Fish Oil vs. Placebo on Subjective Effects of Alcohol

Effect of Fish Oil vs. Placebo on Subjective Effects of Alcohol in Healthy Humans

This project represents a first step in examining the potential use of fish oil for the treatment of alcohol use disorder (AUD). The investigators will be testing for attenuation of alcohol-induced sedative and stimulant effects, as well as cognitive effects and cerebellar effects in healthy social drinkers.

Study Overview

• Status: Completed
• Conditions: Alcohol Dependence
• Intervention / Treatment: Drug: Fish Oil with ethanol and placebo ethanol infusions; Drug: Placebo with ethanol and placebo ethanol infusions

Detailed Description

There have been no studies to date that have examined the relationship between fish oil and alcohol response in humans. The current study was designed to examine the relationship between fish oil and subjective alcohol effects in healthy social drinkers.

This project represents a first step in examining the potential use of fish oil for the treatment of alcohol use disorder (AUD). The investigators will evaluate responses to alcohol through administration of a steady state blood alcohol level (BAL) with an IV infusion using a method that employs an infusion that is titrated to a breathalyzer reading and clamped at a steady state. This approach allows direct comparisons of the acute effects of a specific dose of ethanol between groups, without the confounding factors of variable alcohol absorption and peak BAL's. This approach will allow the examiners to carefully examine if fish oil changes the acute effects of alcohol on a number of outcome domains including subjective drug effects, cognitive performance, and cerebellar effects.

As this study is a pilot study, it is not clear whether fish oil will attenuate alcohol induced subjective stimulation or sedation. Since this is the first study to evaluate fish oil's effects on alcohol-effects in the laboratory, the investigators will be testing for attenuation of alcohol-induced sedative and stimulant effects, as well as cognitive effects and cerebellar effects.

In this study, fish oil will be administered at 3 grams/day for 30-40 days (3 capsules twice a day). The investigators will use 3 grams/day for two reasons: 1) it is within the range of doses safely used in humans (1g to 6g) as a treatment for various psychiatric conditions (depression, anxiety, borderline personality disorder), and 2) is a dose that has shown efficacy in various clinical trials for psychiatric conditions.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healtcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and females, between the ages of 21 and 55;
2. No current drug use disorder of any drugs of abuse (except tobacco or marijuana);
3. No current medical problems and normal ECG;
4. For women, not pregnant as determined by pregnancy screening nor breast feeding, and using acceptable birth control methods.

Exclusion Criteria:

