Randomised open-label pilot Study on Thiamine supplementation to REduce braiN injury associated with chronic Alcohol use in outpatients with alcohol use disorder : STRENA

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut National De La Sante Et De La Recherche Medicale

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Decision date (initial)

2026-06-29

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Institute for Public Health Research (IReSP)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective is to evaluate the efficacy of a 14-day course of thiamine supplementation in reducing brain damage, as measured by plasma levels of light neurofilaments (NFL), in patients who are chronic alcohol users and have an alcohol use disorder, using an intention-to-treat (ITT) analysis.

Secondary objectives 4

1. An initial set of three secondary objectives was defined in the protocol with the aim of investigating the variability of the primary endpoint, using plasma NFL levels as a marker of response. The primary question regarding the therapeutic efficacy of thiamine will be analyzed per protocol (PP), using the criterion of reported intake of at least 80% of thiamine tablets (45 out of 56) as an indicator of good adherence and effective treatment intake. Next, the question of therapeutic efficacy will be analyzed by introducing a mediating factor into the ANOVA. We have identified, first and foremost, two clinical factors of interest: the presence of morning alcohol withdrawal symptoms and self-reported morning alcohol consumption. These are dichotomous factors. They were chosen as markers of greater pharmacological dependence on alcohol and for their clinical relevance in assessing the severity of alcohol use disorder. We do not make any assumptions regarding the direction of the interaction, namely whether treatment would be more effective in the group with greater severity or vice versa. The aim is to provide elements to discuss the main result and to design the future clinical trial.
2. A second set of two secondary objectives was then established to evaluate the alternative plasma biomarkers measured in this study (plasma GFAP and Tau). These two secondary objectives will replicate the primary endpoint for therapeutic efficacy by using plasma GFAP and Tau as biomarkers of therapeutic response.
3. To further the study’s exploratory strategy, a series of additional secondary objectives were subsequently incorporated into the protocol, utilizing descriptive data on the study population and the presence of addictive and neurocognitive comorbidities. These objectives aim to further explore the variability in the therapeutic effect of thiamine by measuring plasma NFL levels. Three additional clinical interaction factors will thus be tested using repeated measures ANOVA: the patient’s self-reported daily alcohol consumption at T1 (continuous variable), reported use of cocaine or psychostimulants during the treatment period between T1 and T2 (dichotomous variable), and prescription use of an opioid agonist medication (OAM) (buprenorphine or methadone) (dichotomous variable). Plasma GFAP and Tau levels will then be examined as alternative biomarkers by performing the tests previously described for plasma NFLs. Particular attention will also be paid to exploring the relevance of the Montreal Cognitive Assessment (MoCA) screening test and the impulsivity subscale of the Difficulties in Emotion Regulation Scale (DERS) in this population and their associations with plasma biomarker levels. Alcohol craving will also be studied using the Obsessive Compulsive Drinking Scale (OCDS) questionnaire. Treatment adherence criteria will also be analyzed.
4. A proteomic analysis will be conducted to investigate the mechanisms underlying the therapeutic effect of vitamin B1 in reducing brain damage

Conditions and MedDRA coding

Alcoholism

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients being treated for moderate or severe alcohol use disorder
2. Reported daily alcohol consumption of at least 40 g
3. Patients aged 18 to 65
4. A urine pregnancy test performed prior to enrollment for women of childbearing age
5. Use of contraception for women of childbearing age who are sexually active
6. Enrollment in a social security program or the Aide Médicale d’État program, or eligibility for such a program.

Exclusion criteria 13

1. Use of thiamine within the past month
2. Planned hospitalization during the study period
3. Scheduled surgical procedure under general anesthesia during the study period
4. History of Wernicke’s encephalopathy, delirium tremens, or severe cognitive impairment
5. Epileptic seizure, stroke, or severe head trauma within the last three months
6. Active infection with HIV, hepatitis C virus (HCV), or syphilis
7. Glomerular filtration rate (GFR) <50%
8. Severe renal impairment (eGFR <30 mL/min/1.73 m²)
9. Individuals subject to legal guardianship, conservatorship, or trusteeship
10. Pregnant and breastfeeding women
11. Known or suspected allergy to any of the ingredients in the investigational drug Bevitine (thiamine)
12. Known or suspected wheat allergy (other than celiac disease)
13. Fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the change in plasma light neurofilaments (NFL) between the day treatment began (T1; Day 0) and after 14 days of treatment (T2) (days 14, 15, or 16), comparing the thiamine treatment group with the control group without supplementation (time × treatment interaction in a repeated-measures analysis of variance (ANOVA)), in an intention-to-treat (ITT) analysis, adjusted for sex (phenotype assigned at birth) and age.

