Riboflavin for Glutamate Reduction in Alcohol Withdrawal
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 主要终点
- Peripheral blood glutamate level, day 6
研究概览
简要总结
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.
详细描述
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. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Riboflavin
Participants in this group will receive 100mg riboflavin TID during study participation.
干预措施: Riboflavin (Drug)
Placebo
Participants in this group will receive inert placebo capsules TID during study participation.
干预措施: Placebo (Other)
结局指标
主要结局
Peripheral blood glutamate level, day 6
时间窗: Will occur on day 6 of the study
measured using high performance liquid chromatography (HPLC)
Peripheral blood glutamate level, day 2
时间窗: Will occur on day 2 of the study
measured using high performance liquid chromatography (HPLC)
Peripheral blood glutamate level, day 8
时间窗: Will occur on day 8 of the study
measured using high performance liquid chromatography (HPLC)
Peripheral blood glutamate level at baseline
时间窗: Will occur on the day of enrollment in the study
measured using high performance liquid chromatography (HPLC)
Peripheral blood glutamate level, day 4
时间窗: Will occur on day 4 of the study
measured using high performance liquid chromatography (HPLC)
Peripheral blood glutamate level, day 10
时间窗: Will occur on day 10 of the study
measured using high performance liquid chromatography (HPLC)
次要结局
- Day 3: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores(Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital))
- Day 7: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores(Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital))
- Day 2: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores(Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital))
- Day 9: Generalized Anxiety Disorder - 7 (GAD7) scale(Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital))
- Baseline: The Alcohol Craving Questionnaire-Revised (ACQ-R)(Will occur on the day of enrollment in the study)
- Day 8: The Alcohol Craving Questionnaire-Revised (ACQ-R)(Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital))
- Day 10: The Daily Assessment of Symptoms -Anxiety (DAS-A)(Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital))
- Day 6: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores(Will occur on the day 6 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(Will occur on the day of enrollment in the study)
- Day 9: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration(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(Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital))
- Baseline Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores(Will occur on the day of enrollment in the study)
- Day 4: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores(Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital))
- Day 8: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores(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(Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital))
- Day 2: # of Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale triggered benzodiazepine administration(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(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(Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital))
- Day 10: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores(Will occur on the day 10 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(Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital))
- Day 3: Generalized Anxiety Disorder - 7 (GAD7) scale(Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital))
- Day 5: Generalized Anxiety Disorder - 7 (GAD7) scale(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(Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital))
- Day 8: Generalized Anxiety Disorder - 7 (GAD7) scale(Will occur on the day 8 after randomization (if participant has not yet discharged from the hospital))
- Day 10: Generalized Anxiety Disorder - 7 (GAD7) scale(Will occur on the day 10 after randomization (if participant has not yet discharged from the hospital))
- Day 7: The Alcohol Craving Questionnaire-Revised (ACQ-R)(Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital))
- Day 4: The Daily Assessment of Symptoms -Anxiety (DAS-A)(Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital))
- Day 6: The Daily Assessment of Symptoms -Anxiety (DAS-A)(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(Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital))
- Day 2: Generalized Anxiety Disorder - 7 (GAD7) scale(Will occur on the day 2 after randomization (if participant has not yet discharged from the hospital))
- Day 2: The Alcohol Craving Questionnaire-Revised (ACQ-R)(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)(Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital))
- Day 10: The Alcohol Craving Questionnaire-Revised (ACQ-R)(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)(Will occur on the day of enrollment in the study)
- Day 2: The Daily Assessment of Symptoms -Anxiety (DAS-A)(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)(Will occur on the day 3 after randomization (if participant has not yet discharged from the hospital))
- Day 7: The Daily Assessment of Symptoms -Anxiety (DAS-A)(Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital))
- Day 5: The Alcohol Craving Questionnaire-Revised (ACQ-R)(Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital))
- Day 9: The Alcohol Craving Questionnaire-Revised (ACQ-R)(Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital))
- Day 4: The Alcohol Craving Questionnaire-Revised (ACQ-R)(Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital))
- Day 6: The Alcohol Craving Questionnaire-Revised (ACQ-R)(Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital))
- Day 5: The Daily Assessment of Symptoms -Anxiety (DAS-A)(Will occur on the day 5 after randomization (if participant has not yet discharged from the hospital))
- Day 8: The Daily Assessment of Symptoms -Anxiety (DAS-A)(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)(Will occur on the day 9 after randomization (if participant has not yet discharged from the hospital))
- Day 5: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale scores(Will occur on the day 5 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(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(Will occur on the day 6 after randomization (if participant has not yet discharged from the hospital))
- Baseline: Generalized Anxiety Disorder - 7 (GAD7) scale(Will occur on the day of enrollment in the study)
- Day 4: Generalized Anxiety Disorder - 7 (GAD7) scale(Will occur on the day 4 after randomization (if participant has not yet discharged from the hospital))
- Day 7: Generalized Anxiety Disorder - 7 (GAD7) scale(Will occur on the day 7 after randomization (if participant has not yet discharged from the hospital))
研究者
Andrew Hughes
Principal Investigator
Oregon Health and Science University