Effect of Probiotic on Comorbidity of Depression and Constipation
Primary Purpose
Comorbidity of Depression and Constipation
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Probiotic
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Comorbidity of Depression and Constipation
Eligibility Criteria
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
Sites / Locations
- The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Probiotic
Placebo
Arm Description
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.
Placebo made with only the excipients. The placebo sachet was matched to the study probiotic products for taste, color, and size.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Serum Il-1β
Serum Il-1β levels before and after intervention assessed by ELISA.
Serum Il-6
Serum Il-6 levels before and after intervention assessed by ELISA.
Serum TNF-α
Serum TNF-α levels before and after intervention assessed by ELISA.
Serum cortisol
Serum cortisol levels before and after intervention assessed by ELISA.
Serum Brain-derived neurotrophic factor
Serum Brain-derived neurotrophic factor levels before and after intervention assessed by ELISA.
Serum concentrations of tryptophan metabolites
Serum concentrations of tryptophan metabolites quantified by High-Performance Liquid Chromatography and Mass Spectrometry
Serum concentrations of bile acid
Quantification by High-Performance Liquid Chromatography and Mass Spectrometry
Fecal microbiome
Fecal microbiome measured by next generation sequencing
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.
Full Information
NCT ID
NCT04570072
First Posted
September 22, 2020
Last Updated
September 25, 2020
Sponsor
China Agricultural University
Collaborators
The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
1. Study Identification
Unique Protocol Identification Number
NCT04570072
Brief Title
Effect of Probiotic on Comorbidity of Depression and Constipation
Official Title
Effect of Probiotic on Chinese Patients With Depression and Constipated Comorbidity
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2020 (Anticipated)
Primary Completion Date
June 30, 2021 (Anticipated)
Study Completion Date
December 30, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
China Agricultural University
Collaborators
The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Comorbidity of Depression and Constipation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Probiotic
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo made with only the excipients. The placebo sachet was matched to the study probiotic products for taste, color, and size.
Intervention Type
Dietary Supplement
Intervention Name(s)
Probiotic
Intervention Description
Patients receive the formula probiotic for consecutive 8 weeks ( one sachet per day ).
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Patients receive the placebo identical to probiotic for consecutive 8 weeks ( one sachet per day ).
Primary Outcome Measure Information:
Title
Hamilton Depression Rating Scale
Description
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.
Time Frame
Change from baseline score to intervention measurements at 4 and 8 weeks
Secondary Outcome Measure Information:
Title
Patient Assessment of Constipation Symptom
Description
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.
Time Frame
changes from baseline score to intervention measurements at 4 and 8 weeks
Title
Serum Il-1β
Description
Serum Il-1β levels before and after intervention assessed by ELISA.
Time Frame
changes from baseline level to intervention measurements at 4 and 8 weeks
Title
Serum Il-6
Description
Serum Il-6 levels before and after intervention assessed by ELISA.
Time Frame
changes from baseline level to intervention measurements at 4 and 8 weeks
Title
Serum TNF-α
Description
Serum TNF-α levels before and after intervention assessed by ELISA.
Time Frame
changes from baseline level to intervention measurements at 4 and 8 weeks
Title
Serum cortisol
Description
Serum cortisol levels before and after intervention assessed by ELISA.
Time Frame
changes from baseline level to intervention measurements at 4 and 8 weeks
Title
Serum Brain-derived neurotrophic factor
Description
Serum Brain-derived neurotrophic factor levels before and after intervention assessed by ELISA.
Time Frame
changes from baseline level to intervention measurements at 4 and 8 weeks
Title
Serum concentrations of tryptophan metabolites
Description
Serum concentrations of tryptophan metabolites quantified by High-Performance Liquid Chromatography and Mass Spectrometry
Time Frame
Changes from baseline level to intervention measurements at 4 and 8 weeks
Title
Serum concentrations of bile acid
Description
Quantification by High-Performance Liquid Chromatography and Mass Spectrometry
Time Frame
Changes from baseline level to intervention measurements at 4 and 8 weeks
Title
Fecal microbiome
Description
Fecal microbiome measured by next generation sequencing
Time Frame
Changes from baseline to intervention measurements at 4 and 8 weeks
Title
Stool form
Description
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.
Time Frame
Change from baseline score to intervention measurements at 4 and 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fazheng Ren, PhD
Phone
+86-10-62736344
Email
renfazheng@cau.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Xifan Wang, PHD
Email
wangxfan@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fazhen Ren, PhD
Organizational Affiliation
China Agricultural University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210001
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Min Ni, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21791035
Citation
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.
Results Reference
background
PubMed Identifier
1531168
Citation
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.
Results Reference
background
PubMed Identifier
27814521
Citation
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.
Results Reference
background
PubMed Identifier
26218677
Citation
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.
Results Reference
background
PubMed Identifier
27288567
Citation
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.
Results Reference
result
PubMed Identifier
28239408
Citation
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.
Results Reference
result
PubMed Identifier
29731182
Citation
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.
Results Reference
result
PubMed Identifier
26706022
Citation
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.
Results Reference
result
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Effect of Probiotic on Comorbidity of Depression and Constipation
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