Riboflavin for Glutamate Reduction in Alcohol Withdrawal

NCT ID: NCT04232800

Last Updated: 2021-09-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-01

Study Completion Date

2022-10-25

Brief Summary

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This RCT intends to investigate the use of oral Riboflavin (Vitamin B2) for reduction of blood glutamate levels in the setting of acute alcohol withdrawal. Participants will be patients admitted to an inpatient hospital unit diagnosed with acute alcohol withdrawal. In addition to receiving care as usual, they will be randomized to receive either 100mg TID riboflavin or an identically dosed placebo. The primary outcome measure will be blood glutamate levels. Secondary outcomes will include measures of alcohol withdrawal and alcohol craving. The investigators hypothesize that those in the riboflavin group will have lower blood levels of glutamate, as well as decreased symptoms of alcohol withdrawal.

Detailed Description

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General Investigational Plan

Hypotheses:

1. Aim 1: Measure the impact of daily oral riboflavin supplementation on blood Glu levels.

Hypothesis 1: Patients receiving riboflavin will have significant reductions in blood Glu levels, as compared to placebo.
2. Aim 2: Observe the impact of oral riboflavin on CIWA-AR scale scoring. Hypothesis 2: Riboflavin will significantly reduce the active group's CIWA-AR scores, and will result in fewer symptom triggered benzodiazepine doses, as compared to placebo.

Plan: The proposed study would apply a recently identified method using vitamin B2 (riboflavin) to reduce excess brain Glu activity in veterans in acute alcohol withdrawal. This method of "glutamate scavenging", was identified in a 2018 as a way to reduce glutamate associated brain damage which typically occurs after stroke. When tested in human patients immediately following stroke, the intervention demonstrated efficacy through better structural and functional outcomes when compared to placebo. Improvements persisted at 3 months after the initial stroke, and were not associated with any known side effects. Administration of riboflavin quickly decreases Glu levels in both the blood and brain, as measured using chromatography and Magnetic Resonance Imaging (MRI), respectively. As riboflavin's Glu reducing properties have just been discovered, this method has only been applied to the treatment of stroke, and has yet to be studied outside of the field of neurology. Further, oral riboflavin has not been investigated as a method of glutamate reduction. The hyperglutamatergic state in patients with alcohol withdrawal provides one opportunity for such an investigation, one that may lead to future studies improving treatments of alcohol withdrawal. Chronic, as well as acute alcohol users have both elevated extracellular glutamate as well as changes to glutamate receptors and transporters. These changes appear play a role in the rewarding effects of alcohol, and contribute to the symptoms of withdrawal. A positive correlation exists between CSF levels of glutamate and the severity of alcohol dependence, and patients in acute withdrawal have measurably increased levels of glutamate in their peripheral blood. During early withdrawal, elevated glutamate levels have been observed in the hippocampus and anterior cingulate cortex, returning to normal 3 days after symptom resolution. Given this information, riboflavin may provide a safe, effective, and affordable intervention to normalize the hyperglutamatergic state associated with alcohol withdrawal. The proposed study would investigate this hypothesis in patients admitted to the inpatient psychiatry unit in acute alcohol withdrawal.

Methods: Participants would be recruited on the inpatient psychiatry unit as they were admitted. The primary teams/on call residents would be asked to page a study member if a patient was admitted on the standard protocol for alcohol withdrawal: the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar). The study coordinator would consent the patient, and they would be randomized to either the placebo or riboflavin group. They would then receive TID oral dosing of either 100mg riboflavin or placebo, in addition to treatment as usual. The primary outcome would be daily blood glutamate levels, obtained with the normal morning labs. Secondary outcomes would CIWA scores, number of symptom-triggered benzodiazepines given, anxiety, and alcohol craving scores (using standardized measures).

Conditions

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Alcohol Withdrawal Nutrition Disorders Alcohol Use Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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Riboflavin

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

Group Type EXPERIMENTAL

Riboflavin

Intervention Type DRUG

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

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Interventions

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Riboflavin

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

Intervention Type DRUG

Placebo

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

Intervention Type OTHER

Other Intervention Names

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Vitamin B2

Eligibility Criteria

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Inclusion Criteria

* Adult veterans ages 18-65
* Admitted to the inpatient psychiatric unit at the Portland VA
* Determine by admitting physician to be currently in or at risk of alcohol withdrawal during admission
* Placed on the CIWA-AR protocol
* Willing to provide informed consent/HIPAA authorization and accept randomization
* Willing to ingest three capsules/day
* Willing to provide daily blood samples H) Fluent in English

Exclusion Criteria

* Known allergy to ingredients of riboflavin, capsules, or placebo ingredients
* Taking any medication acting primarily on Glu receptors (e.g. memantine) or GABA receptors (benzodiazepines) at baseline
* Unable to swallow capsules
* Actively in withdrawal from substances other than alcohol
* Unable to provide full informed consent/HIPAA authorization
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Oregon Health and Science University

OTHER

Sponsor Role lead

Responsible Party

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Andrew Hughes

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Brandon Cornejo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oregon Health & Science University, Portland Veterans Health Administration

Central Contacts

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Andrew J Hughes, MD

Role: CONTACT

7014711543

Other Identifiers

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RGRAW

Identifier Type: -

Identifier Source: org_study_id

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