Ability of Partial Inverse Agonist, Iomazenil, to Block Ethanol Effects in Humans

Alcohol is abused commonly, but there is no remedy for alcohol intoxication. This project is looking at the substance iomazenil and its effect on alcohol intoxication and alcohol's effects on driving using a driving simulator.

Study Overview

• Status: Completed
• Conditions: Active Ethanol and Active Iomazenil; Active Ethanol and Placebo Iomazenil; Placebo Ethanol and Placebo Iomazenil; Placebo Ethanol and Active Iomazenil; Driving Under the Influence; Alcohol Impairment; Alcohol Effect
• Intervention / Treatment: Drug: Active Ethanol; Drug: Active Iomazenil; Drug: Placebo; Drug: Placebo

Detailed Description

Alcohol is abused commonly, but there is no antidote for alcohol intoxication the way naltrexone or naloxone is an antidote for opioids. A medication that has the potential to block alcohol actions in the Central Nervous System could act as a unique medication in the treatment of alcohol intoxication and alcoholism. This project is evaluating the benzodiazepine partial inverse agonist, iomazenil, as an agent that could reverse alcohol's effects on subjective intoxication, alcohol's effects on driving using a driving simulator and on measures of electrophysiology in the laboratory in healthy subjects.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males
• 21-35 years old
• Medically healthy

Exclusion Criteria:

• Under the age of 21 or greater than the age 35
• History of seizures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Ethanol and Active Iomazenil; Participants will receive in a randomized, double-blind, cross-over design, ethanol or placebo and iomazenil or placebo. Potential Randomizations: a) active ethanol and placebo iomazenil, b) active ethanol and active iomazenil, c) placebo ethanol and active iomazenil, and d) placebo ethanol and placebo iomazenil	Drug: Active Ethanol; Target BrAC of 0.1% reached over 30 minutes and then clamped to maintain this dose for an additional 60 minutes. This dose is equivalent to consuming approximately 5 drinks. Administered over a total of 90 minutes.; Drug: Active Iomazenil; Active iomazenil, administered intravenously at a dose of 3.7 ug/kg. Administered over 10 minutes, beginning 10 minutes after the start of the ethanol/placebo clamp.
Experimental: Active Ethanol and Placebo Iomazenil; Participants will receive in a randomized, double-blind, cross-over design, ethanol or placebo and iomazenil or placebo. Potential Randomizations: a) active ethanol and placebo iomazenil, b) active ethanol and active iomazenil, c) placebo ethanol and active iomazenil, and d) placebo ethanol and placebo iomazenil	Drug: Active Ethanol; Target BrAC of 0.1% reached over 30 minutes and then clamped to maintain this dose for an additional 60 minutes. This dose is equivalent to consuming approximately 5 drinks. Administered over a total of 90 minutes.; Drug: Placebo; Control: no alcohol, administered for a total of 90 minutes.; Drug: Placebo; Control: no iomazenil, administered for a total of 10 minutes
Experimental: Placebo Ethanol and Active Iomazenil; Participants will receive in a randomized, double-blind, cross-over design, ethanol or placebo and iomazenil or placebo. Potential Randomizations: a) active ethanol and placebo iomazenil, b) active ethanol and active iomazenil, c) placebo ethanol and active iomazenil, and d) placebo ethanol and placebo iomazenil	Drug: Active Iomazenil; Active iomazenil, administered intravenously at a dose of 3.7 ug/kg. Administered over 10 minutes, beginning 10 minutes after the start of the ethanol/placebo clamp.; Drug: Placebo; Control: no alcohol, administered for a total of 90 minutes.; Drug: Placebo; Control: no iomazenil, administered for a total of 10 minutes
Placebo Comparator: Placebo Ethanol and Placebo Iomazenil; Participants will receive in a randomized, double-blind, cross-over design, ethanol or placebo and iomazenil or placebo. Potential Randomizations: a) active ethanol and placebo iomazenil, b) active ethanol and active iomazenil, c) placebo ethanol and active iomazenil, and d) placebo ethanol and placebo iomazenil	Drug: Placebo; Control: no alcohol, administered for a total of 90 minutes.; Drug: Placebo; Control: no iomazenil, administered for a total of 10 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biphasic Ethanol Effects Scale (BAES)	A 14-item scale with 7 items designated to assess stimulant effects associated with the ascending limb of ethanol intoxication and 7 items developed to measure sedative effects associated with the descending limb of ethanol intoxication. The BAES full scale would be 0 to 140. However, the scale itself is analyzed by breaking up the full 14 item scale into 2 parts - sedation and stimulation. Therefore, the total score for sedation ranges from 0 to 70, with higher scores indicating more sedation, and the total score for stimulation also ranges from 0 to 70, with higher scores indicating more stimulation. Timepoints: Administered 160 mins (M160) and 10 mins (M10) prior to the target ethanol/placebo dose being reached, when the target ethanol dose (BrAC of 0.1%)/placebo has been reached (0), and 15 (P15), 70 (P70), 90 (P90), and 150 (P150) minutes after the target ethanol/placebo dose has been reached.	Administered 160 mins and 10 mins prior to the target ethanol/placebo dose being reached, when the target ethanol dose (BrAC of 0.1%)/placebo has been reached, and 15, 70, 90, 150, and 240 minutes after the target ethanol/placebo dose has been reached.

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Deepak C D'Souza, MD MBBS, VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2012
• Primary Completion (Actual): November 2, 2018
• Study Completion (Actual): November 2, 2018

Study Registration Dates

• First Submitted: April 30, 2012
• First Submitted That Met QC Criteria: April 30, 2012
• First Posted (Estimated): May 2, 2012

Study Record Updates

• Last Update Posted (Actual): October 9, 2024
• Last Update Submitted That Met QC Criteria: September 18, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: CLIN-026-11F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No