The Efficacy of Probiotics for the Treatment of Alcohol Use Disorder Among Adult Males: A Comparison With Placebo and Acceptance and Commitment Therapy in a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Change in Penn Alcohol Craving Scale score across four time points
研究概览
简要总结
This two-armed, parallel-group, double-blind, multi-center randomized control trial (RCT) aims to evaluate the efficacy of probiotic supplement compared with placebo in ameliorating alcohol craving and severity of alcohol use disorder (AUD) in patients diagnosed with AUD after 2 weeks of in-patient detoxification. In addition, this study also compares the efficacy of probiotic supplement and placebo to mitigate common comorbid of AUD (such as depression and anxiety symptoms); depreciate the serum level of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) indicating lowering of systemic inflammation.
In phase I of the study, 28 patients diagnosed with AUD (using Diagnostic and Statistical Manual for Mental Disorders 5th Edition or DSM-5) and 18 healthy controls will be recruited. The measured outcomes to be compared between patients with AUD and healthy non-AUD controls include ERP on EEG monitoring, serum levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and the fecal microbiota content. Then, in phase II of the study, 58 AUD patients will be randomized into two groups of intervention in a 1:1 ratio (Lactobacillus sp. probiotic and placebo group; n = 29 per group). The participants in probiotic and placebo groups will then consumed the Lactobacillus sp. Probiotic and placebo 1 sachet once a day of probiotic and placebo, respectively for 12 weeks. Outcome assessments will be performed across four time points, such as t0 = before intervention began, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention began, and t3 = 24 weeks after intervention began. The primary outcomes to be measured are the degree of alcohol craving, alcohol withdrawal, and severity of alcohol use disorder. While the secondary outcomes to be assessed are severity of comorbid depression and anxiety symptoms, serum levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and fecal microbiota content.
详细描述
The study will be conducted in the Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang, Henan, China and Psychiatric Outpatient Clinic in Advanced Medical and Dental Institute, Universiti Sains Malaysia.
The approval of the study was obtained from the Human Research Ethics Committee of Xinxiang Medical University (code: XYEFYLL-(research)-2022-28) and from the Human Research Ethics Committee of Universiti Sains Malaysia (code: USM/JEPeM/22080546). Prior to participation in the trial, participants will be informed of their right to withdraw from the trial at any time and the data collected will be discarded immediately and will not be used for the study. Participants will be reminded that all personal identifiable information will not be used and only group data will be analyzed and published. They will be assured of their anonymity for participating in the trial. The participants will be assured that the data collected will only be used for research purposes and the findings will not be recorded in their case files. All participants will be assigned a research number for identification purposes, for example "PROB 001". All the data collected from the participants will be stored in the research file which will be locked in a file cabinet, whereby the key will be kept by the principal investigator. Data collected may also be stored in thumb drive and lap top which is only accessible by the research team and the principal investigator.
In order to monitor adverse effect (AE) during the trial, all participants will be given a trial card which contains the name, contact number and email of the members of the research team. They are encouraged to contact the research team member in charge if there is any occurrence of AE. The occurrence of AE will then be reported to the "adverse effect" section of the trial's case report form. The AE which may lead to withdrawal of participants from the trial are: (1) adverse reaction which is not related to the study intervention but cause discomfort to the participants, (2) adverse reaction which is related to the study intervention (probiotic, ACT and/or placebo), and (3) any changes in behavior, temperament, personality, psychotic symptoms, and suicidal tendency that occurred after the study intervention began (probiotic, ACT and/or placebo). All AE should be reported to the Human Research Ethics Committee of Xinxiang Medical University and Universiti Sains Malaysia and investigation should be carried out.
The principal investigator will lead the trial center and will coordinate closely with the research and site coordinators in a day-to-day basis involving in the conduct of the clinical trial, subject recruitment, and data collection. A trial monitoring unit will also be set up which will be chaired by the principal investigator, whereby weekly meeting will be held to discuss on the conduct of the trial, auditing of the trial, and prepare report to be submitted to the Human Ethics Committee of Xinxiang Medical University and Universiti Sains Malaysia. The monitoring of trial data and auditing of the trial will be managed by the clinical trial coordination unit of the 2nd Affiliated Hospital of Xinxiang Medical University and Advanced Medical and Dental Institute, Universiti Sains Malaysia, which are independent of the funder. Interim analysis will be carried out if there is such necessity for premature termination of the trial based on assessment and auditing of the trial data.
