Major Depressive DisorderPhase 2NCT04602715
The Safety, Efficacy, and Tolerability of Microbial Ecosystem Therapeutic-2 in People With Major Depression
A Phase 2 study testing MET-2 in people with Major Depressive Disorder and Anxiety, run by NuBiyota at 2 sites in Canada.
Trial summary
To measure the effects of Microbial Ecosystem Therapeutics (MET)-2 on symptoms of depression and anxiety using pre- and post-treatment scores for overall depression and anxiety Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Major Depressive Disorder, Anxiety
- What is being tested?
- MET-2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesCanada
- Study dates
- 1 Apr 2021to Jun 2021
- Phase
- Phase 2
- 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 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Able to provide informed consent.
- Not pregnant
- Willing to participate in follow up as part of the study
- Diagnosis of Major Depressive Disorder (MDD) by the Mini-International Neuropsychiatric Interview (MINI)
- Current depressive episode with a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥15.
- Able to understand and comply with the requirements of the study
- Able to provide stool, urine, and blood samples.
- Those who do not choose to use antidepressants for moderate-severe depression.
Who cannot join
- History of chronic diarrhea
- Need for regular use of agents that affect gastro-intestinal (GI) motility (narcotics such as codeine or morphine, agents such as loperamide or metoclopramide)
- Colostomy
- Elective surgery that will require preoperative antibiotics planned within 6 months of enrolment
- History of bariatric surgery.
- Pregnant, breastfeeding, or planning to get pregnant in the next 6 months
Show all 23Show fewer
- Any condition for which, in the opinion of the investigator, the participant should be excluded from the study.
- Current use of any antidepressant/antianxiety drug (eligible to participate after a 4-week washout period)
- More than three depressive episodes throughout lifetime
- Having failed an anti-depressant treatment during current depressive episode
- Use of any antibiotic drug in the past 4 weeks (may be eligible to participate after a 1-month washout period)
- History of alcohol or substance dependence in the past 6 months
- Daily use of probiotic product in the past 2 weeks (may be eligible to participate after a 2-week washout period)
- Use of any type of laxative in the last 2 weeks.
- Consumption of products fortified in probiotics (may be eligible to participate after a 2-week washout period)
- High suicidal risk, as measured by MADRS item 10 score more than 3
- Current psychotic symptoms
- Bipolar Depression
- History of epilepsy or uncontrolled seizures
- Immunodeficiency (immuno-compromised and immuno-suppressed participants; e.g. acquired immune deficiency syndrome [AIDS], lymphoma, participants undergoing long-term corticosteroid treatment, chemotherapy and allograft participants)
- Unstable medical conditions or serious diseases/conditions (e.g. cancer, cardiovascular, renal, lung, diabetes, psychiatric illness, bleeding disorders, etc.)
- The use of natural health products (NHP); e.g. St. John's Wort, passion flower, etc.) that affect depression
- History of Electroconvulsive therapy (ECT)
Trial locations and contacts
2 sites in 1 country.
Canada2 sites, 2 recruiting
- Recruiting
Providence Care Hospital
Kingston, Ontario, K7L4X3
Cassandra Sgarbossa, BSc, (519) 404-4326, c.sgarbossa@queensu.ca
Roumen Milev, MD, PhD, (613) 544-4900 ext. 73002, milevr@providencecare.ca
- Recruiting
CAMH
Toronto, Ontario, M6J1H4
Ilona Gorbovskaya, MSc, 416 535-8501 ext. 30231, ilona.gorbovskaya@camh.ca
Daniel Mueller, MD/PhD, 416 535-8501 ext. 30851, daniel.mueller@camh.ca
About this study
To measure the effects of Microbial Ecosystem Therapeutics (MET)-2 on symptoms of depression and anxiety using pre- and post-treatment scores for overall depression and anxiety
Read the detailed description
An eight week, randomized, placebo controlled trial to assess subjective changes in mood and anxiety symptoms from baseline to after MET-2 treatment in participants with depression, using MADRS, Hamilton Anxiety Rating Scale (HAM-A), and other mood/anxiety scales and to demonstrate a significantly higher proportion of responders in patient who were randomized to receive the active study drug compared to patients who were randomized to receive placebo.
