Major Depressive DisorderPROMEXNCT03893162
Gut Feeling: Understanding the Mechanisms Underlying the Antidepressant Properties of Probiotics
A study testing Multi-strain probiotic in people with Major Depressive Disorder, run by King's College London at 1 site in United Kingdom.
Trial summary
Previous research has suggested that probiotics can improve depressive symptoms in patients with Major Depressive Disorder (MDD), particularly when used in addition to antidepressants. The aim of this exploratory pilot study is to improve the investigator's understanding of the mechanisms underlying these effects. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Multi-strain probiotic
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jul 2019to 30 Jun 2022
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- aged 18-55;
- currently in a depressive episode according to DSM-5 criteria, who are currently on antidepressant treatment but remain symptomatic (HAM-D17 score >13);
- on stable treatment regimen of an approved treatment for at least 6 weeks;
- non-smokers;
- for participants willing to take part in the neuroimaging component: right-handed, no contraindications, non-claustrophobic, weight <126kg;
- Aged 18-55;
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- No current or historic presence of depression, other psychiatric disorder or substance dependence
- No history of a systemic medical illness;
- No family history of psychiatric disorder;
- Non-smoker;
- Not used probiotic supplements in the past 2 weeks, nor regular use of a probiotic;
- Not used antibiotics in the past 12 weeks;
- No current presence of gastrointestinal disease, or history of major GI surgery;
- No reported regular/current use of antacids, proton pump inhibitors, laxatives, antidiarrheals;
- pregnancy or breastfeeding;
- not currently following a dietary regimen or dietary restrictions unrepresentative of the general population (e.g. fasting or following a specific diet);
Who cannot join
- eating disorder, bipolar disorder, schizophrenia or psychotic symptoms;
- substance dependence in the past year, except for caffeine;
- active suicidal ideation;
- use of probiotic supplements in the past 2 weeks, or regular use of a probiotic;
- use of antibiotics in the past 12 weeks;
- history of allergic reaction to any of the components of BioKult;
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- history of history of a systemic medical illness;
- current presence of significant GI problems or disease or history of major GI surgery;
- pregnancy or breastfeeding;
- following a dietary regimen unrepresentative of the general population (e.g. fasting or following a specific diet);
- regular/current use of antacids, proton pump inhibitors, laxatives, antidiarrheals;
Trial locations and contacts
1 site in 1 country.
About this study
Previous research has suggested that probiotics can improve depressive symptoms in patients with Major Depressive Disorder (MDD), particularly when used in addition to antidepressants. The aim of this exploratory pilot study is to improve the investigator's understanding of the mechanisms underlying these effects. This study will assess the effects of an 8-week double-blind placebo-controlled probiotic intervention on the gut microbiome, inflammatory marker levels, brain activity and neurotransmitter levels in patients with MDD and their relationship to changes in mood. This study will also recruit a group of demographically-matched healthy controls for gut microbiome comparison with the MDD group (non-interventional).
- Conditions
- Major Depressive Disorder
- Being tested
- Multi-strain probiotic, Placebo
- Keywords
- probiotic, depression, microbiome, bacteria
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multi-strain probioticDietary supplement
Also called "BioKult"
The intervention in this study is a multi-strain probiotic which contains:
Bacillus subtilis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Lactobacillus salivarius, Lactococcus lactis ssp. lactis, Streptococcus thermophilus.
Each capsule contains minimum 2 billion live microorganisms per capsule, equivalent to 10 billion live microorganisms per gram.
PlaceboOther
Visually identical capsules in identical packaging containing no active bacteria.
| Study group | Role | What they receive |
|---|---|---|
| Multi-strain probiotic "BioKult" | Experimental | 4 capsules daily for 8 weeks Receives: Dietary Supplement: Multi-strain probiotic |
| Placebo | Placebo comparator | 4 capsules daily for 8 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
gut microbiota in MDD
species diversity and abundance at the level of organisational taxonomic units (OTUs) will be measured with 16S ribosomal RNA (rRNA) sequencing
Measured: baseline
differences in gut microbiota between MDD and healthy volunteers
species diversity and abundance at the level of OTUs will be measured with 16SrRNA-based sequencing and compared between the two groups
Measured: baseline
gut microbiota changes in MDD following probiotic intervention and their correlation to change in depressive symptoms
species diversity and abundance at the level of OTUs will be measured with 16SrRNA-based sequencing and depressive symptoms will be measured with the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Hamilton Depression Rating Scale (HAM-D17)
Measured: change from baseline to week 8
Secondary outcomes (3)
Neurotransmitters
levels of glutamate and gamma-aminobutyric acid (GABA) will be measured with Magnetic Resonance Imaging (MRS)
Measured: change from baseline to week 8
Blood
levels of tumor necrosis factor (TNF-a), interleukins IL-1β, IL-6, IL-17, and C-reactive protein (CRP) will be measured
Measured: change from baseline to week 8
Brain activity
measured with functional magnetic resonance imaging (fMRI)
Measured: change from baseline to week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2019
- Study start1 Jul 2019
- Primary completion29 Jun 2022
- Study completion30 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James M Stone, MBBS PhD FRCPsych, Principal investigator, Institute of Psychiatry Psychology and Neuroscience, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03893162
- Sponsor's protocol ID
- PROMEX
- Acronym
- PROMEX
- Status last verified
- Sep 2021
- First submitted
- 22 Mar 2019
- Last updated
- 30 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Nikolova VL, Cleare AJ, Young AH, Stone JM. Exploring the mechanisms of action of probiotics in depression: Results from a randomized controlled pilot trial. J Affect Disord. 2025 May 1;376:241-250. doi: 10.1016/j.jad.2025.01.153. Epub 2025 Feb 7.
