Lactobacillus-containing Cultured Milk Drink Alleviates Depression Score Among Adults With Irritable Bowel Syndrome

The Efficacy of Lactobacillus-containing Cultured Milk Drink in Alleviating Subthreshold Depression Among Adults With Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is frequently associated with any form of psychiatric comorbidities including subthreshold or subclinical depression. Modification of gut ecology with probiotics has implicitly improved IBS and depressive symptoms. However, the efficacy of probiotics on IBS with existing subthreshold depression remain elusive. Therefore, the aim of this study is to evaluate the effects of lactobacillus-containing cultured milk drink on depression scores in adults diagnosed with IBS.

Study Overview

• Status: Recruiting
• Conditions: Irritable Bowel Syndrome With Subthreshold Depression
• Intervention / Treatment: Dietary supplement: Placebo cultured milk drink; Dietary supplement: Lactobacillus containing cultured milk drink

Detailed Description

A total of 140 subjects who fulfilled Rome IV criteria for IBS will be recruited from a tertiary medical centre and among public volunteers. The depression status and categories will be assessed using the Centre Epidemiologic Studies Depression Scale Revised questionnaire (CESD-R): normal mood (score<16), or subthreshold depression (score>16). The subjects are randomised and blinded into four groups: Group A (Normal mood with placebo, n=35), Group B (Normal mood with probiotics, n=35), Group C (Subthreshold depression with placebo, n=35) and Group D (Subthreshold depression with probiotics, n=35). The subjects will be instructed to consume two bottles of cultured milk drink daily for 12 weeks. The probiotic cultured milk drinks contained 10^9 cfu L. CASEI-01 and LA-5. The severity of depression will be measured using Patient Health Questionnaire (PHQ-9) at pre- and post-12-week intervention. Secondary outcome on IBS symptoms severity will be assessed with IBS Symptoms Severity Score (IBS-SSS) and IBS Quality of Life (IBS-QOL).

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Prof. Dr. Norfilza Mohd Mokhtar; Phone Number: +60391458424; Email: norfilza@ppukm.ukm.edu.my
• Study Contact Backup: Name: Prof. Dr. Raja Affendi Raja Ali; Phone Number: +60391455022; Email: draffendi@ppukm.ukm.edu.my

Study Locations

• Malaysia
  • Kuala Lumpur
    • Bandar Tun Razak, Kuala Lumpur, Malaysia, 56000
      • Recruiting
      • Universiti Kebangsaan Malaysia
      • Contact: Prof. Dr. Norfilza Mohd Mokhtar; Phone Number: +60391458424; Email: norfilza@ppukm.ukm.edu.my
      • Contact: Prof. Dr. Raja Affendi Raja Ali; Phone Number: +60391455022; Email: draffendi@ppukm.ukm.edu.my
      • Sub-Investigator: Marlynna Sarkawi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 to 65 years old,
• Meet ROME IV criteria for irritable bowel syndrome,
• Consented to participate in the study.

Exclusion Criteria:

• Lactose intolerance,
• Gastrointestinal disorders such as inflammatory bowel diseases, liver diseases, pancreatic diseases or malignancies,
• Any neurological diseases or malignancies,
• Pregnant and lactating mothers,
• Any metabolic diseases such as hypertension, hypercholesterolaemia, diabetes mellitus, hyper- and hypothyroidism.
• Known psychiatric diagnoses or/and consume psychotropic drugs,
• Ongoing electroconvulsive therapy (ECT),
• Consumption of antibiotics, probiotics, prebiotics, symbiotics products, laxatives, antispasmodics, and/or anticholinergics who refuse to consent for participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Irritable bowel syndrome with normal mood receiving placebo; A total of 35 patients diagnosed with IBS as per Rome IV criteria who scored CESD-R less than 16 will be supplemented with placebo drinks.	Dietary supplement: Placebo cultured milk drink; The placebo prepared was identical to the probiotic-containing product in terms of color, taste and packaging. However, there is no trace of live microorganism in this product.
ACTIVE_COMPARATOR: Irritable bowel syndrome with normal mood receiving probiotics; A total of 35 patients diagnosed with IBS as per Rome IV criteria who scored CESD-R less than 16 will be given lactobacillus-containing cultured milk drinks.	Dietary supplement: Lactobacillus containing cultured milk drink; Each bottle of 125ml cultured milk drink contains a billion colony forming unit (CFU) Lactobacillus acidophillus (LA-5) and Lactobacillus paracasei (L. CASEI-01). Each patient will be given 2 bottles to consume daily for a period of 12 weeks.
PLACEBO_COMPARATOR: Irritable bowel syndrome with subthreshold depression receiving placebo; A total of 35 patients diagnosed with IBS as per Rome IV criteria who scored CESD-R of 16 or above will be supplemented with placebo drinks.	Dietary supplement: Placebo cultured milk drink; The placebo prepared was identical to the probiotic-containing product in terms of color, taste and packaging. However, there is no trace of live microorganism in this product.
EXPERIMENTAL: Irritable bowel syndrome with subthreshold depression receiving probiotics; A total of 35 patients diagnosed with IBS as per Rome IV criteria who scored CESD-R of 16 or above will be given lactobacillus-containing cultured milk drinks.	Dietary supplement: Lactobacillus containing cultured milk drink; Each bottle of 125ml cultured milk drink contains a billion colony forming unit (CFU) Lactobacillus acidophillus (LA-5) and Lactobacillus paracasei (L. CASEI-01). Each patient will be given 2 bottles to consume daily for a period of 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression score	The Centre for Epidemiologic Studies Depression Scale Revised Version (CESD-R) will be used to classify the patients according to their depression status.	12 weeks
Depression severity scale	The Patient Health Questionnaire-9 (PHQ-9) will be used to assess the severity scale for the patients.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life score	The life quality of patients will be measured using the Irritable bowel syndrome Quality of Life Questionnaire (IBS-QOL).	12 weeks
IBS severity score	Any changes in gastrointestinal symptoms severity related to IBS will be quantify using the Irritable bowel syndrome Severity Scoring System (IBS-SSS).	12 weeks
Acute stress biomarker	Morning blood sample will be collected to measure serum cortisol level among patients with IBS.	12 weeks
Depression biomarker	Blood samples collected will be analysed to measure the serum serotonin level of patients with IBS.	12 weeks

Collaborators and Investigators

• Sponsor: National University of Malaysia
• Collaborators: Cotra Enterprises Sdn. Bhd.
• Investigators: Principal Investigator: Prof. Dr. Raja Affendi Raja Ali, Gastroenterology Unit, Faculty of Medicine, Universiti Kebangsaan Malaysia, Malaysia

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 22, 2019
• Primary Completion (ANTICIPATED): June 30, 2022
• Study Completion (ANTICIPATED): July 31, 2022

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (ACTUAL): March 4, 2022

Study Record Updates

• Last Update Posted (ACTUAL): March 4, 2022
• Last Update Submitted That Met QC Criteria: February 23, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: IBS; probiotics; irritable bowel syndrome; subthreshold depression; subclinical depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Digestive System Diseases; Pathologic Processes; Mood Disorders; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Depression; Depressive Disorder; Syndrome; Irritable Bowel Syndrome
• Other Study ID Numbers: UKM PPI/111/8/JEP-2019-312

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No