Impact of Omega 3 in Alcohol Use Disorder

Alcohol Use Disorder, Severe Clinical Trial

— W3-AUD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05899660
• Other study ID #: 2022/22DEC/502
• Status: Recruiting
• Phase: N/A
• Start date: June 19, 2023
• Est. completion date: December 31, 2027

Study information

• Verified date: June 2023
• Source: Université Catholique de Louvain
• Contact: Sophie Leclercq, PhD
• Phone: +3224361023
• Email: sophie.leclercq[@]uclouvain.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2027
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder, Severe
• Alcoholism

Intervention

Dietary Supplement:
• Active Comparator: Omega-3
It is a dietary supplement made of fish oil rich in n-3 PUFA.
• Placebo Comparator: olive oil
Refined olive oil is the usual placebo used in studies with n-3 PUFA.

Locations

Country	Name	City	State
Belgium	Cliniques universitaires Saint Luc	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

References & Publications (2)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in depression	Beck Depression Inventory (BDI) (score 0-63) Higher score indicates higher depression level.	On day 2, day 19 and day 90
Primary	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
Primary	Change in fatigue	Multidimensional Fatigue Inventory (MFI) (score 20-140) Higher score indicates higher fatigue level.	On day 2, day 19 and day 90
Primary	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
Primary	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
Primary	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
Primary	Change in trauma	Post-traumatic diagnostic scale (PDS-F): calculation of score is complex and described in the related publication	On day 19
Primary	Childhood trauma	Childhood Trauma Questionnaire (CTQ) (28-144) Higher score indicates higher childhood trauma level.	On day 19
Primary	Self-stigma	Self-Stigma in Alcohol Dependence (SSAD) (16-80) Higher score indicates higher self-stigma level.	On day 19
Primary	Change in work memory	Letter Memory Task	On day 2, day 19 and day 90
Primary	Change in inhibition	Stop Signal Task	On day 2, day 19 and day 90
Primary	Change in decision making	Fisher Task	On day 19 and day 90
Primary	Change in facial emotions recognition	Facial Emotions Recognition Task (TREF)	On day 19 and day 90
Primary	Change in visual perspective taking	Visual Perspective Taking Task	On day 19 and day 90
Primary	Sociability	Sociogram	On day 19
Primary	Emotional intelligence	Trait Emotional Intelligence Questionnaire (TEI Que-75) : calculation of score is complex and described in the related publication	Day 19
Primary	Change in social activity	Social Activities Questionnaire (28-196)	On day 2, day 19 and day 90
Secondary	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
Secondary	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
Secondary	Change in gut microbiota composition	Analysis of gut microbiota (16S rDNA) by high-throughput sequencing (Illumina)	On day 2, day 19 and day 90
Secondary	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
Secondary	Change in omega-3 levels	Omega-3 levels in plasma and red blood cells	On day 2, day 19 and day 90
Secondary	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
Secondary	Change in brain functioning	Magnetic Resonance Imaging	On day 2, day 19 and day 90