PubMed 39924003Nikolova VL, Cleare AJ, Young AH, Stone JM. Acceptability, Tolerability, and Estimates of Putative Treatment Effects of Probiotics as Adjunctive Treatment in Patients With Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2023 Aug 1;80(8):842-847. doi: 10.1001/jamapsychiatry.2023.1817.
PubMed 37314797
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut Feeling: Understanding the Mechanisms Underlying the Antidepressant Properties of Probiotics
- ClinicalTrials.gov ID
- NCT03893162
- Acronym / sponsor ID
- PROMEX / PROMEX
- Conditions
- Major Depressive Disorder
- Keywords
- probiotic, depression, microbiome, bacteria
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 29 Jun 2022 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 28 Mar 2019 (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.
Previous research has suggested that probiotics can improve depressive symptoms in patients with Major Depressive Disorder (MDD), particularly when used in addition to antidepressants. The aim of this exploratory pilot study is to improve the investigator's understanding of the mechanisms underlying these effects. This study will assess the effects of an 8-week double-blind placebo-controlled probiotic intervention on the gut microbiome, inflammatory marker levels, brain activity and neurotransmitter levels in patients with MDD and their relationship to changes in mood. This study will also recruit a group of demographically-matched healthy controls for gut microbiome comparison with the MDD group (non-interventional).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Multi-strain probiotic "BioKult" | Experimental | Dietary Supplement: Multi-strain probiotic4 capsules daily for 8 weeks |
| Placebo | Placebo comparator | Other: Placebo4 capsules daily for 8 weeks |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- aged 18-55;
- currently in a depressive episode according to DSM-5 criteria, who are currently on antidepressant treatment but remain symptomatic (HAM-D17 score >13);
- on stable treatment regimen of an approved treatment for at least 6 weeks;
- non-smokers;
- for participants willing to take part in the neuroimaging component: right-handed, no contraindications, non-claustrophobic, weight <126kg;
Key exclusion criteria (11 listed)
- eating disorder, bipolar disorder, schizophrenia or psychotic symptoms;
- substance dependence in the past year, except for caffeine;
- active suicidal ideation;
- use of probiotic supplements in the past 2 weeks, or regular use of a probiotic;
- use of antibiotics in the past 12 weeks;
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 |
|---|---|---|
| Multi-strain probioticAlso: "BioKult"The intervention in this study is a multi-strain probiotic which contains: Bacillus subtilis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Lactobacillus salivarius, Lactococcus lactis ssp. lactis, Streptococcus thermophilus. Each capsule contains minimum 2 billion live microorganisms per capsule, equivalent to 10 billion live microorganisms per gram. | Dietary supplement | Multi-strain probiotic "BioKult" |
| PlaceboVisually identical capsules in identical packaging containing no active bacteria. | Other | Placebo |
Primary outcome
gut microbiota in MDD
Time frame: baseline
species diversity and abundance at the level of organisational taxonomic units (OTUs) will be measured with 16S ribosomal RNA (rRNA) sequencing
differences in gut microbiota between MDD and healthy volunteers
Time frame: baseline
species diversity and abundance at the level of OTUs will be measured with 16SrRNA-based sequencing and compared between the two groups
gut microbiota changes in MDD following probiotic intervention and their correlation to change in depressive symptoms
Time frame: change from baseline to week 8
species diversity and abundance at the level of OTUs will be measured with 16SrRNA-based sequencing and depressive symptoms will be measured with the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Hamilton Depression Rating Scale (HAM-D17)
3 secondary outcomes
Neurotransmitters
Time frame: change from baseline to week 8
Blood
Time frame: change from baseline to week 8
Brain activity
Time frame: change from baseline to week 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2022.
- Derived from this study: PubMed 39924003Nikolova VL, Cleare AJ, Young AH, Stone JM. Exploring the mechanisms of action of probiotics in depression: Results from a randomized controlled pilot trial. J Affect Disord. 2025 May 1;376:241-250. doi: 10.1016/j.jad.2025.01.153. Epub 2025 Feb 7.
- Derived from this study: PubMed 37314797Nikolova VL, Cleare AJ, Young AH, Stone JM. Acceptability, Tolerability, and Estimates of Putative Treatment Effects of Probiotics as Adjunctive Treatment in Patients With Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2023 Aug 1;80(8):842-847. doi: 10.1001/jamapsychiatry.2023.1817.
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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.
James M Stone, MBBS PhD FRCPsych principal investigator
Institute of Psychiatry Psychology and Neuroscience, King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multi-strain probiotic in people with Major Depressive Disorder, run by King's College London at 1 site in United Kingdom.
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 16 inclusion and 11 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: finished, as of the sponsor's last update on 30 Jun 2022. 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 United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
gut microbiota in MDD (time frame: baseline). The study lists 3 primary outcomes in all. 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 NCT03893162, which also lists 2 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 Jun 2022.