- Conditions
- Major Depressive Disorder, Anxiety
- Being tested
- MET-2, Placebo
- Medical subject headings
- Depressive Disorder, Major, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MET-2Drug
Subjects will take capsules containing MET-2 daily during the trial. There will be a loading dose at the start of dosing, and a daily dose. There will be a booster dose given at week 2 and a second booster dose taken at week 4 for those subjects who have not improved by that time.
PlaceboDrug
Placebo Control
| Study group | Role | What they receive |
|---|---|---|
| MET-2 20 g | Experimental | Loading dose of MET-2 is administered for the first two days, followed by a regular, daily dose for the duration of the study (6 weeks total).The loading dose will consist of 5 g of MET-2 in the form of ten capsules orally on day one and on day two. The regular daily dose will consist of 1.5 g MET-2 in the form of three MET-2 capsules taken once daily, excluding days where they take the booster (same as loading dose). Receives: Drug: MET-2 |
| Placebo | Placebo comparator | Loading dose of placebo is administered for the first two days, followed by a regular, daily dose of placebo for the duration of the study (6 weeks total).The loading dose will consist of ten capsules of placebo (which match the MET-2 capsules in appearance and weight) taken orally on day one and on day two. The regular daily dose will consist of three placebo capsules taken once daily, excluding days where they take the booster (same as loading dose). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Major Depression Symptoms
To assess subjective changes in mood from baseline to after MET-2 treatment using the Montgomery-Asberg Depression Rating Scale (10 domains given a rating from 0 to 6)
Measured: Baseline vs. Week 6
Change in Anxiety Symptoms
To assess subjective changes in anxiety symptoms from baseline to after MET-2 treatment using the Hamilton Anxiety Rating Scale (14 domains given a rating on a 5 point scale)
Measured: Baseline vs. Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2020
- Study start1 Apr 2021
- Primary completionJun 2021 (estimated)
- Study completionJun 2021 (estimated)
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- two arm, randomized, placebo controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NuBiyota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roumen Milev, MD/PhD, Principal investigator, Queens University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04602715
- Sponsor's protocol ID
- MET-2 301-2
- Status last verified
- Apr 2021
- First submitted
- 9 Oct 2020
- Last updated
- 11 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chinna Meyyappan A, Sgarbossa C, Bromley H, Forth E, Muller DJ, Vazquez G, Cabrera C, Milev R. The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression - A Phase 2, Double-Blind, Placebo-Controlled Study: Clinical Results: Innocuite et efficacite du traitement de l'ecosysteme microbien (met-2) dans la depression majeure - une etude de phase 2 a double insu controlee par placebo : resultats cliniques. Can J Psychiatry. 2025 Nov;70(11):816-823. doi: 10.1177/07067437251328270. Epub 2025 Mar 21.
PubMed 40116713Chinna Meyyappan A, Sgarbossa C, Vazquez G, Bond DJ, Muller DJ, Milev R. The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression: Protocol for a Phase 2, Double-Blind, Placebo-Controlled Study. JMIR Res Protoc. 2021 Sep 22;10(9):e31439. doi: 10.2196/31439.
PubMed 34550085
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety, Efficacy, and Tolerability of Microbial Ecosystem Therapeutic-2 in People With Major Depression
- ClinicalTrials.gov ID
- NCT04602715
- Acronym / sponsor ID
- MET-2 301-2
- Conditions
- Major Depressive Disorder, Anxiety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- NuBiyotaUniversity, hospital or other
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 26 Oct 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.
