8-week of PS128 RCT in Patients With Major Depressive Disorder

Psychophysiological Effects of Lactobacillus Plantarum PS128 in Patients With Major Depressive Disorder :an 8-week Double-blind, Placebo-controlled Trial

Background: Recent studies have suggested that gut-brain axis may be one of the mechanisms of major depression disorder. In animal studies, alteration of gut microbiota can affect animal's depression or anxiety-like behavior, brain neurochemistry and inflammation. In human studies, the composition of gut microbiota is different between patients with MDD and healthy controls. In addition, supplementation of probiotics can improve mood status in community and clinical participants. In preliminary open trial, the investigators found PS-128 can significantly reduce depression severity in patients with MDD. Therefore, the investigators would like to conduct an 8-week randomized, double-blind, placebo controlled trial of PS-128 in patients with MDD.

Aims: This study will be an 8-week randomized, double-blind, placebo-controlled trial to investigate the effects of Lactobacillus plantarum PS128 on psychophysiology in patients with MDD.

Method: This is a two-phase study. In the first phase, the investigators will recruited patients fulfilling the following inclusion criteria: Age 20-65; fulfill Diagnostic and Statistical Manual of Mental Disorders fifth version (DSM-V) criteria of major depressive episode in recent 2 years; Psychotropics including antidepressants, antipsychotics and hypnotics have been kept unchanged for at least 1 months. The exclusion criteria are: comorbid with schizophrenia, bipolar disorder, or other substance use (except tobacco) disorder; having active suicidal or homicidal ideation; known allergy to probiotics; comorbid with diabetes mellitus, irritable bowel syndrome, inflammatory bowl disease, liver cirrhosis, or autoimmune diseases; known active bacterial, fungal, or viral infections in one month; use of antibiotics, steroid, immunosuppressants, probiotics, or synbiotics in the month before collecting blood and fecal samples; pregnant or lactating women; who state to have dietary pattern changed or in diet within previous two months. Those with HAMD-17 >=14 in the first screen will be randomized to PS-128 or placebo, with the ratio of 1:1, in the second phase intervention. In the second phase intervention, the investigators will give eligible patients Lactobacillus plantarum PS128 or placebo for 8 weeks, and compare depression symptoms, gut microbiota, gut permeability, and serum inflammation level before and after intervention.

Study Overview

• Status: Unknown
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Dietary supplement: PS128

Detailed Description

The eligible patients will be randomly assigned to either active (PS128) or identical-appearing placebo capsule in an 1 : 1 ratio. A research assistant who is blind to the status of participants will conduct the randomization allocation. Recruited patients will be randomized in 1:1 ratio, by a computer-generated allocation sequence with blocks of 4. Patients, caregivers, and investigators will be all masked to the assignment. To ensure the concealment of the randomization assignment, active drug and placebo will be provided by coded containers. At the end of the first year, the investigators will temporarily decode the blinded medication to analyze the preliminary results.

Active capsule containing 300 mg of probiotics, equivalent to 3x10^10 CFU of Lactobacillus plantarum PS128. PS128 and placebo will be manufactured by BENED biomedical and packed by a GMP pharmaceutical manufacture. PS128 or placebo will be provided twice, in the morning and in the afternoon, daily. Because activity and diet may alter composition of gut microbiota, the investigators will ask eligible patients not to change their lifestyle or diet pattern. In addition, though effects of psychotropics on inflammation are still controversial (Baumeister et al. 2016b), medications will be kept unchanged during the intervention period. If kinds of psychotropic were changed because of worsening clinical condition, the patient will be withdrawal from the study. However, if only dose of psychotropics were change, the investigators will record the changes, and the patients will be still kept in the study.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chun-Hsin Chen, MD; Phone Number: 886-970-746395; Email: chunhsin57@yahoo.com.tw
• Study Contact Backup: Name: Chun-Hsin Chen, MD; Email: chunhsin57@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 116
    • Recruiting
    • WanFang Hospital, Taipei Medical University
    • Contact: Chun-Hsin Chen, MD; Phone Number: 53961 886-2-29307930; Email: chunhsin57@yahoo.com.tw
    • Principal Investigator: Chun-Hsin Chen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 20-65
2. fulfill Diagnostic and Statistical Manual of Mental Disorders fifth version (DSM-V) criteria of major depressive episode in recent 2 years
3. Psychotropics including antidepressants, antipsychotics and hypnotics have been kept unchanged for at least one month
4. HAMD-17 >= 14

Exclusion Criteria:

1. Comorbid with schizophrenia, bipolar disorder, or other substance use (except tobacco) disorder.
2. having active suicidal or homicidal ideation
3. known allergy to probiotics
4. comorbid with hypertension, diabetes mellitus, irritable bowel syndrome, inflammatory bowl disease, liver cirrhosis, or autoimmune diseases
5. known active bacterial, fungal, or viral infections in one month.
6. use of antibiotics, steroid, immunosuppressants, probiotics, or synbiotics in the month before collecting blood and fecal samples
7. pregnant or lactating women (by history)
8. who obviously change dietary pattern or in diet within previous month

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PS128; PS128 will be given twice daily for 8 weeks Active capsule containing 300 mg of probiotics, equivalent to 3 x10^10 CFU of Lactobacillus plantarum PS128.	Dietary supplement: PS128; PS128 or placebo will be given twice daily for 8 weeks.
Placebo Comparator: placebo; Placebo containing starch will be given twice daily for 8 weeks.	Dietary supplement: PS128; PS128 or placebo will be given twice daily for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of Hamilton Depression Rating Scale- 17 items (HAMD-17)	HAMD-17 to evaluate the severity of depression	baseline, week 2, week 4 and week 8.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of Depression and Somatic Symptoms Scale (DSSS)	DSSS to evaluate the severity of depression	baseline, week 2, week 4 and week 8.
Changes of serum zonulin	use serum zonulin and I-FABP to represent gut permeability	baseline and week 8
Changes of serum IFABP	use serum I-FABP to represent gut permeability	baseline and week 8
Changes of serum hs-CRP level	inflammation markers	baseline and week 8
Changes of serum IL-6 level	inflammation markers	baseline and week 8
Changes of serum IL-10 level	inflammation markers	baseline and week 8
Changes of serum TNF-alpha level	inflammation markers	baseline and week 8
Changes of composition of gut microbiota	The investigators will compare the difference of alpha diversity and relative abundance in phylum level, family level, and genus level before and after 8-week PS128 intervention.	baseline and week 8

Collaborators and Investigators

• Sponsor: Taipei Medical University WanFang Hospital
• Investigators: Principal Investigator: Chun-Hsin Chen, MD, TMU-Wan Fang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2019
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: December 12, 2019
• First Posted (Actual): December 16, 2019

Study Record Updates

• Last Update Posted (Actual): December 19, 2019
• Last Update Submitted That Met QC Criteria: December 17, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: probiotics; inflammation; gut permeability
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: N201906056

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