Dietary Fiber Intake in Alcohol-dependent Patients

The alcohol problem affects 7.5% of the population in Europe and represents a major public health problem. Alcoholism is also a major cause of undernutrition. Diet is a major factor influencing the composition of the intestinal microbiota and previous studies, carried out at Saint-Luc clinics and catholic university of Louvain, show that alcoholic patients suffer from dysbiosis, that is a significant alteration of the gut microbiota. The investigator's preliminary studies, carried out at the Integrated Unit of Hepatology of Saint-Luc Clinics, have shown that alcohol represents more than 40% of total caloric intake in alcohol-dependent patients. In addition, alcoholic patients have an insufficient intake of dietary fiber, that is to say a contribution lower than the Belgian nutritional recommendations. Indeed, the Conseil Supérieur de la Santé recommends a total amount of dietary fiber equal to or greater than 25 grams per day to ensure correct intestinal function. Fructan-type dietary fiber (inulin and fructo-oligosaccharides) is found naturally in many fruits and vegetables (Jerusalem artichokes, asparagus, artichokes, onions, garlic, chicory roots, bananas). They are neither absorbed nor digested by human enzymes but fermented selectively by intestinal bacteria.

A good digestive tolerance to dietary fiber supplementation has been observed in healthy subjects as well as in obese patients, in previous studies conducted at catholic university of Louvain and Saint-Luc clinics. However, a nutritional rebalance via fiber supplementation and digestive fiber tolerance have never been tested in an alcohol-dependent population.

The primary objectives of this academic research project in nutrition, carried out in alcohol-dependent patients, are as follows:

1. restore a nutritional balance as recommended by the Conseil Supérieur de la Santé via a dietary fiber intake
2. to study digestive tolerance to fibers
3. to study the intestinal and psychological well-being related to a fiber intake

Depending on the results obtained during the achievement of the primary objectives, the biological samples (blood, stool) collected during the study will be used to analyze the composition of the intestinal microbiota and the plasma markers associated with intestinal function.

Study Overview

• Status: Unknown
• Conditions: Alcoholism
• Intervention / Treatment: Dietary supplement: placebo; Dietary supplement: inulin

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Stärkel, MD, PhD; Phone Number: 003227642853; Email: peter.starkel@uclouvain.be

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • Université Catholique de Louvain
    • Contact: Peter Stärkel, MD, PhD; Phone Number: 003227642853; Email: peter.starkel@uclouvain.be
    • Principal Investigator: Peter Stärkel, MD, PhD
    • Sub-Investigator: Nathalie Delzenne, PhD
    • Sub-Investigator: Sophie Leclercq, PhD
    • Sub-Investigator: Philippe de Timary, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• male or female
• aged between 18 and 65
• caucasian
• French speaking
• alcohol drunk less than 48h before day 1

Exclusion Criteria:

• another addiction, except smoking
• psychiatric comorbidity on axe 1 of Diagnostic and Statistical Manual-IV
• antibiotic, probiotic or fibers recent (<2 months) treatment (or other molecule modifying intestinal transit)
• Non-steroidial anti-inflammatory drug or glucocorticoids recently taken (<1 month)
• obesity: Body Mass Index<30
• bariatric surgery
• Type 1 or 2 diabetes
• chronic inflammatory diseases (Crohn disease, coeliac disease, rheumatoid arthritis)
• cirrhosis or Advanced hepatic fibrosis (Fibroscan > or = F3)
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; maltodextrin received at 4g/day on day 3 and 4; maltodextrin received at 8g/day from day 5 to 14; maltodextrin received at 16g/day from day 15 to 20	Dietary supplement: placebo; maltodextrine given at different dosis from day 3 to day 20
Experimental: inulin; inulin received at 4g/day on day 3 and 4; inulin received at 8g/day from day 5 to 14; inulin received at 16g/day from day 15 to 20	Dietary supplement: inulin; inulin given at different dosis from day 3 to day 20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in diet profile	This tool is based on the one adapted to alcoholic patients at Saint Luc Hospital. It consists of two parts to allow cross-checking of data (redundancy) and to measure separate information: General: it is implemented a Food Frequency Questionnaire (FFQ) in order to investigate the general diet profile. Daily: it resumes the sequencing of a full day which allows to verify the information previously obtained as well as to precisely identify the moments of consumption of alcoholic and non-alcoholic inputs. This 7-day recall will be carried out at two times: week T1 for reminder of the week before hospitalization then T2 for reminder of the week back home. In this last case, this anamnesis will be done by interview, but also on the basis of the diary filled by the patient in T2, in order to optimize the accuracy of the data.	on Day 2 and Day 19

