DepressionPhase 2PROMOODNCT05280015
Microbiotherapy in Characterized Depressive Disorder
A Phase 2 study testing microbiotherapy (GynMDD) in people with Depression and Depressive Disorder, run by Centre Hospitalier Universitaire de Besancon at 4 sites in France.
Trial summary
The study aims to evaluate the contribution of a multi-targeted microbiotherapy at 12 weeks in depressed-patients in a situation of failure of a 1st line of antidepressant treatment and treated in add-on with a 2nd antidepressant, venlafaxine. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Depression, Depressive Disorder, Depressive Disorder, Major
- What is being tested?
- microbiotherapy (GynMDD)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 4 sitesFrance
- Study dates
- 8 Jun 2022to Dec 2024
- 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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of unipolar MDD (Diagnostic and Statistical Manual of Mental Disorders V [DSM-V], QIDS-C16≥15)
- No response at a first antidepressant
- under venlafaxine
- Signed informed consent form
- Subjects affiliated to or beneficiary from a French social security regime
Who cannot join
- Contraindications to probiotic administration
- Allergy to one of the compounds of the multi-target probiotic or the placebo
- consuming probiotic-based dietary supplements
- Patient with other psychiatric disorders, except social anxiety disorder, generalized anxiety disorder and nicotine use disorder
- Patient with a serious and/or progressive medical condition, including chronic inflammatory pathologies or autoimmune diseases requiring long-term anti-inflammatory treatment (including corticosteroid therapy) or immunosuppressant.
- Patient with a recent infectious episode likely to require antibiotic therapy.
Show all 14Show fewer
- Patient presenting with a suicidal risk assessed by the suicide item of the QIDS-C16 scale (score item 12 of the QIDS-C16 >2)
- Other concomitant antidepressant and/or lithium and/or anti-inflammatory treatment for the duration of the study
- Subject under measure of protection or guardianship of justice
- Subject beneficiary from a legal protection regime
- Subject unlikely to cooperate or low cooperation stated by investigator
- Subject not covered by social security
- Pregnant woman
- Subject being in the exclusion period of another study or provided for by the "National Volunteer File
Trial locations and contacts
4 sites in 1 country.
France4 sites, 4 recruiting
- Recruiting
Emmanuel HAFFEN
Besançon, 25030
Emmanuel HAFFEN, Prof., +33381219007, emmanuel.haffen@univ-fcomte.fr
Magali NICOLIER, PhD, +33 3 81 21 90 07, mnicolier@chu-besancon.fr
- Not yet recruiting
Centre Hospitalier Spécialisé Charles Perrens
Bordeaux, 33000
Bruno AOUIZERATE, MD PhD, bruno.aouizerate@u-bordeaux.fr
Bruno AOUIZERATE, MD PhD
- Not yet recruiting
CHU de Clermont-Ferrand
Clermont-Ferrand, 63000
Pierre-Michel LLORCA, MD PhD, pmllorca@chu-clermontferrand.fr
Pierre-Michel LLORCA, MD PhD
- Recruiting
Hôpital Henri Mondor / APHP
Créteil, 94000
Marion LEBOYER, MD PhD, marion.leboyer@inserm.fr
Marion LEBOYER, MD PhD
About this study
Official title: A Phase II, Prospective, Multicenter Study Assessing the Contribution and Tolerance of a Multi-targeted Microbiotherapy in Addition to Venlafaxine, After Failure of a First-line Antidepressant Treatment in Depressed Patients
The study aims to evaluate the contribution of a multi-targeted microbiotherapy at 12 weeks in depressed-patients in a situation of failure of a 1st line of antidepressant treatment and treated in add-on with a 2nd antidepressant, venlafaxine.
Read the detailed description
Depression is the most common psychiatric illness and has major personal, societal and economic consequences.
Increase in the disease prevalence is significantly associated with certain somatic pathologies, including metabolic diseases and functional intestinal disorders. From a therapeutic point of view, approximately 2/3 patients are not in remission after first-line antidepressant treatment. Moreover, 20 to 30% patients resist at all the therapeutic strategies classically proposed in this indication.
The identification of new therapeutic strategies is therefore a major challenge, especially for patients with chronic depression resistant to standard treatments.
Various research studies have shown the involvement of inflammatory mechanisms in depression. Thus, the increase in the disease prevalence is significantly associated with certain somatic pathologies, in particular metabolic diseases, a certain number of which are linked to abnormalities of the intestinal microbiota. In this context, the use of probiotics is interesting because some have antidepressant effects, anti-inflammatory and metabolic properties. However, even if a few studies have shown an antidepressant effect of probiotics with improvement of biological markers of inflammation, it seems that the use of probiotics alone is not sufficient for lasting results on depressive symptoms.
The PROMOOD clinical research project fits into this context. We propose to carry out a multicenter clinical study with the product developed by GYNOV (GynMDD® multitarget compound with 3 active ingredients: an amino acid (L-glutamine), an ingredient purified from a plant extract (Cavacurmine) and a probiotic (Lactobacillus rhamnosus GG). In a preclinical study carried out at the CNRS on 144 mice, a synergy of action between these 3 ingredients was demonstrated on the anxio-depressive systems, resulting in an improvement far greater than the expected effect of composition and comparable to a reference injectable antidepressant (clomipramine).
