The Efficacy of Probiotics for the Treatment of Alcohol Use Disorder Among Adult Males

NCT05830708 | Not Yet Recruiting DMC

• 1 other identifier: XYEFYLL-(research)-2022-28
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

This three-armed, parallel-group, single-blind, multi-center randomized control trial (RCT) aims to evaluate the efficacy of probiotic supplement compared with that of acceptance and commitment therapy (ACT) 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 ACT to mitigate common comorbid of AUD (such as depression and anxiety symptoms); changes in event-related potential (ERP) on electroencephalogram (EEG) monitoring which indicate reduce alcohol craving; and 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, 120 patients diagnosed with AUD (using Diagnostic and Statistical Manual for Mental Disorders 5th Edition or DSM-5) and 120 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, 120 AUD patients will be randomized into three groups of intervention in a 1:1:1 ratio (Lactobacillus sp. probiotic, ACT and placebo group; n = 40 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. While participants in ACT group will undergo training for ACT one session per week for 8 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), changes in ERP on EEG monitoring, and fecal microbiota content.

Conditions

Alcohol Use Disorder

Keywords

probiotics; acceptance and commitment therapy; alcohol use disorder; alcohol craving

Outcome Measures

Primary Outcomes (3)

• Change in Alcohol Use Disorder Identification Test score across four time points

  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.

  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 Clinical Institute Withdrawal Assessment for Alcohol-Revised score across four time points

  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.

  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 Penn Alcohol Craving Scale score across four time points

  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.

  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

Secondary Outcomes (7)

• 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 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 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

Study Arms (3)

Probiotic group

EXPERIMENTAL

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).

Dietary Supplement: Lactobacillus sp. probiotic

Acceptance and commitment therapy (ACT) group

ACTIVE COMPARATOR

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).

Behavioral: Acceptance and commitment therapy

Placebo group

PLACEBO COMPARATOR

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).

Dietary Supplement: Placebo

Interventions

Lactobacillus sp. probiotic DIETARY_SUPPLEMENT

The probiotic product contains good bacteria Lactobacillus sp. and primarily maltodextrin as carrier. Sachets of products containing the probiotic appear as light-yellow powder. The probiotic products are kept at storage temperature range below 30oC according to the condition recommended by the manufacturer.

Probiotic group

Acceptance and commitment therapy BEHAVIORAL

The ACT session is initiated by building good therapeutic rapport with the subject and gather important information such as experiential avoidance, external barriers, fusion past, unworkable actions, and strength of the subject, followed by formulation of the case. The session may began with coaching subjects on acknowledging and accepting their unpleasant thoughts and feelings. The therapy will also focus on defusion to reduce behavioral avoidance of unpleasant thoughts and feelings by acknowledging them but focus on the values identified. Mindfulness is also practice to allow focus onto the present and surrounding to create awareness among the subjects that they are many things in the surrounding which is more enjoyable that we can enjoy rather than making effort to distract or change or avoid the unpleasant thoughts and feelings.

Acceptance and commitment therapy (ACT) group

Placebo DIETARY_SUPPLEMENT

The placebo are in powder form prepare in sachet which is light-yellow in color and should be stored in temperature at below 30oC, which is similar to the appearance of the probiotic. Nevertheless, it contains only maltodextrin in same amount as in the placebo.

Placebo group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Male gender
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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).
• Those who suffer from other mental illnesses (screen by DSM-V criteria).

Sponsors & Collaborators

• Universiti Sains Malaysia: lead
• Xinxiang medical university: collaborator

Related Publications (1)

• Zhang B, Zhang R, Deng H, Cui P, Li C, Yang F, Leong Bin Abdullah MFI. Research protocol of 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. PLoS One. 2023 Dec 5;18(12):e0294768. doi: 10.1371/journal.pone.0294768. eCollection 2023.

  PMID: 38051740 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Acceptance and Commitment Therapy

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cognitive Behavioral Therapy; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Mohammad Farris Iman Leong Bin Abdullah, Dr Psych

  Advanced Medical and Dental Institute, Universiti Sains Malaysia (USM)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohammad Farris Iman Leong Bin Abdullah, Dr Psych

CONTACT

+60186669950; farris@usm.my

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Three-armed, parallel-group, single-blind, multi-center randomized control trial

Study Record Dates

• First Submitted: March 31, 2023
• First Posted: April 26, 2023
• Study Start: May 1, 2023
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: April 26, 2023

Record last verified: 2023-04