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alimentary book	The patient will have to fill in this book every day	From day 1 to day 21
Quantitative evaluation of intakes	The meals will be weighted before and after eating	on Day 2 and Day 19
Alimentation history	This questionnaire makes it possible to further investigate the patient's diet before the episode of alcoholism in his adult and child life. The aim is to assess whether it is closer to a healthy diet (Mediterranean diet or dash diet) or a Western diet type. It is based on the recall technique and performed by a qualified dietician.	On day 21
Change in mood	Beck Depression Inventory (score 0-63). Higher score indicates higher depression level.	on Day 2 and Day 19
Change in anxiety	State-Trait Anxiety Inventory (score 20-80). Higher score indicates higher anxiety level.	on Day 2 and Day 19
Change in alcohol craving	Obsessive Compulsive Drinking Scale: a total score (= obsession + compulsion) (0-40) and 2 sub-scores (Obsession (0-20) and Compulsion (0-20)) are calculated. Higher score indicates higher craving level.	on Day 2 and Day 19
Change in impulsivity	Urgency Premeditation Perseverance Sensation seeking impulsive behavior scale: score of different subscales are calculated: "urgency"(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 2 and Day 19
Change in selective attention	William Lennox attention tests	on Day 2 and Day 19
Change in work memory	Brown-Peterson's tasks	on Day 2 and Day 19
Change in flexibility	Trail making test	on Day 2 and Day 19
Change in inhibition	Scoop's tasks	on Day 2 and Day 19
Change in decision making	Iowa gambling's task	on Day 2 and Day 19
Change in trauma	Post-traumatic diagnostic scale: calculation of score is complex and described in the related publication 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.	on Day 2 and Day 19
Change in intestine integrity	It will be determined by blood sample (LPS level)	on Day 2 and Day 19
Change in albumin, pre-albumin and zinc concentration	It will be determined by blood sample	on Day 2 and Day 19
Change in intestinal permeability	Patients will ingest 50microCurie of 51Chrome-Ethylenediamintetraacetic prepared in a Nutridrink®. This molecule is not normally absorbed by the intestine except when there is an increase in intestinal permeability (paracellular passage following rupture of tight junctions). The molecule is then filtered by the kidney and is found in the urine. A 24h urine collection will be carried out to measure the radioactivity emitted by 51Chrome-Ethylenediamintetraacetic	on Day 2 and Day 19
Change in fecal albumin concentration	A stool sample will be collected to analyze a marker of intestinal permeability: fecal albumin	on Day 2 and Day 19
Intestinal permeability	a duodenal biopsy will be collected and the expression of the tight junctions regulating the intestinal permeability will be analyzed by sectional immunofluorescence and quantitative Polymerase Chain reaction	On day 3

Collaborators and Investigators

• Sponsor: Université Catholique de Louvain

Publications and helpful links

General Publications

• Amadieu C, Maccioni L, Leclercq S, Neyrinck AM, Delzenne NM, de Timary P, Stärkel P. Liver alterations are not improved by inulin supplementation in alcohol use disorder patients during alcohol withdrawal: A pilot randomized, double-blind, placebo-controlled study. EBioMedicine. 2022 Jun;80:104033. doi: 10.1016/j.ebiom.2022.104033. Epub 2022 Apr 28.
• Amadieu C, Coste V, Neyrinck AM, Thijssen V, Leyrolle Q, Bindels LB, Piessevaux H, Stärkel P, de Timary P, Delzenne NM, Leclercq S. Restoring an adequate dietary fiber intake by inulin supplementation: a pilot study showing an impact on gut microbiota and sociability in alcohol use disorder patients. Gut Microbes. 2022 Jan-Dec;14(1):2007042. doi: 10.1080/19490976.2021.2007042.
• Amadieu C, Leclercq S, Coste V, Thijssen V, Neyrinck AM, Bindels LB, Cani PD, Piessevaux H, Starkel P, de Timary P, Delzenne NM. Dietary fiber deficiency as a component of malnutrition associated with psychological alterations in alcohol use disorder. Clin Nutr. 2021 May;40(5):2673-2682. doi: 10.1016/j.clnu.2021.03.029. Epub 2021 Mar 30.

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2017
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: December 13, 2018
• First Submitted That Met QC Criteria: January 10, 2019
• First Posted (Actual): January 15, 2019

Study Record Updates

• Last Update Posted (Actual): February 7, 2019
• Last Update Submitted That Met QC Criteria: February 5, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: dietary fibers; alcohol-dependent
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism
• Other Study ID Numbers: 190616V1; 2017/04JUL/354 (Other Identifier: Ethics Committee CEHF)

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