Study on Thiamine Supplementation to REduce braiN Injury Associated With Chronic Alcohol Use in Outpatients With Alcohol Use Disorder

NCT07844720 | Not Yet Recruiting Phase 2

• 3 other identifiers: C25-962025-524148-36-002025
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic alcohol use and alcohol use disorder (AUD) affect 10% of the population in France. They are associated with brain damage and cognitive impairment. These complications have a significant impact on patients' agency, autonomy, and ability to participate in their own care. The investigators need to improve our knowledge of medical treatments that can reduce these risks and harms, beyond providing support to quit drinking or reduce consumption. Nutritional and vitamin deficiencies, particularly thiamine deficiency, are involved in the onset of these complications. Thiamine deficiency causes Wernicke encephalopathy, which can lead to Korsakoff syndrome, a very severe episodic memory disorder. Blood tests to measure thiamine levels are not available in routine medical practice. And it is not currently covered by health insurance in France. However, the systematic prescription of thiamine is recommended during alcohol withdrawal by medical associations and health institutions in France and internationally. However, there are no clinical trial data in the international scientific literature demonstrating the medical benefits and required dosage of systematic supplementation outside the withdrawal period when alcohol use continues or when the patient does not seek alcohol abstinence. People who use multiple psychoactive substances, are in precarious situations, and are receiving treatment for substance use disorders at addiction treatment centers are particularly vulnerable to malnutrition and vitamin deficiencies. In this context, the place of systematic thiamine prescription arises with the aim of reducing risks and brain damage in patients who do not wish to or cannot stop their chronic alcohol use. One of the limitations of previous studies has been the lack of a suitable, reproducible, minimally invasive, inexpensive, and sensitive biomarker of therapeutic response. In this study, the investigators will use plasma neurofilament light chain (NFL) levels, an innovative biomarker. In two recent studies, the study team demonstrated the relevance of this biomarker and its effectiveness in measuring brain suffering in patients with AUD and its kinetics during during inpatient alcohol withdrawal. The hypothesis the invastigators are working on is that, in a population at high risk of vitamin and nutritional deficiency and who are chronic alcohol users, systematic supplementation with thiamine (vitamin B1) would reduce the brain suffering associated with this deficiency and chronic alcohol use. To answer this question, the investigators conduct a randomized, open-label pilot study. The primary objective is to test the efficacy of thiamine supplementation in reducing brain suffering as measured by plasma NFL level in chronic alcohol users with alcohol use disorder. Secondary objectives are to perform analyses of potential moderating factors of the treatment effect (per-protocol analysis based on good adherence, presence of morning alcohol withdrawal symptoms, reported morning alcohol use) and to use plasma glial fibrillary acidic protein (GFAP) and total plasma total tau protein as alternative biomarkers. the investigators include adult patients under the age of 65 with alcohol use disorder who are currently chronic active alcohol users reporting daily intake of at least 40g of alcohol, who are being treated in outpatient addiction treatment center, and who may have another substance use disorder as a comorbidity. This pilot study compares a group receiving 500 mg of thiamine supplementation in the morning and evening (1000 mg/day) over a period of 14 days with a control group receiving no supplementation. In order to measure the brain injury induced and its reduction, the investigators will measure plasma NFL level. Two measurements are performed, before supplementation begins (baseline, on day 0) and after two weeks of supplementation (follow-up visit, on days 14, 15, or 16). The primary judgment criterion is the change in plasma NFL level between baseline and follow-up, comparatively between the treatment group and the control group (time x treatment interaction). A repeated measures analysis of variance (ANOVA) test, adjusted for age and sex, is used.

Conditions

Alcohol Use Disorder

Keywords

alcohol use disorder; vitamin; thiamine; alcohol-related brain damage; neurofilament light chain

Outcome Measures

Primary Outcomes (1)

• Change in plasma NFL between the two arms, in ITT analysis

  Change in plasma neurofilament light chain (NFL) level between baseline (measured on day 0) and after 14 days of thiamine treatment or no intervention (measured on days 14, 15, or 16), comparatively between the two arms (time x treatment interaction in a repeated measures analysis of variance (ANOVA)), in an intention-to-treat analysis (ITT), adjusted for sex (phenotype, assigned at birth) and age.

  baseline (day 0) and follow-up (on days 14, 15, or 16)

Secondary Outcomes (5)

• Change in plasma NFL between the two arms, in PP analysis

  baseline (day 0) and follow-up (on days 14, 15, or 16)

• Interaction with the presence of morning alcohol withdrawal symptoms on plasma NFL change

  baseline (day 0) and follow-up (on days 14, 15, or 16)

• Interaction with reported alcohol use in the morning on plasma NFL change

  baseline (day 0) and follow-up (on days 14, 15, or 16)

• Change in plasma GFAP level between the two arms

  baseline (day 0) and follow-up (on days 14, 15, or 16)

• Change in plasma total tau level between the two arms

  baseline (day 0) and follow-up (on days 14, 15, or 16)

Other Outcomes (28)

• Interaction with self-reported daily alcohol intake on plasma NFL change

  baseline (day 0) and follow-up (on days 14, 15, or 16)

• Interaction with self-reported use of cocaine or psychostimulants during the treatment period on plasma NFL change

  baseline (day 0) and follow-up (on days 14, 15, or 16)

• Interaction with opioid agonist therapy on plasma NFL change

  baseline (day 0) and follow-up (on days 14, 15, or 16)

Study Arms (2)

Thiamine

EXPERIMENTAL

Thiamine 500mg twice daily for 14 days

Drug: Thiamine

Control

NO INTERVENTION

Interventions

Thiamine DRUG

Thiamine 500mg twice daily for 14 days

Also known as: Bevitine

Thiamine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with moderate to severe alcohol use disorder
• Reported daily consumption of at least 40g of alcohol
• Patients aged 18 to 65
• Contraceptive method (with a Pearl index ≤10) for women of childbearing age who are sexually active
• Covered by a health insurance plan or medical aid program
• Thiamine intake during the previous month
• Planned hospitalization during the study period
• Surgery with general anesthesia planned during the study period
• History of Wernicke encephalopathy, delirium tremens or severe cognitive impairment
• Epileptic seizure, stroke or severe head injury in the last three months
• Active infection with HIV, hepatitis C virus, or syphilis
• Severe hepatic impairment (prothrombin ratio below 50%)
• Severe renal impairment (glomerular filtration rate \<30 mL/min/1.73 m²)
• Persons subject to legal protection measures or under guardianship
• Pregnant women and breastfeeding women

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Hospital Lariboisière Fernand-Widal

Paris, Île-de-France Region, 75010, France

Location

MeSH Terms

Conditions

Alcoholism; Charcot-Marie-Tooth disease, Type 1F

Interventions

Thiamine

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Virgile Clergue-Duval, MD PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Florence Vorspan, MD PhD

  Inserm UMR-S 1144 Therapeutic optimization in neuropharmacology

  STUDY DIRECTOR

Central Study Contacts

Virgile Clergue-Duval, MD PhD

CONTACT

0033140054214; virgile.clergue-duval@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2026
• First Posted: September 28, 2026
• Study Start (Estimated): October 23, 2026
• Primary Completion (Estimated): October 22, 2027
• Study Completion (Estimated): October 22, 2027
• Last Updated: September 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)