Comorbidity of Depression and ConstipationNCT04570072
Effect of Probiotic on Comorbidity of Depression and Constipation
A study testing Probiotic in people with Comorbidity of Depression and Constipation, run by China Agricultural University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Comorbidity of Depression and Constipation
- What is being tested?
- Probiotic
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2020to 30 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Xifan Wang, PHD contact
China1 site
The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
Nanjing, Jiangsu, 210001
Min Ni, PhD
About this study
Official title: 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.
- Being tested
- Probiotic, Placebo
- Medical subject headings
- Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticDietary supplement
Patients receive the formula probiotic for consecutive 8 weeks ( one sachet per day ).
PlaceboDietary supplement
Patients receive the placebo identical to probiotic for consecutive 8 weeks ( one sachet per day ).
| Study group | Role | What they receive |
|---|---|---|
| Probiotic | Experimental | 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. Receives: Dietary Supplement: Probiotic |
| Placebo | Placebo comparator | Placebo made with only the excipients. The placebo sachet was matched to the study probiotic products for taste, color, and size. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline score to intervention measurements at 4 and 8 weeks
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: changes from baseline level to intervention measurements at 4 and 8 weeks
Serum cortisol
Serum cortisol levels before and after intervention assessed by ELISA.
Measured: 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.
Measured: 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
Measured: 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
Measured: Changes from baseline level to intervention measurements at 4 and 8 weeks
Fecal microbiome
Fecal microbiome measured by next generation sequencing
Measured: 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.
Measured: Change from baseline score to intervention measurements at 4 and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2020
- Study start1 Nov 2020 (estimated)
- Primary completion30 Jun 2021 (estimated)
- Study completion30 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Comorbidity of Depression and ConstipationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- China Agricultural University
- Sponsor type
- University, hospital or other
- Collaborators
- Affiliated Hospital of Nanjing University of Chinese Medicine
- Responsible party
- Principal investigator, Fazheng Ren, China Agricultural University
- Investigators
- Fazhen Ren, PhD, Principal investigator, China Agricultural University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04570072
- Sponsor's protocol ID
- CAUDepression-02
- Status last verified
- Sep 2020
- First submitted
- 22 Sep 2020
- Last updated
- 30 Sep 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21791035Walker 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.
PubMed 1531168Sharon 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.
PubMed 27814521De 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.
PubMed 26218677Aizawa 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.
PubMed 27288567Wallace 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.
PubMed 28239408Kazemi 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.
PubMed 29731182Akkasheh 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.
PubMed 26706022
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Probiotic on Chinese Patients With Depression and Constipated Comorbidity
- ClinicalTrials.gov ID
- NCT04570072
- Acronym / sponsor ID
- CAUDepression-02
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- China Agricultural UniversityUniversity, hospital or other
- Collaborators
- Affiliated Hospital of Nanjing University of Chinese Medicine
- Study start
- 1 Nov 2020 (estimated)
- Primary completion
- 30 Jun 2021 (estimated)
- Study completion
- 30 Dec 2021 (estimated)
- First posted
- 30 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic | Experimental | Dietary Supplement: ProbioticFormula 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 | Placebo comparator | Dietary Supplement: PlaceboPlacebo made with only the excipients. The placebo sachet was matched to the study probiotic products for taste, color, and size. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProbioticPatients receive the formula probiotic for consecutive 8 weeks ( one sachet per day ). | Dietary supplement | Probiotic |
| PlaceboPatients receive the placebo identical to probiotic for consecutive 8 weeks ( one sachet per day ). | Dietary supplement | Placebo |
Primary outcome
Hamilton Depression Rating Scale
Time frame: Change from baseline score to intervention measurements at 4 and 8 weeks
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.
10 secondary outcomes
Patient Assessment of Constipation Symptom
Time frame: changes from baseline score to intervention measurements at 4 and 8 weeks
Serum Il-1β
Time frame: changes from baseline level to intervention measurements at 4 and 8 weeks
Serum Il-6
Time frame: changes from baseline level to intervention measurements at 4 and 8 weeks
Serum TNF-α
Time frame: changes from baseline level to intervention measurements at 4 and 8 weeks
Serum cortisol
Time frame: changes from baseline level to intervention measurements at 4 and 8 weeks
Serum Brain-derived neurotrophic factor
Time frame: changes from baseline level to intervention measurements at 4 and 8 weeks
Serum concentrations of tryptophan metabolites
Time frame: Changes from baseline level to intervention measurements at 4 and 8 weeks
Serum concentrations of bile acid
Time frame: Changes from baseline level to intervention measurements at 4 and 8 weeks
Fecal microbiome
Time frame: Changes from baseline to intervention measurements at 4 and 8 weeks
Stool form
Time frame: Change from baseline score to intervention measurements at 4 and 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2020.
- Background: PubMed 21791035Bromet 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.
- Background: PubMed 1531168Walker 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.
- Background: PubMed 27814521Sharon 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.
- Background: PubMed 26218677De 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 publication: PubMed 27288567Aizawa 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 publication: PubMed 28239408Wallace 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.
- Results publication: PubMed 29731182Kazemi 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 publication: PubMed 26706022Akkasheh 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xifan Wang, PHD contact
Fazhen Ren, PhD principal investigator
China Agricultural University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic in people with Comorbidity of Depression and Constipation, run by China Agricultural University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fazheng Ren, PhD (+86-10-62736344, renfazheng@cau.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Depression Rating Scale (time frame: Change from baseline score to intervention measurements at 4 and 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04570072, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2020.