Primary objective:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The randomization will be performed by the study statistician, who had no contact with the patients and not involve in the research project. The statistician is trained to randomize subjects who first enrol in the study into the three groups using computer system for randomization purpose. The allocation sequence will not be available to any member of the research team until databases had been completed and locked. Data collection will be performed by research assistants who were not involved in the study and do not know the objectives of the study. While data analysis will be carried out by the statisticians not involved in the study.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •(AUD patients):
- •Hospitalized patients diagnosed with untreated alcohol use disorder (confirmed by the diagnostic criteria of DSM-5).
- •Male, age 18 to 55 years old, Han nationality, junior high school education or above, right-handed.
- •Those with normal eyesight, including corrected vision(screened clinically).
排除标准
- •(AUD patients):
- •The patient suffer from other mental illnesses (screen by DSM-V criteria).
- •The patient has allergy reaction to medications use for conventional treatment of alcohol use disorder.
- •The patient had a history of organic brain disease, a pacemaker, gastrointestinal surgery, or serious health problems.
- •The patient had a history of seizures.
- •The patient is complicated with severe physical disease.
- •Patient has other drug dependence (except for nicotine dependence).
- •The patient took drugs affecting intestinal flora 30 days before and during admission.
- •The patient has participated in any other alcohol-related studies or trials within the past 30 days.
- •Patients had use any prescription or over-the-counter drugs in the past 30 days that may affect mood or alcohol cravings.
- •Inclusion Criteria (controls):
- •Male, age 18 to 55 years old, Han nationality, junior high school education or above, right-handed.
- •No history of psychoactive substance abuse, except tobacco (screen with urine dipstick test).
- •Those with normal eyesight, including corrected vision (screen clinically).
- •No alcoholic beverages in the last 2 weeks.
- •According to the WHO healthy alcohol consumption standard, the average intake of pure alcohol per week is less than 210 grams, or do not drink at all (screen clinically).
- •Exclusion Criteria (controls):
- •Those who suffer from other mental illnesses (screen by DSM-V criteria).
- •Those who has history of organic brain disease, a pacemaker, gastrointestinal surgery, or serious health problems.
- •Those who has history of seizures.
- •Those complicated with severe physical disease.
- •Those with drug dependence, including alcohol dependence (exception for nicotine dependence).
- •Those who took drugs affecting intestinal flora 30 days before and during admission.
- •Those who has participated in any other alcohol-related studies or trials within the past 30 days.
- •Those who use any prescription or over-the-counter drugs in the past 30 days that may affect mood or alcohol cravings.
研究组 & 干预措施
Probiotic group
Probiotics + conventional drug therapy: treatment includes conventional drug therapy* (initial 2 weeks), then probiotics powder 2g, mixed into water or milk, dissolved and oral; 1 sachet per day for 12 weeks
*Conventional drug treatment: alcohol detoxification treatment was carried out at the early stage of admission, mainly with benzodiazepine replacement therapy, while adequate supplementation of B vitamins, strengthening symptomatic supportive treatment, and corresponding antipsychotic drugs, antidepressants or emotional stabilizers were given according to the condition. Benzodiazepines are gradually discontinued after withdrawal symptoms disappear (2 weeks).
干预措施: Lactobacillus sp. probiotic (Dietary Supplement)
Acceptance and commitment therapy (ACT) group
ACT + conventional drug therapy: treatment includes conventional drug therapy* (initial 2 weeks), then 50 minutes, once a week ACT session for 8 weeks (8 sessions).
*Conventional drug treatment: alcohol detoxification treatment was carried out at the early stage of admission, mainly with benzodiazepine replacement therapy, while adequate supplementation of B vitamins, strengthening symptomatic supportive treatment, and corresponding antipsychotic drugs, antidepressants or emotional stabilizers were given according to the condition. Benzodiazepines are gradually discontinued after withdrawal symptoms disappear (2 weeks).