In theses context, the microbiotherapy proposed in this project is very original because:
- a multi-target approach targeting several mechanisms of action: intestinal permeability, glutamine/glutamate/GABA cycle, insulin resistance, immunomodulation, oxidative stress;
- prospect of an optimization/simplification of care;
- It is very acceptable for patients both from the point of view of tolerance and from the economic point of view.
With a phase II, prospective, multicenter design, this study aims to evaluate the contribution and the tolerance of a multi-targeted microbiotherapy in addition to venlafaxine, in a second-line antidepressant treatment. The treatment will be delivered during 12 weeks.
Baseline measures will be compared to those obtained during the treatement administration (every week) and after the treatment administration (every week for the next 12 weeks).
- Conditions
- Depression, Depressive Disorder, Depressive Disorder, Major
- Being tested
- microbiotherapy (GynMDD), placebo
- Keywords
- depression, microbiotherapy
- Medical subject headings
- Depression, Depressive Disorder, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
microbiotherapy (GynMDD)Dietary supplement
multi-target microbiotherapy add-on venlafaxine
placeboOther
placebo add-on venlafaxine
| Study group | Role | What they receive |
|---|---|---|
| Microbiotherapy in addition of venlafaxin | Active comparator | Subjects suffering of MDD and treated by venlafaxine in a second-line assigned to start the microbiotherapy during 12 weeks. The microbiotherapy is GynMDD devlopped by Gynov and which is composed by a probiotic associated to polyphenol and an amino acid. Receives: Dietary Supplement: microbiotherapy (GynMDD) |
| calibration arm | Placebo comparator | Subjects suffering of MDD and treated by venlafaxine in a second-line assigned to start the placebo therapy during 12 weeks. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline Quick Inventory of Depressive Symptomatology (QIDS-C16) at 12 weeks
The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores >/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.
Measured: baseline (Day 0), Week 12 (W12) post-treatment
Secondary outcomes (9)
Change from Severity of depressive symptoms evaluated by the clinician
The QIDS-C16 was derived from specified items in the IDS-C30, clinician-rated scale to assess the severity of a participant's depressive symptoms. Total scores range from 0-27, with a score of 0 indicating no depression and a score of 27 indicating the most severe depression. Negative change from baseline values indicate improvement in the severity of depression.
Measured: baseline (Day 0), at the end of therapy (week 12 (W12)
Change from Severity of depressive symptoms evaluated by the patient
Score achieved on the validated self-reported (QIDS-SR16) evaluating the severity of depressive symptoms. QIDS-SR-16 is a standard questionnaire "The Quick Inventory of Depressive Symptomatology" (16-Item) (Self-Report). This covers questions on falling asleep, sleep during the night, waking up , sleeping too much, feeling sad ,appetite, weight, concentration , how they view themselves, thoughts of death and suicide, general interests, energy levels, feeling slowed down , feeling restless.
Measured: baseline (Day 0), at the end of therapy (week 12 (W12)
Evaluation of treatment observance
A treament observance book was complied by patient during the 12 weeks of therapy
Measured: baseline (Day 0), at the end of therapy (week 12 (W12)
Change from Health related Quality of Life (HrQoL)
HrQOL will be assessed using health status measures of the EuroQuality of Life Five Dimensions (EQ-5D-5L)
Measured: baseline (Day 0), at the end of therapy (week 12 (W12)
Change from anxiety
anxiety assessed using Brief Anxiety Scale of Tyrer (BAS)
Measured: baseline (Day 0), at the end ot therapy (week 12 (W12)
Change from digestive health
digestive evaluation assessed by digestive health scale, scale developped by gastroenterlogists (https://www.worldgastroenterology.org/search?cx=005474681532606414716%3AWMX-367025812\&cof=FORID%3A9\&ie=UTF-8\&q=digestive+health+evaluation)
Measured: baseline (Day 0), at the end ot therapy (week 12 (W12)
Change from serum Inflammatory biological markers
inflammatory inflammatory levels (CRP, Il-1b, Il-6 and TNF-a) in blood samples
Measured: baseline (Day 0), at the end ot therapy (week 12 (W12)
Change from Biological markers of intestinal dysbiosis
zonulin and serobank levels in blood samples
Measured: baseline (Day 0), at the end ot therapy (week 12 (W12)
Change from Metagenomic shotgun sequencing of gut microbiota
preforming metagenomic shotgun sequencing of fecal DNA to determine the changes in the intestinal microbiota composition, diversity and functionality
Measured: baseline (Day 0), at the end ot therapy (week 12 (W12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2022
- Study start8 Jun 2022
- Primary completionJul 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de BesanconThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- After randomization, subjects suffering of MDD and treated by venlafaxine in a second-line assigned to start the microbiotherapy pr placebo during 12 weeks. The microbiotherapy is GynMDD developped by Gynov and which is composed by a probiotic associated to polyphenol and an amino acid.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Besancon
- Sponsor type
- University, hospital or other
- Collaborators
- Fondation FondaMental, GYNOV
- Responsible party
- Sponsor
- Investigators
- Emmanuel HAFFEN, MD PhD, Principal investigator, CHU de Besançon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05280015
- Sponsor's protocol ID
- 2021/621
- Acronym
- PROMOOD
- Status last verified
- Sep 2022
- First submitted
- 18 Feb 2022
- Last updated
- 9 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Prospective, Multicenter Study Assessing the Contribution and Tolerance of a Multi-targeted Microbiotherapy in Addition to Venlafaxine, After Failure of a First-line Antidepressant Treatment in Depressed Patients
- ClinicalTrials.gov ID
- NCT05280015
- Acronym / sponsor ID
- PROMOOD / 2021/621
- Conditions
- Depression, Depressive Disorder, Depressive Disorder, Major
- Keywords
- depression, microbiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de BesanconUniversity, hospital or other
- Collaborators
- Fondation FondaMental, GYNOV
- Study start
- 8 Jun 2022 (actual)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 15 Mar 2022 (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.
