Clinical trial NCT05899660: Impact of Omega 3 in Alcohol Use Disorder
Official title: Impact of Omega-3 Polyunsaturated Fatty Acids on Emotional, Cognitive and Biological Alterations in Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alcohol Use Disorder, Severe
Keywords: gut microbiota
Omega 3
metabolomics
Depression
Anxiety
Alcohol craving
Sociability
Cognition
Inflammation
Brain imaging
Lead sponsor: Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2023-06-12
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in depression
timeFrame: On day 2, day 19 and day 90
measure: Change in anxiety
timeFrame: On day 2, day 19 and day 90
measure: Change in fatigue
timeFrame: On day 2, day 19 and day 90
measure: Change in alcohol craving
timeFrame: On day 2, day 19 and day 90
measure: Change in impulsivity
timeFrame: On day 19 and day 90
measure: Change in social anxiety
timeFrame: On day 19 and day 90
measure: Change in trauma
timeFrame: On day 19
measure: Childhood trauma
timeFrame: On day 19
measure: Self-stigma
timeFrame: On day 19
measure: Change in work memory
timeFrame: On day 2, day 19 and day 90
measure: Change in inhibition
timeFrame: On day 2, day 19 and day 90
measure: Change in decision making
timeFrame: On day 19 and day 90
measure: Change in facial emotions recognition
timeFrame: On day 19 and day 90
measure: Change in visual perspective taking
timeFrame: On day 19 and day 90
measure: Sociability
timeFrame: On day 19
measure: Emotional intelligence
timeFrame: Day 19
measure: Change in social activity
timeFrame: On day 2, day 19 and day 90
Secondary outcomes:
measure: Change in markers of microbial translocation
timeFrame: On day 2, day 19 and day 90
measure: Change in inflammation
timeFrame: On day 2, day 19 and day 90
measure: Change in gut microbiota composition
timeFrame: On day 2, day 19 and day 90
measure: Intestinal permeability
timeFrame: On day 19
measure: Change in omega-3 levels
timeFrame: On day 2, day 19 and day 90
measure: Change in diet profile
timeFrame: On day 2, day 19 and day 90
measure: Change in brain functioning
timeFrame: On day 2, day 19 and day 90
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint Luc
Study officials:
affiliation: St Luc academic Hospital and Université Catholique de Louvain
name: Philippe de Timary, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St Luc academic Hospital and Université Catholique de Louvain
name: Peter Starkel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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
citation: 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