Impact of Omega 3 in Alcohol Use Disorder (W3-AUD)

Impact of Omega-3 Polyunsaturated Fatty Acids on Emotional, Cognitive and Biological Alterations in Alcohol Use Disorder

The goal of this clinical trial is to investigate the biological pathways underlying the beneficial effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on mental health in patients with alcohol use disorder. The main questions this study aims to answer are:

• Can n-3 PUFA improve mood disorders (depression, anxiety), craving for alcohol, cognitive impairments and sociability disorders ?
• Are the beneficial effects of n-3 PUFAs due to a modification of the gut microbiota and/or the inflammatory status?

Participants will :

• take a supplementation of omega-3 or placebo during 3 months
• do a brain MRI
• be interviewed for a dietary anamnesis
• provide blood, stool and saliva samples
• perform psychological tests and neuropsychological tasks

Researchers will compare active comparator (omega-3) with placebo comparator (olive oil) to see if omega-3 can have a beneficial effect on AUD patients.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder, Severe
• Intervention / Treatment: Dietary supplement: Placebo Comparator: olive oil; Dietary supplement: Active Comparator: Omega-3

Detailed Description

Alcohol use disorder (AUD) is the most widespread addiction in Belgium and Europe and constitutes a major public health problem with important physical, psychological and economic consequences for the consumer and his family, friends, co-workers.

For several years, the intestinal microbiota has been increasingly studied because it seems to play an indispensable role in the proper functioning of the body. Indeed, it is involved in the regulation of the immune system, metabolic reactions and the nervous system and therefore influences behaviour. The composition of the microbiota is specific to everyone and is influenced by many factors, such as diet, medication and lifestyle.

In the case of AUD, numerous studies have shown that alcohol and its metabolites alter the intestinal microbiota, leading to an increase in inflammation and changes in behaviour.

Nutritional intervention is an encouraging and innovative approach to alcohol addiction therapy. The main aim of this research is to see how a nutritional intervention could improve mood, cognition and social behaviour in AUD patients. The interest will therefore focus on Omega-3. These polyunsaturated fatty acids are found in the diet, mainly in fish oils, and are constituents of the body's cell membranes and perform many physiological functions. They also play an important role in the regulation of inflammation. Studies have shown that Omega-3 supplementation can reduce symptoms of depression and have beneficial effects in autism spectrum disorders, schizophrenia, bipolar disorders and neurodegenerative diseases. They have therefore been widely studied, but their role in social interactions, which is an important factor in many mental illnesses including AUD, has not yet been studied.

The investigators will conduct a randomised, placebo-controlled, double-blind study, testing the impact of Omega-3 supplementation on AUD patients undergoing a detoxification program at the Saint-Luc University Hospital, Brussels, Belgium. 100 patients will be enrolled and the Omega 3/placebo supplementation will last for 3 months. The patients will be tested 3 times: T1 (2nd day of withdrawal), T2 (18th-19th day of withdrawal) and T3 (after 3 months of supplementation). The investigators hope to see a beneficial effect of omega-3 on social, emotional and cognitive deficits as well as brain functioning (fMRI). They will investigate the mechanisms involved, namely, changes in the composition of the gut microbiota, reduction of systemic inflammation, and production of bacterial metabolites with immune or neuroactive properties.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sophie Leclercq, PhD; Phone Number: +3224361023; Email: sophie.leclercq@uclouvain.be
• Study Contact Backup: Name: Marie Mornard; Email: marie.mornard@uclouvain.be

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires Saint Luc
    • Contact: Marie Mornard; Email: marie.mornard@uclouvain.be
    • Contact: Sophie Leclercq; Email: sophie.leclercq@uclouvain.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of alcohol use disorder (≥ 4 DSM-5 criteria)
• Patient at the hospital for a 3 week alcohol withdrawal program
• Gender : male and female
• Age : between 18 and 70 years old
• Language : french
• Alcohol consumption less than 48 jours before admission

Exclusion Criteria:

