Study on Thiamine Supplementation to REduce braiN Injury Associated With Chronic Alcohol Use in Outpatients With Alcohol Use Disorder (STRENA)
Randomised Open-label Pilot Study on Thiamine Supplementation to REduce braiN Injury Associated With Chronic Alcohol Use in Outpatients With Alcohol Use Disorder
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.
연구 개요
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Virgile Clergue-Duval, MD PhD
- 전화번호: 0033140054214
- 이메일: virgile.clergue-duval@aphp.fr
연구 장소
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Île-de-France Region
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Paris, Île-de-France Region, 프랑스, 75010
- Hospital Lariboisière Fernand-Widal
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연락하다:
- Virgile Clergue-Duval, MD, PhD
- 전화번호: 0033140054214
- 이메일: virgile.clergue-duval@aphp.fr
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Patient with moderate to severe alcohol use disorder
- Reported daily consumption of at least 40g of alcohol
- Patients aged 18 to 65
- Urine pregnancy test performed prior to inclusion for women of childbearing age
- 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
Non-inclusion Criteria:
- 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
- Known or suspected allergy to any of the components of the experimental drug Bevitine (thiamine)
- Known or suspected wheat allergy (other than celiac disease)
- Fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase/isomaltase deficiency
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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간섭 없음: 제어
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실험적: Thiamine
Thiamine 500mg twice daily for 14 days |
Thiamine 500mg twice daily for 14 days
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change in plasma NFL between the two arms, in ITT analysis
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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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)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in plasma NFL between the two arms, in PP analysis
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Change in plasma NFL level between the two arms (time x treatment interaction in a repeated measures ANOVA), in per protocol analysis (PP), using the threshold of reported intake of 80% of thiamine tablets as the criterion for good adherence (45 tablets out of 56), adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction with the presence of morning alcohol withdrawal symptoms on plasma NFL change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between the presence of morning alcohol withdrawal symptoms and the treatment in NFL level change (time x treatment x symptom interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction with reported alcohol use in the morning on plasma NFL change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between reported alcohol use in the morning and the treatment in plasma NFL level change (time x treatment x morning alcohol use interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Change in plasma GFAP level between the two arms
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Change in plasma glial fibrillary acidic protein (GFAP) level between the two arms (time x treatment interaction in a repeated ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Change in plasma total tau level between the two arms
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Change in plasma total tau level between the two arms (time x treatment interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Interaction with self-reported daily alcohol intake on plasma NFL change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between the self-reported daily alcohol intake and the treatment in plasma NFL level change (time x treatment x alcohol intake interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction with self-reported use of cocaine or psychostimulants during the treatment period on plasma NFL change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between self-reported use of cocaine or psychostimulants during the treatment period and the treatment in plasma NFL level change (time x treatment x alcohol intake interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction with opioid agonist therapy on plasma NFL change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between currently undergoing opioid agonist therapy (OAT) and the treatment in plasma NFL level change (time x treatment x OAT interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Association between plasma NFL change and alcohol intake change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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The association test in linear regression between plasma NFL level change and self-reported daily alcohol intake change, adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Plasma NFL level at baseline
기간: Baseline
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Associations in linear regression, adjusted on age and sex, of plasma NFL level with:
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Baseline
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Adherence to thiamine treatment
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Associations in linear regression of good adherence to thiamine treatment (taking at least 45 of 56 tablets) with:
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baseline (day 0) and follow-up (on days 14, 15, or 16)
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Montreal Cognitive Assessment (MoCA) at baseline
기간: Baseline
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Associations in linear regression of MoCA with:
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Baseline
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Change in plasma GFAP between the two arms, in PP analysis
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Change in plasma GFAP level between the two arms (time x treatment interaction in a repeated measures ANOVA), in PP, using the threshold of reported intake of 80% of thiamine tablets as the criterion for good adherence (45 tablets out of 56), adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction with the presence of morning alcohol withdrawal symptoms on plasma GFAP change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between the presence of morning alcohol withdrawal symptoms and the treatment in GFAP level change (time x treatment x symptom interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
|
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Interaction with reported alcohol use in the morning on plasma GFAP change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between reported alcohol use in the morning and the treatment in plasma GFAP level change (time x treatment x morning alcohol use interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
