Participants in this group will receive 100mg riboflavin TID during study participation.

Participants in this group will receive inert placebo capsules TID during study participation.

Alcohol Withdrawal

Nutrition Disorders

Alcohol Use Disorder

The intervention will consist of 100mg riboflavin (vitamin B2) given in three time daily dosing.

Riboflavin

An inert, standard placebo in identical capsules to primary intervention.

Placebo

Riboflavin for Glutamate Reduction in Alcohol Withdrawal

measured using high performance liquid chromatography (HPLC)

The CIWA-Ar scale is a measure used in standard of care treatment of alcohol withdrawal. It assesses severity of symptoms, and can be used to determine the need for supportive therapy (e.g. benzodiazepines).It will be collected as standard of care, and will be analyzed as a secondary outcome measure.Scores range from 0-67, with a higher number indicating increased symptoms of alcohol withdrawal.

As part of standard of care for acute alcohol withdrawal, patients are administered benzodiazepines for symptoms if a clinician-determined threshold is met. That is, patients who are more symptomatic (higher CIWA-Ar) scores, receive more benzodiazepines. This data is collected as standard of care, but will be used as a secondary outcome for this study.

A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.

A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings

A reliable and valid measure of anxiety which has been shown to detect reduction of anxiety symptoms within 24 hours. Scores range from 0-80, with a higher score indicating more symptoms of anxiety

Andrew Hughes

Principal Investigator

Oregon Health and Science University

Participants will be randomized to receive either riboflavin or an identical inert placebo.

Treatment and placebo capsules will be identical, and will be identified with each participants unique randomization number provided by the VA pharmacy. This will ensure blinding until study completion. Neither participants nor any study or treatment team members will know the group allocation.

Patients of group I will receive the experimental drug Cytoflavin®, manufactured by POLYSAN (Russia), on the day before surgery, during the surgical intervention, and in the postoperative period. Cytoflavin® solution(Inosine + Nicotinamide + Riboflavin + Succinic Acid) will be administered IV for 7 days, and Cytoflavin® enteric-coated tablets (Inosine + Nicotinamide + Riboflavin + Succinic Acid) will be administered for 25 days (in total 32 days of treatment).

Patients of group II will receive placebo (manufactured by POLYSAN, Russia), on the day before surgery, during the surgical intervention, and in the postoperative period. Placebo solution will be administered IV for 7 days, and placebo enteric-coated tablets will be administered for 25 days (in total 32 days of treatment).

Cognitive Dysfunction

Single drip infusion of 20 ml of Cytoflavin® solution in 200 ml of 0.9%NaCl intravenously once a day

Cytoflavin® solution

2 tablets, orally, with 100 ml of drinking water, 30 minutes before meals, 2 times a day, with an interval of 8-10 hours (but no later than 18:00).

Cytoflavin® enteric-coated tablet

Single drip infusion of 20 ml of placebo solution in 200 ml of 0.9%NaCl intravenously once a day

Placebo solution

Placebo enteric-coated tablet

Regional Clinical Hospital № 3

Central Clinical Hospital with a polyclinic of the Office of the President of the Russian Federation

Alexandrovskaya City Hospital

City Hospital №15

City Hospital №38 named after N.A. Semashko

City Hospital №40 of the Kurortny District

Hospital for War Veterans

I. P. Pavlov 1st St. Petersburg State Medical University

Military Medical Academy named after S.M. Kirov

Pokrovskaya City Hospital

GBUZ YAO "Regional Clinical Hospital"

Research center of specialized types of medical care "Ural Institute of Cardiology"

Ural State Medical University

Efficacy and Safety of Cytoflavin® Used in Elderly Patients for the Prevention of Cognitive Decline After Major Surgery

A Multicentre Double-blind Placebo-controlled Randomized Study of Efficacy and Safety of Cytoflavin®, Intravenous Administration and Enteric-coated Tablets, Used in Elderly Patients for Prevention of Cognitive Decline After Major Surgery

The MoCA test is a one-page 30-point test, ranging between 0 and 30, where 0 is the worst and 30 is the best result; a score of 26-30 or over is considered to be normal. Outcome measure is the change in the MoCA scale score by the end of the treatment course compared with the preoperative score.

