Effect of Probiotic on Comorbidity of Depression and Constipation

Study Overview
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Brief Summary
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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.

Official Title
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Effect of Probiotic on Chinese Patients With Depression and Constipated Comorbidity

Conditions
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Comorbidity of Depression and Constipation

Intervention / Treatment
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* Dietary Supplement: Probiotic
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>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<br>* Patients receive the formula probiotic for consecutive 8 weeks ( one sachet per day ).<br>|
| Placebo Comparator: Placebo<br>Placebo made with only the excipients. The placebo sachet was matched to the study probiotic products for taste, color, and size. | Dietary Supplement: Placebo<br>* Patients receive the placebo identical to probiotic for consecutive 8 weeks ( one sachet per day ).<br>|

What is the study measuring?
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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 |