To measure the effects of Microbial Ecosystem Therapeutics (MET)-2 on symptoms of depression and anxiety using pre- and post-treatment scores for overall depression and anxiety
Detailed description
An eight week, randomized, placebo controlled trial to assess subjective changes in mood and anxiety symptoms from baseline to after MET-2 treatment in participants with depression, using MADRS, Hamilton Anxiety Rating Scale (HAM-A), and other mood/anxiety scales and to demonstrate a significantly higher proportion of responders in patient who were randomized to receive the active study drug compared to patients who were randomized to receive placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- two arm, randomized, placebo controlled
| Arm | Type | Receives |
|---|---|---|
| MET-2 20 g | Experimental | Drug: MET-2Loading dose of MET-2 is administered for the first two days, followed by a regular, daily dose for the duration of the study (6 weeks total).The loading dose will consist of 5 g of MET-2 in the form of ten capsules orally on day one and on day two. The regular daily dose will consist of 1.5 g MET-2 in the form of three MET-2 capsules taken once daily, excluding days where they take the booster (same as loading dose). |
| Placebo | Placebo comparator | Drug: PlaceboLoading dose of placebo is administered for the first two days, followed by a regular, daily dose of placebo for the duration of the study (6 weeks total).The loading dose will consist of ten capsules of placebo (which match the MET-2 capsules in appearance and weight) taken orally on day one and on day two. The regular daily dose will consist of three placebo capsules taken once daily, excluding days where they take the booster (same as loading dose). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Able to provide informed consent.
- Not pregnant
- Willing to participate in follow up as part of the study
- Diagnosis of Major Depressive Disorder (MDD) by the Mini-International Neuropsychiatric Interview (MINI)
- Current depressive episode with a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥15.
Key exclusion criteria (23 listed)
- History of chronic diarrhea
- Need for regular use of agents that affect gastro-intestinal (GI) motility (narcotics such as codeine or morphine, agents such as loperamide or metoclopramide)
- Colostomy
- Elective surgery that will require preoperative antibiotics planned within 6 months of enrolment
- History of bariatric surgery.
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 |
|---|---|---|
| MET-2Subjects will take capsules containing MET-2 daily during the trial. There will be a loading dose at the start of dosing, and a daily dose. There will be a booster dose given at week 2 and a second booster dose taken at week 4 for those subjects who have not improved by that time. | Drug | MET-2 20 g |
| PlaceboPlacebo Control | Drug | Placebo |
Primary outcome
Change in Major Depression Symptoms
Time frame: Baseline vs. Week 6
To assess subjective changes in mood from baseline to after MET-2 treatment using the Montgomery-Asberg Depression Rating Scale (10 domains given a rating from 0 to 6)
Change in Anxiety Symptoms
Time frame: Baseline vs. Week 6
To assess subjective changes in anxiety symptoms from baseline to after MET-2 treatment using the Hamilton Anxiety Rating Scale (14 domains given a rating on a 5 point scale)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2021.
- Derived from this study: PubMed 40116713Chinna Meyyappan A, Sgarbossa C, Bromley H, Forth E, Muller DJ, Vazquez G, Cabrera C, Milev R. The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression - A Phase 2, Double-Blind, Placebo-Controlled Study: Clinical Results: Innocuite et efficacite du traitement de l'ecosysteme microbien (met-2) dans la depression majeure - une etude de phase 2 a double insu controlee par placebo : resultats cliniques. Can J Psychiatry. 2025 Nov;70(11):816-823. doi: 10.1177/07067437251328270. Epub 2025 Mar 21.
- Derived from this study: PubMed 34550085Chinna Meyyappan A, Sgarbossa C, Vazquez G, Bond DJ, Muller DJ, Milev R. The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression: Protocol for a Phase 2, Double-Blind, Placebo-Controlled Study. JMIR Res Protoc. 2021 Sep 22;10(9):e31439. doi: 10.2196/31439.
- Individual participant dataSharing planned: No
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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.
Roumen Milev, MD/PhD principal investigator
Queens University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MET-2 in people with Major Depressive Disorder and Anxiety, run by NuBiyota at 2 sites in Canada.
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 8 inclusion and 23 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 11 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Arthi C Meyyappan, MSc (647.226.2803, meyyappa@providencecare.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Major Depression Symptoms (time frame: Baseline vs. Week 6). The study lists 2 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 NCT04602715, 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 11 May 2021.