UMIN-CTR Clinical Trial

Public title

The effect of probiotics on depressive symptoms in depressed patients

Acronym

The effect of probiotics on depressive symptoms in depressed patients

Scientific Title

The effect of probiotics on depressive symptoms in depressed patients

Scientific Title:Acronym

The effect of probiotics on depressive symptoms in depressed patients

Region

Japan

Condition

Depression

Classification by specialty

Medicine in general	Neurology	Psychosomatic Internal Medicine
Psychiatry

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Evaluate the effect of probiotics on intestinal flora and depressive symptoms in depressed patients.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

1. Hamilton Depression Rating Scale(HAM-D)
2. Mini-International Neuropsychiatric Interview
3. ROME-III/ IV
4.Distribution of bacterial in feces

Key secondary outcomes

1. Psychometric tests
2. Plasma/Serum hormones
3. Magnetic resonance imaging

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Prevention

Type of intervention

Food

Interventions/Control_1

Intake probiotics for 3 months.
(L. casei YIT 9029)

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

65

years-old

>

Gender

Male and Female

Key inclusion criteria

(1)Depressed patient (HAM-D score more than 11 point).
(2)Subjects showing a sufficient understanding of the clinical trial procedure and agreeing to participate in the study by written informed consent at his own will.
(3)For Japanese who aged 20 or over and under 65 years old when acquiring
(4)Right-handed person

Key exclusion criteria

(1)Subjects who have a history of cardiovascular disease, liver disease, kidney disease, digestive tract disease and diabetes.
(2)Subjects suspected to suffer from alcohol dependence and / or drug dependence.
(3)Subjects who have a specific configuration that occur allergy and / or hypersensitivity against test drinks.
(4)Marked suicidal ideation as indexed by three points or more on the "suicide" item of HAM-D.
(5)Subjects who have edema in the brain.
(6)Subjects who are diagnosed as a complication of dementia or intellectual disability.
(7)Subjects who are lactating and/or pregnant.
(8)Subjects who have a contraindication to MRI, such as claustrophobia, tattoo, implanted electrical device (e.g. cardiac pacemaker).
(9)Those who have suffered serious head trauma or a central nervous system disease.
(10)Subjects who are judged as unfit for the subject by the principal investigator

Target sample size

20

Name of lead principal investigator

1st name	Hiroshi
Middle name
Last name	Kunugi

Organization

National Center of Neurology and Psychiatry

Division name

Department of Mental Disorder Research

Zip code

187-8551

Address

4-1-1 Ogawahigashicho, Kodaira-city, Tokyo, Japan

TEL

042-341-2711

Email

hkunugi@ncnp.go.jp

Name of contact person

1st name	Hiroshi
Middle name
Last name	Kunugi

Organization

National Center of Neurology and Psychiatry

Division name

Department of Mental Disorder Research

Zip code

187-8551

Address

4-1-1 Ogawahigashicho, Kodaira-city, Tokyo, Japan

TEL

042-341-2711

Homepage URL

https://www.ncnp.go.jp/nin/guide/r3/psycho-test/guidance.html

Email

hkunugi@ncnp.go.jp

Institute

National Center of Neurology and Psychiatry

Institute

Department

Personal name

Organization

Yakult Honsha Co., Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

None

Name of secondary funder(s)

None

Organization

Ethics committee of the National Center of Neurology and Psychiatry

Address

4-1-1 Ogawahigashicho, Kodaira-city, Tokyo, Japan

Tel

042-341-2711

Email

rinri-jimu@ncnp.go.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

06

Month

01

Day

URL releasing protocol

https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037429

Publication of results

Published

URL related to results and publications

https://www.mdpi.com/2076-2607/9/5/1026

Number of participants that the trial has enrolled

22

Results

The HAM-D21 score decreased significantly over the intervention period
No statistically significant change for the percentage of subjects diagnosed with IBS.
The counts of total lactobacilli and its subpopulation, Lacticaseibacillus both increased significantly after the intervention. No other bacterial targets were not significantly changed.
Subgroup analyses indicated that greater exposure to Bifidobacterium and the Atopobium cluster was associated with greater reduction of depressive symptoms.

Results date posted

2021

Year

06

Month

04

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Below are baseline characteristics of 18 participants whose data were analyzed.
sex: 14 females and 4males
diagnosis: 15MDD, 3BD
age: 40.6(11.4) years
Education: 15.0(2.2) years
BMI: 21.80(4.22) kg/m^2
HAM-D21 total score: 17.7(4.1)
BDI score: 31.5(11.0)

Participant flow

Initially, a total of 22 participants were enrolled. However, two participants were later excluded due to withdrawal of the informed consent during the study. Of the the 20 participants who completed the study, two who violated the protocol (one used antibotics for Helicobacter pylori eradication, and the other did not submit stool samples) were excluded, leaving 18 participants for the analysis.

Adverse events

No adverse events attributable to the intervention were observed during the study period.

Outcome measures

1. The HAM-D21 total score decreased significantly over the intervention period (0 weeks 17.7(4.1), 12 weeks 10.9(7.3); p < 0.001)
2. The percentage of subjects diagnosed with IBS changed from 38.9% at 0 weeks to 16.7% at 12 weeks, but this change was not statistically significant.
3. The counts of total lactobacilli and its subpopulation, Lacticaseibacillus both increased significantly after the intervention (p < 0.001). No other bacterial targets were not significantly changed.

4. We conducted the responder analysis based on the extent of reduction of depressive symptoms. The subjects whose HAM-D21 score became half the baseline or less were designated as responder (n = 8), and the others as non-responder (n = 10). At baseline (0 weeks), the responders showed significantly higher counts of Bifidobacterium (p < 0.05) and the Atopobium (p < 0.05) cluster than non-responders. To evaluate the relationship between bacterial exposure over the time and reduction of depressive symptoms, we calculated the area under the curve over the 12-week study (AUC_0-12) of the gut microbiota. The AUC_0-12 of both Bifidobacterium and the Atopobium cluster had a significantly negative correlation with the HAM-D21 change (ps < 0.05), indicating that greater exposure to these bacterium was associated with greater reduction of depressive symptoms.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2018

Year

01

Month

05

Day

Date of IRB

2018

Year

01

Month

23

Day

Anticipated trial start date

2018

Year

05

Month

11

Day

Last follow-up date

2019

Year

03

Month

28

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

06

Month

01

Day

Last modified on

2021

Year

06

Month

04

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037429