.2 mg; All subjects receive lorazepam 0.2 mg in this crossover design.	Drug: Lorazepam; Oral capsule, 0.2 mg, single acute dose; Drug: Lorazepam; oral capsule, 0.5 mg, single acute dose; Drug: Lorazepam; oral capsule, 1.0 mg, single acute dose; Drug: Lorazepam; oral capsule, 2.0 mg, single acute dose
Experimental: Lorazepam, 0.5 mg; All subjects receive lorazepam 0.5 mg in this crossover design.	Drug: Lorazepam; Oral capsule, 0.2 mg, single acute dose; Drug: Lorazepam; oral capsule, 0.5 mg, single acute dose; Drug: Lorazepam; oral capsule, 1.0 mg, single acute dose; Drug: Lorazepam; oral capsule, 2.0 mg, single acute dose
Experimental: Lorazepam, 1.0 mg; All subjects receive lorazepam 1.0 mg in this crossover design.	Drug: Lorazepam; Oral capsule, 0.2 mg, single acute dose; Drug: Lorazepam; oral capsule, 0.5 mg, single acute dose; Drug: Lorazepam; oral capsule, 1.0 mg, single acute dose; Drug: Lorazepam; oral capsule, 2.0 mg, single acute dose
Experimental: Lorazepam, 2.0 mg; All subjects receive lorazepam 2.0 mg in this crossover design	Drug: Lorazepam; Oral capsule, 0.2 mg, single acute dose; Drug: Lorazepam; oral capsule, 0.5 mg, single acute dose; Drug: Lorazepam; oral capsule, 1.0 mg, single acute dose; Drug: Lorazepam; oral capsule, 2.0 mg, single acute dose
Placebo Comparator: Sugar pill; All subjects receive a sugar pill in this crossover design.	Drug: Placebo; oral capsule, single acute dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlated Brain Activity using MEG and SNI analysis	The identification and characterization of a pattern of synchronous brain activity that is specifically altered by administration of ascending doses of lorazepam compared to pre-medication baseline and placebo	2 hours after dosing with lorazepam

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlated Brain Activity using MEG and standard analyses	Standard frequency-domain analysis of the MEG data to identify and quantify medication-induced changes in signal power in particular frequency bands associated with brain functional activity	2 hours after dosing with lorazepam

Collaborators and Investigators

• Sponsor: Orasi Medical, Inc.
• Investigators: Principal Investigator: Concetta Forchetti, MD, PhD, Alexian Brothers Neurosciences Institute

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Anticipated): April 1, 2011
• Study Completion (Anticipated): April 1, 2011

Study Registration Dates

• First Submitted: January 5, 2011
• First Submitted That Met QC Criteria: January 7, 2011
• First Posted (Estimate): January 10, 2011

Study Record Updates

• Last Update Posted (Estimate): January 10, 2011
• Last Update Submitted That Met QC Criteria: January 7, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Lorazepam
• Other Study ID Numbers: ADE-LDR 10-02