Effect of Probiotic on Comorbidity of Depression and Constipation

Effect of Probiotic on Chinese Patients With Depression and Constipated Comorbidity

Depressive disorder, also known as depression, is a type of mood disorder characterized by persistent low mood. The incidence of depression worldwide is about 6%. The high comorbidity rate between depression and constipation indicated the role of the gut-brain axis in depression. Growing evidence suggested that the gut microbiota plays a key role in the development of depression. Probiotics can effectively improve constipation and regulate gut microbiota, and showed potential in alleviating depression. This study investigated the effect of formula probiotic (containing Lactobacillus paracasei, Bifidobacterium animals, Bifidobacterium longum, Bifidobacterium bifidum, and Lactobacillus plantarum) on the comorbidity of depression and constipation.

Study Overview

• Status: Unknown
• Conditions: Comorbidity of Depression and Constipation
• Intervention / Treatment: Dietary supplement: Probiotic; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fazheng Ren, PhD; Phone Number: +86-10-62736344; Email: renfazheng@cau.edu.cn
• Study Contact Backup: Name: Xifan Wang, PHD; Email: wangxfan@126.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210001
      • The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
      • Contact: Min Ni, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Normal body mass index ≥ 18.5 until ≤ 29.9
• Hamilton Rating Scale for Depression (HAMD-17) score not less than 8
• Meet the ROME III criteria for functional constipation
• Agreed to intake study product during the study period
• Agreed to sign written informed consent

Exclusion Criteria:

• Use of systemic antibiotics or antimycotics medication in the 30 days prior to the study
• Investigator's uncertainty about the willingness or ability of subject to comply with the protocol requirements
• Persons with a milk protein allergy, lactose intolerance
• Pregnant or breastfeeding women
• Subject had other serious diseases

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo made with only the excipients. The placebo sachet was matched to the study probiotic products for taste, color, and size.	Dietary supplement: Placebo; Patients receive the placebo identical to probiotic for consecutive 8 weeks ( one sachet per day ).
Experimental: Probiotic; Formula probiotic contains freeze-dried Lactobacillus paracasei, Bifidobacterium animals, Bifidobacterium longum, Bifidobacterium bifidum, and Lactobacillus plantarum, each at a dosage of 3.0 × 10^10 colony forming unit per 2g sachet.	Dietary supplement: Probiotic; Patients receive the formula probiotic for consecutive 8 weeks ( one sachet per day ).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale	Depressive symptoms as measured with the Hamilton Rating Scale for Depression. The score rangs from 0 to 53. The higher score means severer depressive symptoms.	Change from baseline score to intervention measurements at 4 and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Assessment of Constipation Symptom	Constipation symptoms as measured with the Patient Assessment of Constipation Symptom. The score ranges from 0 to 48. The higher score means severer constipated symptoms.	changes from baseline score to intervention measurements at 4 and 8 weeks
Serum Il-1β	Serum Il-1β levels before and after intervention assessed by ELISA.	changes from baseline level to intervention measurements at 4 and 8 weeks
Serum Il-6	Serum Il-6 levels before and after intervention assessed by ELISA.	changes from baseline level to intervention measurements at 4 and 8 weeks
Serum TNF-α	Serum TNF-α levels before and after intervention assessed by ELISA.	changes from baseline level to intervention measurements at 4 and 8 weeks
Serum cortisol	Serum cortisol levels before and after intervention assessed by ELISA.	changes from baseline level to intervention measurements at 4 and 8 weeks
Serum Brain-derived neurotrophic factor	Serum Brain-derived neurotrophic factor levels before and after intervention assessed by ELISA.	changes from baseline level to intervention measurements at 4 and 8 weeks
Serum concentrations of tryptophan metabolites	Serum concentrations of tryptophan metabolites quantified by High-Performance Liquid Chromatography and Mass Spectrometry	Changes from baseline level to intervention measurements at 4 and 8 weeks
Serum concentrations of bile acid	Quantification by High-Performance Liquid Chromatography and Mass Spectrometry	Changes from baseline level to intervention measurements at 4 and 8 weeks
Fecal microbiome	Fecal microbiome measured by next generation sequencing	Changes from baseline to intervention measurements at 4 and 8 weeks
Stool form	Stool form measured with the Bristol Stool Form Scale, which classify the form of human faeces into seven types, successively named type 1 to type 7. Types 1 and 2 indicate constipation, with 3 and 4 being the ideal stools as they are easy to defecate while not containing excess liquid, 5 indicating lack of dietary fiber, and 6 and 7 indicate diarrhoea.	Change from baseline score to intervention measurements at 4 and 8 weeks

Collaborators and Investigators

• Sponsor: China Agricultural University
• Collaborators: The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
• Investigators: Principal Investigator: Fazhen Ren, PhD, China Agricultural University

Publications and helpful links

General Publications

• Sharon G, Sampson TR, Geschwind DH, Mazmanian SK. The Central Nervous System and the Gut Microbiome. Cell. 2016 Nov 3;167(4):915-932. doi: 10.1016/j.cell.2016.10.027.
• Bromet E, Andrade LH, Hwang I, Sampson NA, Alonso J, de Girolamo G, de Graaf R, Demyttenaere K, Hu C, Iwata N, Karam AN, Kaur J, Kostyuchenko S, Lepine JP, Levinson D, Matschinger H, Mora ME, Browne MO, Posada-Villa J, Viana MC, Williams DR, Kessler RC. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 2011 Jul 26;9:90. doi: 10.1186/1741-7015-9-90.
• Aizawa E, Tsuji H, Asahara T, Takahashi T, Teraishi T, Yoshida S, Ota M, Koga N, Hattori K, Kunugi H. Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J Affect Disord. 2016 Sep 15;202:254-7. doi: 10.1016/j.jad.2016.05.038. Epub 2016 May 24.
• Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann Gen Psychiatry. 2017 Feb 20;16:14. doi: 10.1186/s12991-017-0138-2. eCollection 2017. Erratum In: Ann Gen Psychiatry. 2017 Mar 7;16:18.
• Kazemi A, Noorbala AA, Azam K, Eskandari MH, Djafarian K. Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial. Clin Nutr. 2019 Apr;38(2):522-528. doi: 10.1016/j.clnu.2018.04.010. Epub 2018 Apr 24.
• Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi M, Jafari P, Akbari H, Taghizadeh M, Memarzadeh MR, Asemi Z, Esmaillzadeh A. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutrition. 2016 Mar;32(3):315-20. doi: 10.1016/j.nut.2015.09.003. Epub 2015 Sep 28.
• Walker EA, Katon WJ, Jemelka RP, Roy-Bryne PP. Comorbidity of gastrointestinal complaints, depression, and anxiety in the Epidemiologic Catchment Area (ECA) Study. Am J Med. 1992 Jan 24;92(1A):26S-30S. doi: 10.1016/0002-9343(92)90133-v.
• De Palma G, Blennerhassett P, Lu J, Deng Y, Park AJ, Green W, Denou E, Silva MA, Santacruz A, Sanz Y, Surette MG, Verdu EF, Collins SM, Bercik P. Microbiota and host determinants of behavioural phenotype in maternally separated mice. Nat Commun. 2015 Jul 28;6:7735. doi: 10.1038/ncomms8735.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2020
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): September 30, 2020

Study Record Updates

• Last Update Posted (Actual): September 30, 2020
• Last Update Submitted That Met QC Criteria: September 25, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Signs and Symptoms, Digestive; Depression; Depressive Disorder; Constipation
• Other Study ID Numbers: CAUDepression-02

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