干预措施: Acceptance and commitment therapy (Behavioral)
Placebo group
Placebo + conventional drug therapy: treatment includes conventional drug therapy* (initial 2 weeks), then maltodextrin of the same weight as the test drug treatment group was mixed into water or milk and orally dissolved; 1 sachet per day for 12 weeks.
*Conventional drug treatment: alcohol detoxification treatment was carried out at the early stage of admission, mainly with benzodiazepine replacement therapy, while adequate supplementation of B vitamins, strengthening symptomatic supportive treatment, and corresponding antipsychotic drugs, antidepressants or emotional stabilizers were given according to the condition. Benzodiazepines are gradually discontinued after withdrawal symptoms disappear (2 weeks).
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Change in Penn Alcohol Craving Scale score across four time points
时间窗: At four time points of assessment: t0 (baseline) = before starting intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention began, and t3 = 24 weeks after intervention began
This questionnaire consists of five items to evaluate the severity of craving, including frequency, intensity, duration, difficulty of coping, and average craving degree. The reliability of the Chinese version of PACS was good at Cronbach's α of 0.97. Each item is scored in a seven-point Likert scale from 0 to 6, with 0 being none and 6 being extremely severe. Thus, the total score range from 0 to 30. The higher the total score, the greater is the degree of craving. The subjects will be asked to answer questions according to the situation in the past week.
Change in Alcohol Use Disorder Identification Test score across four time points
时间窗: At four time points of assessment: t0 (baseline) = before starting intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention began, and t3 = 24 weeks after intervention began
This questionnaire can screen drinkers from mild to severe.The reliability and validity of the Chinese version are 0.782. Factor analysis showed that indeed the Chinese version of the AUDIT comprised of three factors and had good convergent and discriminant validity. The scale consists of 10 questions, of which three relate to the amount and frequency of alcohol consumption, three relate to alcohol dependence and four involve in various problems caused by alcohol. The total score range from 0 to 40. The score of the scale ≥ 8 is positive. In general, those with high scores on the first three questions but low scores on the rest suggest serious harmful drinking; High scores in questions 4, 5 and 6 indicate alcohol dependence; High scores in the final section indicate that drinking has caused harm.
Change in Clinical Institute Withdrawal Assessment for Alcohol-Revised score across four time points
时间窗: At four time points of assessment: t0 (baseline) = before starting intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention began, and t3 = 24 weeks after intervention began
The scale is a standard tool for quantifying the severity of alcohol withdrawal symptoms. The reliability of the Chinese version of CIWA-Ar was good with Cronbach's α of 0.83. The total score range from 0 to 30. The total score \< 10 suggests mild withdrawal reaction. The score of 10 to 20 indicates moderate. And the total score of more than 20 is considered severe. A severe total score is associated with a risk of delirium tremens and seizures.
次要结局
- Change in event-related potential in EEG monitoring across four time points(At four time points of assessment: t0 (baseline) = before starting intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention began, and t3 = 24 weeks after intervention began)
- Change in serum tumor necrosis factor-α (in ng/mL) across four time points(At four time points of assessment: t0 (baseline) = before starting intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention began, and t3 = 24 weeks after intervention began)
- Change in serum interleukin-1β (in ng/mL) across across four time points(At four time points of assessment: t0 (baseline) = before starting intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention began, and t3 = 24 weeks after intervention began)
- Change in Hamilton Depression Rating Scale score across four time points(At four time points of assessment: t0 (baseline) = before starting intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention began, and t3 = 24 weeks after intervention began)
- Change in Hamilton Anxiety Rating Scale score across four time points(At four time points of assessment: t0 (baseline) = before starting intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention began, and t3 = 24 weeks after intervention began)
- Change in fecal microbiota analysis across three time points(At three time points of assessment: t0 (baseline) = before starting intervention, t1 = 8 weeks after intervention began, and t2 = 12 weeks after intervention began)
- Change in serum interleukin-6 (in ng/mL) across four time points(At four time points of assessment: t0 (baseline) = before starting intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention began, and t3 = 24 weeks after intervention began)
研究者
Mohammad Farris Iman Leong Bin Abdullah
Principal investigator
Universiti Sains Malaysia