• Presence of another addiction, except for smoking and cannabis use
• Presence of a psychiatric comorbidity (axis 1 DSM-5)
• Current or recent use (< 2 months) of antibiotics, probiotics, fibre supplements
• Current or recent (< 2 months) use of omega-3 supplements
• Current or recent (< 2 months) use of oral anti-coagulants drugs
• Current or recent (< 2 months) double anti-platelet therapy
• Coagulation disorders
• Current or recent (< 1 month) use of non-steroidal anti-inflammatory drugs and glucocorticoids
• Morbid obesity : body mass index > 35 kg.m-2
• Bariatric surgery
• Type I diabetes and type II diabetes not stabilised (i.e. glycated haemoglobin > 7.2 and unstable drug treatments)
• Chronic inflammatory diseases
• Cancer (less than 5 years before admission)
• Presence of cirrhosis (Fibroscan® = F4 and echodoppler performed as part of clinical routine on patient admission)
• Known allergy to fish and seafood
• Any other comorbidity that would be a contraindication to the study in the judgement of the principal investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Olive oil; Dosage form : capsule Dosage : 1000 mg oleic acid (olive oil) + 3.6 mg D-α-tocopherol (vitamin E) Frequency : 4 capsules per day Duration : 3 months	Dietary supplement: Placebo Comparator: olive oil; Refined olive oil is the usual placebo used in studies with n-3 PUFA.
Active Comparator: Omega-3; Dosage form : capsule Dosage : 330 mg EPA, 220 mg DHA, 100 mg other n-3 PUFA + 3.6 mg D-α-tocopherol (vitamin E) Frequency : 4 capsules per day Duration : 3 months	Dietary supplement: Active Comparator: Omega-3; It is a dietary supplement made of fish oil rich in n-3 PUFA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in depression	Beck Depression Inventory (BDI) (score 0-63) Higher score indicates higher depression level.	On day 2, day 19 and day 90
Change in anxiety	State-Trait Anxiety Inventory (STAI) (score 20-80) Higher score indicates higher anxiety level.	On day 2, day 19 and day 90
Change in fatigue	Multidimensional Fatigue Inventory (MFI) (score 20-140) Higher score indicates higher fatigue level.	On day 2, day 19 and day 90
Change in alcohol craving	Obsessive Compulsive Drinking Scale (OCDS) (score 0-40) Higher score indicates higher craving level.	On day 2, day 19 and day 90
Change in impulsivity	Urgency Premeditation Perseverance Sensation seeking impulsive behavior scale (UPPS) : score of different subscales are calculated : "ugency" (0-48), "lack of premeditation" (0-44), "lack of perseverance" (0-40), "sensation seeking) (0-48). Higher score in the different subscales indicates higher impulsivity level.	On day 19 and day 90
Change in social anxiety	Liebowitz Scale of Social Anxiety (EASL) (score 0-144) Higher score indicates higher social anxiety level.	On day 19 and day 90
Childhood trauma	Childhood Trauma Questionnaire (CTQ) (28-144) Higher score indicates higher childhood trauma level.	On day 19
Self-stigma	Self-Stigma in Alcohol Dependence (SSAD) (16-80) Higher score indicates higher self-stigma level.	On day 19
Change in work memory	Letter Memory Task	On day 2, day 19 and day 90
Change in inhibition	Stop Signal Task	On day 2, day 19 and day 90
Change in decision making	Fisher Task	On day 19 and day 90
Change in facial emotions recognition	Facial Emotions Recognition Task (TREF)	On day 19 and day 90
Change in visual perspective taking	Visual Perspective Taking Task	On day 19 and day 90
Sociability	Sociogram	On day 19
Change in social activity	Social Activities Questionnaire (28-196)	On day 2, day 19 and day 90
Change in trauma	Post-traumatic diagnostic scale (PDS-F): calculation of score is complex and described in the related publication	On day 19
Emotional intelligence	Trait Emotional Intelligence Questionnaire (TEI Que-75) : calculation of score is complex and described in the related publication	Day 19

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in inflammation	Circulating pro- and anti-inflammatory cytokines (TNFa, IL-6, IL-1b, IL-8, IL-10) levels in blood sample Isolation of PBMC to study intracellular inflammatory pathways by RT-qPCR	On day 2, day 19 and day 90
Change in gut microbiota composition	Analysis of gut microbiota (16S rDNA) by high-throughput sequencing (Illumina)	On day 2, day 19 and day 90
Intestinal permeability	a duodenal biopsy will be collected and the expression of the tight junctions regulation the intestinal permeability will be analyzed by sectional immunofluorescence and quantitative polymerase chain reaction	On day 19
Change in omega-3 levels	Omega-3 levels in plasma and red blood cells	On day 2, day 19 and day 90
Change in diet profile	The dietary anamnesis will consist of a 24-hour recall over 3 days (2 weekdays and 1 weekend day)	On day 2, day 19 and day 90
Change in brain functioning	Magnetic Resonance Imaging	On day 2, day 19 and day 90
Change in markers of microbial translocation	measurement of sCD14, PGRP in blood sample using ELISA kits (pg/mL)	On day 2, day 19 and day 90

Collaborators and Investigators

• Sponsor: Université Catholique de Louvain
• Investigators: Principal Investigator: Philippe de Timary, MD, PhD, St Luc academic Hospital and Université Catholique de Louvain; Principal Investigator: Peter Starkel, MD, PhD, St Luc academic Hospital and Université Catholique de Louvain

Publications and helpful links

General Publications

• Hearn, M, Ceschi, G., Brillon, P, Fürst, G., & Van der Linden, M. (2012). A French adaptation of the Post-traumatic Diagnostic scale. Canadian Journal of Behavioural Science, 44, 16-28
• Petrides KV (2009) Psychometric properties of the trait emotional intelligence questionnaire. In: Stough C, Saklofske DH, Parker JD (eds) Advances in the assessment of emotional intelligence. Springer, New York. 10.1007/978-0-387-88370-0_5

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: June 1, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Depression; Inflammation; Anxiety; Cognition; Omega 3; gut microbiota; metabolomics; Brain imaging; Alcohol craving; Sociability
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism
• Other Study ID Numbers: 2022/22DEC/502

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: No
• Studies a U.S. FDA-regulated device product: No