|
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Interaction with self-reported daily alcohol intake on plasma GFAP change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between the self-reported daily alcohol intake and the treatment in plasma GFAP level change (time x treatment x alcohol intake interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction with self-reported use of cocaine or psychostimulants during the treatment period on plasma GFAP change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between self-reported use of cocaine or psychostimulants during the treatment period and the treatment in plasma GFAP level change (time x treatment x alcohol intake interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction with opioid agonist therapy on plasma GFAP change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between currently undergoing opioid agonist therapy (OAT) and the treatment in plasma GFAP level change (time x treatment x OAT interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Association between plasma GFAP change and alcohol intake change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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The association test in linear regression between plasma GFAP level change and self-reported daily alcohol intake change, adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Plasma GFAP level at baseline
기간: Baseline
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Associations in linear regression, adjusted on age and sex, of plasma GFAP level with:
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Baseline
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Change in plasma total tau between the two arms, in PP analysis
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
|
Change in plasma total tau level between the two arms (time x treatment interaction in a repeated measures ANOVA), in PP, using the threshold of reported intake of 80% of thiamine tablets as the criterion for good adherence (45 tablets out of 56), adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
|
|
Interaction with the presence of morning alcohol withdrawal symptoms on plasma total tau change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Interaction between the presence of morning alcohol withdrawal symptoms and the treatment in total tau level change (time x treatment x symptom interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
|
|
Interaction with reported alcohol use in the morning on plasma total tau change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
|
Interaction between reported alcohol use in the morning and the treatment in plasma total tau level change (time x treatment x morning alcohol use interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
|
|
Interaction with self-reported daily alcohol intake on plasma total tau change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
|
Interaction between the self-reported daily alcohol intake and the treatment in plasma total tau level change (time x treatment x alcohol intake interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
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 total tau change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
|
Interaction between self-reported use of cocaine or psychostimulants during the treatment period and the treatment in plasma total tau level change (time x treatment x alcohol intake interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
|
|
Interaction with opioid agonist therapy on plasma total tau change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
|
Interaction between currently undergoing opioid agonist therapy (OAT) and the treatment in plasma total tau level change (time x treatment x OAT interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
|
|
Association between plasma total tau change and alcohol intake change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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The association test in linear regression between plasma total tau level change and self-reported daily alcohol intake change, adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Plasma total tau level at baseline
기간: Baseline
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Associations in linear regression, adjusted on age and sex, of plasma total tau level with:
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Baseline
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Proteome analysis
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Changes in plasma proteome between the two arms (time x treatment interaction in a repeated measures ANOVAs), ITT adjusted on sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Change in alcohol craving between the two arms
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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Change in Obsessive Compulsive Drinking Scale score between the two arms (time x treatment interaction in a repeated measures ANOVA), in ITT adjusted for sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Association between plasma NFL change and alcohol craving change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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The association test in linear regression between plasma NFL level change and self-reported OCDS change, adjusted on sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Association between plasma GFAP change and alcohol craving change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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The association test in linear regression between plasma GFAP level change and self-reported OCDS change, adjusted on sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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Association between plasma total tau change and alcohol craving change
기간: baseline (day 0) and follow-up (on days 14, 15, or 16)
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The association test in linear regression between plasma total tau level change and self-reported OCDS change, adjusted on sex and age. |
baseline (day 0) and follow-up (on days 14, 15, or 16)
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공동 작업자 및 조사자
수사관
- 수석 연구원: Virgile Clergue-Duval, MD PhD, Assistance Publique - Hôpitaux de Paris
- 연구 책임자: Florence Vorspan, MD PhD, Inserm UMR-S 1144 Therapeutic optimization in neuropharmacology
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- C25-96
- 2025 (미국 NIH 보조금/계약)
- 2025-524148-36-00 (씨티스)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
미국에서 제조되어 미국에서 수출되는 제품
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