The Efficacy of Probiotic Compared With Placebo Commitment Therapy for Treatment of Major Depressive Disorder

The Efficacy of Probiotic Compared With Placebo and Acceptance and Commitment Therapy for the Treatment of Major Depressive Disorder Among Adult Females

The purpose of this study is to evaluate the efficacy of oral administration of probiotic at 9 log CFU/day as adjunctive treatment in reducing the severity of depression in female patients with major depressive disorder with treatment-as-usual compared to placebo and ACT via the use of questionnaires.

Study Overview

• Status: Withdrawn
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Dietary supplement: Probiotic; Dietary supplement: Placebo; Behavioral: Acceptance and commitment therapy (ACT)

Detailed Description

1. To assess the differences in quality of life among patients on probiotic, placebo and ACT via the use of questionnaire, at 4 timelines (baseline, 6 weeks after starting intervention, 12 weeks after starting intervention, and 24 weeks after starting intervention which is 12 weeks post-termination of intervention).
2. To assess the differences in blood biological markers such as BDNF, TNF-α, IL-6, IL-1β, CRP, and VEGF among patients on probiotic, placebo and ACT via blood biochemical analyses, at 4 timelines (baseline, 6 weeks after starting intervention, 12 weeks after starting intervention, and 24 weeks after starting intervention which is 12 weeks post-termination of intervention).
3. To assess the differences in gut microbiota profiles of patients on probiotic, placebo and ACT via the use of fecal samples, at 3 timelines (baseline, 12 weeks after starting intervention, and 24 weeks after starting intervention which is 12 weeks post-termination of intervention).

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur
    • Cheras, Kuala Lumpur, Malaysia, 56000
      • Hospital Canselor Tuanku Muhriz UKM Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female patient diagnosed with major depressive disorder (confirmed by DSM-5 for depression). There is a strong gender predisposition in depression and anxiety disorders, in which females are more prone to have depressive disorders and anxiety disorders than males. Hence, we will only recruit female patients in this study to control for confounding bias.
• Those with score of more than 8 based on Hamilton Depression Rating Scale (HAMD), indicative of mild to moderate severity of depressive symptoms.
• Age 18 to 35 years old

Exclusion Criteria:

• Pregnant women
• Those who have current and lifetime history of engaging in any psychotherapy
• Those who consumed alcohol and illicit drugs (Heavy or mild)
• Those who has current and lifetime history of other psychiatric illnesses, such as other depressive disorders (persistent depressive disorder, premenstrual dysphoric disorder), anxiety disorders (panic disorder, agoraphobia, generalized anxiety disorder, specific anxiety disorder, and social anxiety disorder), psychotic disorders (schizophrenia, schizophreniform disorder, schizoaffective disorders, brief psychotic disorder, and delusional disorder), bipolar mood disorder, obsessive compulsive disorder, posttraumatic stress disorder, and attention deficit hyperactive disorder, and autism spectrum disorder
• Those who are on medications that can induce psychiatric symptoms, such as cardiovascular agents (clonidine, guanethidine, methyldopa, reserpine, beta blockers), dermatologic agents (isotretinoin), anticonvulsants (levetiracetam), antimigraine medications (triptans), hormonal agents (corticosteroids, oral contraceptives, gonadotropin-releasing hormone agonists, tamoxifen), varenicline, immunological agents (interferons), and levodopa
• Severe gastritis with regular intake omeprazole medication (proton pump inhibitors)
• Women on regular steroid treatment
• Those on long term medication for any illnesses (≥ 6 months)
• Those who are currently on antibiotics or with history of taking antibiotic for the past 2 weeks.
• Those with abnormal full blood count, renal profile, liver function test, fasting blood glucose, fasting lipid profile and ESR (blood collection for all these blood investigations will be carried out in the pre-intervention assessment).
• Patient who has suicidal tendency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic 9 log CFU/day; The intervention consists of daily administration of one sachet/day of probiotic for 12 weeks, where each sachet contains 9 log CFU of probiotic.	Dietary supplement: Probiotic; This project aims to evaluate the efficacy of oral administration of probiotic at 9 log CFU/day as adjunctive treatment in reducing the severity depression in female patients with major depressive disorder with treatment-as-usual compared to placebo and ACT via use of questionnaires.
Placebo Comparator: Placebo; placebo contains primarily carrier and without probiotic. The placebo are identical in taste and appearance and appear as a light-yellow powder.	Dietary supplement: Placebo; This project aims to evaluate the efficacy of oral administration of probiotic at 9 log CFU/day as adjunctive treatment in reducing the severity depression in female patients with major depressive disorder with treatment-as-usual compared to placebo and ACT via use of questionnaires.
Experimental: Acceptance and commitment therapy (ACT); Patients will be provided with ACT for 12 weeks with treatment as usual. The ACT intervention will be conducted in a group of 10 for each session. The ACT modules covered over 12 sessions, 1 hour in each session. The sessions will be held every week	Behavioral: Acceptance and commitment therapy (ACT); Patients will be provided with ACT for 12 weeks with treatment as usual. The ACT intervention will be conducted in a group of 10 for each session. The ACT modules covered over 12 sessions, 1 hour in each session. The sessions will be held every week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
differences in severity of depression in patients with major depressive disorder upon consumption of probiotic at 9 log CFU/day compared to placebo and ACT.	To evaluate differences in severity of depression via the use of the Montgomery and Åsberg (MADRS) Depression Rating Scale questionnaire containing 10-items on a 7-point scale with higher scores indicating more severe depression	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
differences in quality of life in patients with major depressive disorder upon consumption of probiotic at 9 log CFU/day compared to placebo and ACT.	To evaluate differences in quality of life via the use of the RAND-36 questionnaire containing 36-items on a varying point scale including some items with reverse scoring, with higher scores indicating better health status.	24 weeks
differences in blood depression biomarkers in patients with major depressive disorder upon consumption of probiotic at 9 log CFU/day compared to placebo and ACT.	To evaluate differences in depression blood biological markers such as BDNF, TNF-α, IL-6, IL-1β, CRP, and VEGF via measuring concentrations using commercially available ELISA kit.	24 weeks
differences in gut microbiota profiles of patients with major depressive disorder upon consumption of probiotic at 9 log CFU/day compared to placebo and ACT.	To evaluate differences in gut microbiota profiles via microbiota profiling using DNA of fecal samples amplified for bacterial 16S rRNA and analyzed for high-throughput community sequencing.	24 weeks

Collaborators and Investigators

• Sponsor: Min-Tze LIONG
• Collaborators: National University of Malaysia
• Investigators: Study Director: Min Tze Liong, Prof.Dr, School of Industrial Technology, University of Science Malaysia; Principal Investigator: Luke Woon Sy-Cherng, Dr, Department of Psychiatry Hospital Canselor Tuanku Muhriz UKM medical Centre

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Probiotics
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: JEP-2021-606

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