1. Current major psychiatric illnesses including mood, psychotic, or anxiety disorders;
2. History of major medical illnesses; including liver diseases, heart disease, chronic pain or other medical conditions that the physician investigator deems contraindicated for the subject to be in the study;
3. Liver function tests (ALT or AST) greater than 3 times normal;
4. Allergy to seafood.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fish Oil with ethanol and placebo ethanol infusions; Between days 30-40 subjects will participate in 2 test days at least 2 days apart and during the test day will receive an IV infusion of ethanol (placebo vs. targeted Breath Alcohol Concentration ((BrAC) of 100mg%) in a clamped fashion. Test days will be in a randomized order.	Drug: Fish Oil with ethanol and placebo ethanol infusions; Fish Oil with ethanol and placebo ethanol infusions
Placebo Comparator: Placebo with ethanol and placebo ethanol infusions; Between days 30-40 subjects will participate in 2 test days at least 2 days apart and during the test day will receive an IV infusion of ethanol (placebo vs. targeted Breath Alcohol Concentration ((BrAC) of 100mg%) in a clamped fashion. Test days will be in a randomized order.	Drug: Placebo with ethanol and placebo ethanol infusions; Placebo with ethanol and placebo ethanol infusions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of stimulant and sedative effects of alcohol with the Biphasic Alcohol Effects Scale (BAES).	The BAES is a 14-item self-report scale. Seven items measure stimulant effects of alcohol during the test sessions and seven items measure sedative effects. Stimulant and sedative effect scores range from 0 (not at all) to 70 (extremely).	Baseline
Assessment of stimulant and sedative effects of alcohol with the Biphasic Alcohol Effects Scale (BAES).		Week 4 (test session 1)
Assessment of stimulant and sedative effects of alcohol with the Biphasic Alcohol Effects Scale (BAES).		Week 6 (test session 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive performance measured with the Rapid Information Processing Task (RVIP)	(RVIP) is a widely used task to assess sustained attention, with a working memory component. In this task, a series of single digits is presented on a computer screen at a rate of 100 digits per minute for 4 min. Targets are defined as three consecutive odd digits (e.g., 7-9-3) or three consecutive even digits (e.g., 2-8-6). The percentage of targets correctly detected will be the main outcome measure.	Baseline
Cognitive performance measured with the Rapid Information Processing Task (RVIP)	(RVIP) is a widely used task to assess sustained attention, with a working memory component. In this task, a series of single digits is presented on a computer screen at a rate of 100 digits per minute for 4 min. Targets are defined as three consecutive odd digits (e.g., 7-9-3) or three consecutive even digits (e.g., 2-8-6). The percentage of targets correctly detected will be the main outcome measure.	Week 4 (test session 1)
Cognitive performance measured with the Rapid Information Processing Task (RVIP)	(RVIP) is a widely used task to assess sustained attention, with a working memory component. In this task, a series of single digits is presented on a computer screen at a rate of 100 digits per minute for 4 min. Targets are defined as three consecutive odd digits (e.g., 7-9-3) or three consecutive even digits (e.g., 2-8-6). The percentage of targets correctly detected will be the main outcome measure.	Week 6 (test session 2)
Cognitive performance measured by a "Go No-Go task" will assess the ability to withhold responses to an infrequently occurring target.	A series of blue and green rectangular shapes are presented every 1150 ms and participants are instructed to press a spacebar every time the green rectangular shape appeared, and to give equal importance to speed and accuracy. The primary outcome is the number of errors on the No-Go trials.	Baseline
Cognitive performance measured by a "Go No-Go task" will assess the ability to withhold responses to an infrequently occurring target.	A series of blue and green rectangular shapes are presented every 1150 ms and participants are instructed to press a spacebar every time the green rectangular shape appeared, and to give equal importance to speed and accuracy. The primary outcome is the number of errors on the No-Go trials.	Week 4 (test session 1)
Cognitive performance measured by a "Go No-Go task" will assess the ability to withhold responses to an infrequently occurring target.	A series of blue and green rectangular shapes are presented every 1150 ms and participants are instructed to press a spacebar every time the green rectangular shape appeared, and to give equal importance to speed and accuracy. The primary outcome is the number of errors on the No-Go trials.	Week 6 (test session 2)
Cognitive performance measured by the Hopkins Verbal Learning Test-Revised (HVLT-R).	The HVLT-R is a word list learning test of verbal memory. The outcome is the percent correct on immediate and delayed recall of words on a list.	Baseline
Cognitive performance measured by the Hopkins Verbal Learning Test-Revised (HVLT-R).	The HVLT-R is a word list learning test of verbal memory. The outcome is the percent correct on immediate and delayed recall of words on a list.	Week 4 (test session 1)
Cognitive performance measured by the Hopkins Verbal Learning Test-Revised (HVLT-R).	The HVLT-R is a word list learning test of verbal memory. The outcome is the percent correct on immediate and delayed recall of words on a list.	Week 6 (test session 2)
Motor Impairment: The Grooved Pegboard Test (Lafayette Instrument Company) is a manipulative dexterity test,	This is an eye-to hand timed coordination test. A quicker time indicates greater coordination.	Baseline
Motor Impairment: The Grooved Pegboard Test (Lafayette Instrument Company) is a manipulative dexterity test,	This is an eye-to hand timed coordination test. A quicker time indicates greater coordination.	Week 4 (test session 1)
Motor Impairment: The Grooved Pegboard Test (Lafayette Instrument Company) is a manipulative dexterity test,	This is an eye-to hand timed coordination test. A quicker time indicates greater coordination.	Week 6 (test session 2)

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: VA Connecticut Healthcare System
• Investigators: Principal Investigator: Ismene Petrakis, M.D., Yale University/VA Connecticut Healthcare System

Publications and helpful links

General Publications

• Subramanian MG, Heil SH, Kruger ML, Collins KL, Buck PO, Zawacki T, Abbey A, Sokol RJ, Diamond MP. A three-stage alcohol clamp procedure in human subjects. Alcohol Clin Exp Res. 2002 Oct;26(10):1479-83. doi: 10.1097/01.ALC.0000034038.41972.36.
• Zimmermann US, O'Connor S, Ramchandani VA. Modeling alcohol self-administration in the human laboratory. Curr Top Behav Neurosci. 2013;13:315-53. doi: 10.1007/7854_2011_149.
• Ramchandani VA, O'Connor S, Blekher T, Kareken D, Morzorati S, Nurnberger J Jr, Li TK. A preliminary study of acute responses to clamped alcohol concentration and family history of alcoholism. Alcohol Clin Exp Res. 1999 Aug;23(8):1320-30.

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2017
• Primary Completion (Actual): May 30, 2021
• Study Completion (Actual): September 8, 2021

Study Registration Dates

• First Submitted: December 15, 2016
• First Submitted That Met QC Criteria: January 3, 2017
• First Posted (Estimate): January 5, 2017

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Alcohol Dependence; Fish Oil
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: 1609018478

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