MMSE test is a 30-point questionnaire; any score greater than or equal to 24 points (out of 30) indicates a normal cognition; below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment. Outcome measure will be the change of MMSE scale score by the end of the treatment course compared to the preoperative score

MMSE test is a 30-point questionnaire; any score greater than or equal to 24 points (out of 30) indicates a normal cognition; below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment. Outcome measure will be the change of MMSE scale score by the end of the follow-up period

The MoCA test is a one-page 30-point test, ranging between 0 and 30, where 0 is the worst and 30 is the best result; a score of 26-30 or over is considered to be normal. Outcome measure is the change of the MoCA scale score by the end of the follow-up period

MMSE test is a 30-point questionnaire; any score greater than or equal to 24 points (out of 30) indicates a normal cognition; below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment. Outcome measure will be the difference between median group total scores on the MMSE scale.

The MoCA test is a one-page 30-point test, ranging between 0 and 30, where 0 is the worst and 30 is the best result; a score of 26-30 or over is considered to be normal. Outcome measure is the difference in median group values of the MOCA scale

The proportion of patients who developed postoperative delirium in the first 96 hours after surgery according to the results of CAM-ICU

Mortality in the postoperative period in the experimental and control groups

The proportion of patients with a decrease in the results of two or more neuropsychological tests by more than 20% by the end of the treatment course and by the end of the follow-up period compared the baseline values

Change in the overall score for the EQ-5D questionnaire for assessing the quality of life

The proportion of patients dependent in at least two daily functions according to the results of the Katz Daily Activity Index at the end of the treatment course

The group average score by Hospital Anxiety and Depression Scale (HADS) at the end of the treatment course and at the end of the follow-up period. The HADS is a fourteen item scale, a person can score between 0 and 21 for either anxiety or depression, where scores on each scale can be interpreted in ranges: normal (0-7), mild (8-10), moderate (11-14) and severe (15-21).

POLYSAN Scientific & Technological Pharmaceutical Company

Cohort who took part in the cross-sectional study (n=5186)

Cohort who took part in both the cross-sectional and follow-up study (planned n=500 (on-going))

Cardiovascular Disease

Osteoporosis

Alzheimer's Disease

Hypertension

St James's Hospital

Human Intervention Studies Unit, Ulster University

Clinical Translational Research and Innovation Centre (C-TRIC), Altnagelvin Hospital

The Trinity, Ulster and Department of Agriculture Cohort Study

Dual energy x ray absorptiometry (DXA) scan

Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

Hospital Anxiety and Depression Scale (HADS)

Center for Epidemiologic Studies Depression Scale (CES-D)

University of Ulster

University of Dublin, Trinity College

University College Cork

University College Dublin

Ischemic Stroke

Vitamin B2 Streuli®

Solution for injection

Complejo Hospitalario Universitario de Santiago

Administration of CBG000592 (Riboflavin/Vitamin B2) in Patients With Acute Ischemic Stroke

Randomized Clinical Trial to Investigate Whether Administration of CBG000592 (Riboflavin/Vitamin B2) in Patients With Acute Ischemic Stroke Causes a Reduction of Glutamate-mediated Excitotoxicity

Difference between serum glutamate concentration from basal (prior to medication infusion) and levels at 3 ± 1 and 6 ± 1 hours, from administered medication, including branch CBG000592 (riboflavin/vitamin B2) and placebo.

To study the average length of stay in patients with acute ischemic stroke: difference in days, between patient arrival and the patient's discharge, between the two treatment arms.

To study the rate of clinical improvement in patients with acute ischemic stroke: clinical improvement according to the formula: (NIHSSbasal-NIHSSalta) / NIHSSbasal x 100 and compared between the two treatment arms.

Study the functional outcome in patients with acute ischemic stroke: modified Rankin scale at 90 days, between two treatment arms.

Variations of serum glutamate curves in patients with acute ischemic stroke between two branches: all concentrations of serum glutamate.

To explore the prognosis of patients without stroke, evaluating modified Rankin scale at 90 days.

riboflavin/ictus

Riboflavin for Glutamate Reduction in Alcohol Withdrawal

Efficacy and Safety of Cytoflavin® Used in Elderly Patients for the Prevention of Cognitive Decline After Major Surgery

The Trinity, Ulster and Department of Agriculture Cohort Study

Administration of CBG000592 (Riboflavin/Vitamin B2) in Patients With Acute Ischemic Stroke

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