Secondary endpoints 9

1. Repeated-measures ANOVA of plasma NFL levels (T1–T2): (1) effect of thiamine supplementation vs control (time × treatment interaction) in per-protocol analysis with ≥80% adherence, adjusted for age and sex; (2) in ITT, effect of supplementation, morning alcohol withdrawal symptoms, and their interaction; (3) in ITT, effect of supplementation, reported morning alcohol consumption, and their interaction, adjusted for age and sex.
2. Variation in plasma GFAP and total Tau levels between T1 and T2 will be compared between the thiamine supplementation group and the control group without supplementation using repeated-measures ANOVA (time × treatment interaction), in an intention-to-treat (ITT) analysis adjusted for age and sex.
3. Additional analyses of treatment effect variability using plasma NFL: repeated-measures ANOVA (T1–T2) assessing supplementation effect (time×treatment), daily alcohol intake at T1, psychostimulant use, or OAT use, and their interactions (ITT, adjusted for age and sex). Linear regression between changes in NFL and alcohol intake. Associations of NFL at T1 with clinical and social factors, followed by multivariate analysis (p≤0.10).
4. Plasma GFAP variation between T1 and T2 compared between thiamine and control groups using repeated-measures ANOVA (time×treatment), per-protocol (≥80% adherence), adjusted for age and sex. In ITT, analyses assess supplementation, withdrawal symptoms, morning alcohol use, alcohol quantity at T1, psychostimulant or OAT use and interactions. Linear regressions between GFAP and alcohol changes; associations at T1 with clinical/social factors, then multivariate analysis (p<0.10).
5. Plasma total Tau variation between T1 and T2 compared between thiamine and control groups using repeated-measures ANOVA (time×treatment), per-protocol (≥80% adherence), adjusted for age and sex. In ITT, analyses assess supplementation, withdrawal symptoms, morning alcohol use, alcohol quantity at T1, psychostimulant or OAT use and interactions. Linear regressions between Tau and alcohol changes, associations at T1 with clinical and social factors, followed by multivariate analysis (p≤0.10).
6. MoCA score analysis: linear regression adjusted for age and sex of the MoCA score at T1 with age and sex alone, morning alcohol withdrawal symptoms, active cocaine use in the previous month, OAT use, EPICES deprivation score, homelessness status, DERS impulsivity subscale, and OCDS score at T1. Multivariate analysis will follow including factors with p≤0.10 in univariate analysis.
7. Alcohol craving analysis: change in OCDS score between T1 and T2 compared between thiamine and control groups using repeated-measures ANOVA (time×treatment) in ITT, adjusted for age and sex. Linear regressions between changes in plasma NFL, GFAP, and Tau and changes in OCDS score, adjusted for age and sex.
8. Treatment adherence analysis: linear regression adjusted for age and sex for good adherence (≥45 tablets out of 56) with age, sex, daily alcohol consumption at inclusion, morning withdrawal symptoms, morning alcohol use, active cocaine use, OAT use, EPICES deprivation score, homelessness status, MoCA score, DERS impulsivity subscale, and OCDS score at T1. Multivariate analysis will follow including factors with p≤0.10 in univariate analysis, adjusted for age and sex.
9. Proteome analysis: change in plasma proteins between T1 and T2 compared between thiamine and control groups using repeated-measures ANOVA (time×treatment) in ITT, adjusted for age and sex, with correction for multiple testing.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut National De La Sante Et De La Recherche Medicale

Sponsor organisation

Institut National De La Sante Et De La Recherche Medicale

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Institut National De La Sante Et De La Recherche Medicale

Contact name

Virgile CLERGUE-DUVAL

Public contact point

Organisation

Institut National De La Sante Et De La Recherche Medicale

Contact name

Virgile CLERGUE-DUVAL

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications