Alcohol WithdrawalPhase 2RGRAWNCT04232800
Riboflavin for Glutamate Reduction in Alcohol Withdrawal
A Phase 2 study testing Riboflavin in people with Alcohol Withdrawal and Nutrition Disorders, run by Oregon Health and Science University.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcohol Withdrawal, Nutrition Disorders, Alcohol Use Disorder
- What is being tested?
- Riboflavin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2021to 25 Oct 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
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.
Read the detailed description
General Investigational Plan
Hypotheses:
- 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.
- 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).
- Being tested
- Riboflavin, Placebo
- Keywords
- Glutamate, Riboflavin
- Medical subject headings
- Nutrition Disorders, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiboflavinDrug
Also called Vitamin B2
The intervention will consist of 100mg riboflavin (vitamin B2) given in three time daily dosing.
PlaceboOther
An inert, standard placebo in identical capsules to primary intervention.
| Study group | Role | What they receive |
|---|---|---|
| Riboflavin | Experimental | Participants in this group will receive 100mg riboflavin TID during study participation. Receives: Drug: Riboflavin |
| Placebo | Placebo comparator | Participants in this group will receive inert placebo capsules TID during study participation. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peripheral blood glutamate level at baseline
measured using high performance liquid chromatography (HPLC)
Measured: Will occur on the day of enrollment in the study
Peripheral blood glutamate level, day 2
measured using high performance liquid chromatography (HPLC)
Measured: Will occur on day 2 of the study
Peripheral blood glutamate level, day 4
measured using high performance liquid chromatography (HPLC)
Measured: Will occur on day 4 of the study
Peripheral blood glutamate level, day 6
measured using high performance liquid chromatography (HPLC)
Measured: Will occur on day 6 of the study
Peripheral blood glutamate level, day 8
measured using high performance liquid chromatography (HPLC)
Measured: Will occur on day 8 of the study
Peripheral blood glutamate level, day 10
measured using high performance liquid chromatography (HPLC)
Measured: Will occur on day 10 of the study
Secondary outcomes (50)
Baseline Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
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.
Measured: Will occur on the day of enrollment in the study
Day 2: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
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.
Measured: Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital)
Day 3: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
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.
Measured: Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital)
Day 4: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
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.
Measured: Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital)
Day 5: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
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.
Measured: Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital)
Day 6: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
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.
Measured: Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital)
Day 7: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
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.
Measured: Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital)
Day 8: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
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.
Measured: Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital)
Day 9: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
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.
Measured: Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital)
Day 10: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
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.
Measured: Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital)
Baseline: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
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.
Measured: Will occur on the day of enrollment in the study
Day 2: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
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.
Measured: Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital)
Day 3: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
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.
Measured: Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital)
Day 4: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
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.
Measured: Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital)
Day 5: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
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.
Measured: Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital)
Day 6: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
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.
Measured: Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital)
Day 7: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
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.
Measured: Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital)
Day 8: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
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.
Measured: Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital)
Day 9: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
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.
Measured: Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital)
Day 10: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
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.
Measured: Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital)
Baseline: Generalized Anxiety Disorder - 7 (GAD7) scale
A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.
Measured: Will occur on the day of enrollment in the study
Day 2: Generalized Anxiety Disorder - 7 (GAD7) scale
A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.
Measured: Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital)
Day 3: Generalized Anxiety Disorder - 7 (GAD7) scale
A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.
Measured: Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital)
Day 4: Generalized Anxiety Disorder - 7 (GAD7) scale
A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.
Measured: Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital)
Day 5: Generalized Anxiety Disorder - 7 (GAD7) scale
A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.
Measured: Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital)
Day 6: Generalized Anxiety Disorder - 7 (GAD7) scale
A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.
Measured: Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital)
Day 7: Generalized Anxiety Disorder - 7 (GAD7) scale
A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.
Measured: Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital)
Day 8: Generalized Anxiety Disorder - 7 (GAD7) scale
A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.
Measured: Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital)
Day 9: Generalized Anxiety Disorder - 7 (GAD7) scale
A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.
Measured: Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital)
Day 10: Generalized Anxiety Disorder - 7 (GAD7) scale
A standardized measure of anxiety over the previous 2 weeks. Scores range from 0-21, with a higher score indicating more symptoms of anxiety.
Measured: Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital)
Baseline: The Alcohol Craving Questionnaire-Revised (ACQ-R)
A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings
Measured: Will occur on the day of enrollment in the study
Day 2: The Alcohol Craving Questionnaire-Revised (ACQ-R)
A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings
Measured: Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital)
Day 3: The Alcohol Craving Questionnaire-Revised (ACQ-R)
A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings
Measured: Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital)
Day 4: The Alcohol Craving Questionnaire-Revised (ACQ-R)
A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings
Measured: Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital)
Day 5: The Alcohol Craving Questionnaire-Revised (ACQ-R)
A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings
Measured: Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital)
Day 6: The Alcohol Craving Questionnaire-Revised (ACQ-R)
A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings
Measured: Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital)
Day 7: The Alcohol Craving Questionnaire-Revised (ACQ-R)
A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings
Measured: Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital)
Day 8: The Alcohol Craving Questionnaire-Revised (ACQ-R)
A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings
Measured: Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital)
Day 9: The Alcohol Craving Questionnaire-Revised (ACQ-R)
A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings
Measured: Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital)
Day 10: The Alcohol Craving Questionnaire-Revised (ACQ-R)
A brief, reliable, and validated measure of alcohol craving. Scores range from 1-7 with higher scores indicating stronger alcohol cravings
Measured: Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital)
Baseline: The Daily Assessment of Symptoms -Anxiety (DAS-A)
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
Measured: Will occur on the day of enrollment in the study
Day 2: The Daily Assessment of Symptoms -Anxiety (DAS-A)
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
Measured: Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital)
Day 3: The Daily Assessment of Symptoms -Anxiety (DAS-A)
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
Measured: Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital)
Day 4: The Daily Assessment of Symptoms -Anxiety (DAS-A)
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
Measured: Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital)
Day 5: The Daily Assessment of Symptoms -Anxiety (DAS-A)
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
Measured: Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital)
Day 6: The Daily Assessment of Symptoms -Anxiety (DAS-A)
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
Measured: Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital)
Day 7: The Daily Assessment of Symptoms -Anxiety (DAS-A)
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
Measured: Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital)
Day 8: The Daily Assessment of Symptoms -Anxiety (DAS-A)
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
Measured: Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital)
Day 9: The Daily Assessment of Symptoms -Anxiety (DAS-A)
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
Measured: Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital)
Day 10: The Daily Assessment of Symptoms -Anxiety (DAS-A)
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
Measured: Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start1 Dec 2021 (estimated)
- Primary completion25 Aug 2022 (estimated)
- Study completion25 Oct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol WithdrawalStudies of the same condition, open and under way.
- More trials run by Oregon Health and Science UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to receive either riboflavin or an identical inert placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew Hughes, Oregon Health and Science University
- Investigators
- Brandon Cornejo, MD, PhD, Principal investigator, Oregon Health & Science University, Portland Veterans Health Administration
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04232800
- Sponsor's protocol ID
- RGRAW
- Acronym
- RGRAW
- Status last verified
- Sep 2021
- First submitted
- 13 Jan 2020
- Last updated
- 29 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Riboflavin for Glutamate Reduction in Alcohol Withdrawal
- ClinicalTrials.gov ID
- NCT04232800
- Acronym / sponsor ID
- RGRAW / RGRAW
- Keywords
- Glutamate, Riboflavin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Study start
- 1 Dec 2021 (estimated)
- Primary completion
- 25 Aug 2022 (estimated)
- Study completion
- 25 Oct 2022 (estimated)
- First posted
- 18 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
General Investigational Plan
Hypotheses:
- 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.
- 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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized to receive either riboflavin or an identical inert placebo.
| Arm | Type | Receives |
|---|---|---|
| Riboflavin | Experimental | Drug: RiboflavinParticipants in this group will receive 100mg riboflavin TID during study participation. |
| Placebo | Placebo comparator | Other: PlaceboParticipants in this group will receive inert placebo capsules TID during study participation. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RiboflavinAlso: Vitamin B2The intervention will consist of 100mg riboflavin (vitamin B2) given in three time daily dosing. | Drug | Riboflavin |
| PlaceboAn inert, standard placebo in identical capsules to primary intervention. | Other | Placebo |
Primary outcome
Peripheral blood glutamate level at baseline
Time frame: Will occur on the day of enrollment in the study
measured using high performance liquid chromatography (HPLC)
Peripheral blood glutamate level, day 2
Time frame: Will occur on day 2 of the study
measured using high performance liquid chromatography (HPLC)
Peripheral blood glutamate level, day 4
Time frame: Will occur on day 4 of the study
measured using high performance liquid chromatography (HPLC)
Peripheral blood glutamate level, day 6
Time frame: Will occur on day 6 of the study
measured using high performance liquid chromatography (HPLC)
Peripheral blood glutamate level, day 8
Time frame: Will occur on day 8 of the study
measured using high performance liquid chromatography (HPLC)
Peripheral blood glutamate level, day 10
Time frame: Will occur on day 10 of the study
measured using high performance liquid chromatography (HPLC)
50 secondary outcomes
Baseline Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
Time frame: Will occur on the day of enrollment in the study
Day 2: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
Time frame: Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital)
Day 3: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
Time frame: Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital)
Day 4: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
Time frame: Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital)
Day 5: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
Time frame: Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital)
Day 6: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
Time frame: Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital)
Day 7: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
Time frame: Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital)
Day 8: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
Time frame: Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital)
Day 9: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
Time frame: Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital)
Day 10: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores
Time frame: Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital)
Baseline: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
Time frame: Will occur on the day of enrollment in the study
Day 2: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
Time frame: Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital)
Day 3: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
Time frame: Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital)
Day 4: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
Time frame: Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital)
Day 5: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
Time frame: Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital)
Day 6: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
Time frame: Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital)
Day 7: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
Time frame: Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital)
Day 8: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
Time frame: Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital)
Day 9: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
Time frame: Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital)
Day 10: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration
Time frame: Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital)
Baseline: Generalized Anxiety Disorder - 7 (GAD7) scale
Time frame: Will occur on the day of enrollment in the study
Day 2: Generalized Anxiety Disorder - 7 (GAD7) scale
Time frame: Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital)
Day 3: Generalized Anxiety Disorder - 7 (GAD7) scale
Time frame: Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital)
Day 4: Generalized Anxiety Disorder - 7 (GAD7) scale
Time frame: Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital)
Day 5: Generalized Anxiety Disorder - 7 (GAD7) scale
Time frame: Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital)
Day 6: Generalized Anxiety Disorder - 7 (GAD7) scale
Time frame: Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital)
Day 7: Generalized Anxiety Disorder - 7 (GAD7) scale
Time frame: Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital)
Day 8: Generalized Anxiety Disorder - 7 (GAD7) scale
Time frame: Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital)
Day 9: Generalized Anxiety Disorder - 7 (GAD7) scale
Time frame: Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital)
Day 10: Generalized Anxiety Disorder - 7 (GAD7) scale
Time frame: Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital)
Baseline: The Alcohol Craving Questionnaire-Revised (ACQ-R)
Time frame: Will occur on the day of enrollment in the study
Day 2: The Alcohol Craving Questionnaire-Revised (ACQ-R)
Time frame: Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital)
Day 3: The Alcohol Craving Questionnaire-Revised (ACQ-R)
Time frame: Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital)
Day 4: The Alcohol Craving Questionnaire-Revised (ACQ-R)
Time frame: Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital)
Day 5: The Alcohol Craving Questionnaire-Revised (ACQ-R)
Time frame: Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital)
Day 6: The Alcohol Craving Questionnaire-Revised (ACQ-R)
Time frame: Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital)
Day 7: The Alcohol Craving Questionnaire-Revised (ACQ-R)
Time frame: Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital)
Day 8: The Alcohol Craving Questionnaire-Revised (ACQ-R)
Time frame: Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital)
Day 9: The Alcohol Craving Questionnaire-Revised (ACQ-R)
Time frame: Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital)
Day 10: The Alcohol Craving Questionnaire-Revised (ACQ-R)
Time frame: Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2021.
- Individual participant dataSharing planned: No
Related trials for Alcohol Withdrawal
RecruitingPhase 2/3
Effects of Ketone Supplementation on Alcohol Withdrawal and Brain Metabolism in Alcohol Use Disorder
Alcohol Use Disorder, Alcohol Withdrawal
RecruitingPhase 2/3
Cannabidiol as an Adjunct Treatment for Alcohol Withdrawal and Craving
Alcohol Use Disorder (AUD), Withdrawal From Addictive Substance; Detoxification
Not yet recruitingPhase 1/2
Intravenous Acetate as an Adjunctive Treatment for Alcohol Withdrawal in Hospitalized Patients
Alcohol Withdrawal, Alcohol Abstinence
Not yet recruitingPhase 2
Psilocybin-Assisted Psychotherapy for the Treatment of Severe Alcohol Use Disorder
Alcohol Use Disorder
Recruiting
tAN for Substance Use Disorder
Alcohol Use Disorder, Alcohol Abuse
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brandon Cornejo, MD, PhD principal investigator
Oregon Health & Science University, Portland Veterans Health Administration
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Riboflavin in people with Alcohol Withdrawal and Nutrition Disorders, run by Oregon Health and Science University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrew J Hughes, MD (7014711543, andrew.j.hughes.1@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peripheral blood glutamate level at baseline (time frame: Will occur on the day of enrollment in the study). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2021.