The study aims to evaluate the contribution of a multi-targeted microbiotherapy at 12 weeks in depressed-patients in a situation of failure of a 1st line of antidepressant treatment and treated in add-on with a 2nd antidepressant, venlafaxine.
Detailed description
Depression is the most common psychiatric illness and has major personal, societal and economic consequences.
Increase in the disease prevalence is significantly associated with certain somatic pathologies, including metabolic diseases and functional intestinal disorders. From a therapeutic point of view, approximately 2/3 patients are not in remission after first-line antidepressant treatment. Moreover, 20 to 30% patients resist at all the therapeutic strategies classically proposed in this indication.
The identification of new therapeutic strategies is therefore a major challenge, especially for patients with chronic depression resistant to standard treatments.
Various research studies have shown the involvement of inflammatory mechanisms in depression. Thus, the increase in the disease prevalence is significantly associated with certain somatic pathologies, in particular metabolic diseases, a certain number of which are linked to abnormalities of the intestinal microbiota. In this context, the use of probiotics is interesting because some have antidepressant effects, anti-inflammatory and metabolic properties. However, even if a few studies have shown an antidepressant effect of probiotics with improvement of biological markers of inflammation, it seems that the use of probiotics alone is not sufficient for lasting results on depressive symptoms.
The PROMOOD clinical research project fits into this context. We propose to carry out a multicenter clinical study with the product developed by GYNOV (GynMDD® multitarget compound with 3 active ingredients: an amino acid (L-glutamine), an ingredient purified from a plant extract (Cavacurmine) and a probiotic (Lactobacillus rhamnosus GG). In a preclinical study carried out at the CNRS on 144 mice, a synergy of action between these 3 ingredients was demonstrated on the anxio-depressive systems, resulting in an improvement far greater than the expected effect of composition and comparable to a reference injectable antidepressant (clomipramine).
In theses context, the microbiotherapy proposed in this project is very original because:
- a multi-target approach targeting several mechanisms of action: intestinal permeability, glutamine/glutamate/GABA cycle, insulin resistance, immunomodulation, oxidative stress;
- prospect of an optimization/simplification of care;
- It is very acceptable for patients both from the point of view of tolerance and from the economic point of view.
With a phase II, prospective, multicenter design, this study aims to evaluate the contribution and the tolerance of a multi-targeted microbiotherapy in addition to venlafaxine, in a second-line antidepressant treatment. The treatment will be delivered during 12 weeks.
Baseline measures will be compared to those obtained during the treatement administration (every week) and after the treatment administration (every week for the next 12 weeks).
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
- After randomization, subjects suffering of MDD and treated by venlafaxine in a second-line assigned to start the microbiotherapy pr placebo during 12 weeks. The microbiotherapy is GynMDD developped by Gynov and which is composed by a probiotic associated to polyphenol and an amino acid.
| Arm | Type | Receives |
|---|---|---|
| Microbiotherapy in addition of venlafaxin | Active comparator | Dietary Supplement: microbiotherapy (GynMDD)Subjects suffering of MDD and treated by venlafaxine in a second-line assigned to start the microbiotherapy during 12 weeks. The microbiotherapy is GynMDD devlopped by Gynov and which is composed by a probiotic associated to polyphenol and an amino acid. |
| calibration arm | Placebo comparator | Other: placeboSubjects suffering of MDD and treated by venlafaxine in a second-line assigned to start the placebo therapy during 12 weeks. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of unipolar MDD (Diagnostic and Statistical Manual of Mental Disorders V [DSM-V], QIDS-C16≥15)
- No response at a first antidepressant
- under venlafaxine
- Signed informed consent form
- Subjects affiliated to or beneficiary from a French social security regime
Key exclusion criteria (14 listed)
- Contraindications to probiotic administration
- Allergy to one of the compounds of the multi-target probiotic or the placebo
- consuming probiotic-based dietary supplements
- Patient with other psychiatric disorders, except social anxiety disorder, generalized anxiety disorder and nicotine use disorder
- Patient with a serious and/or progressive medical condition, including chronic inflammatory pathologies or autoimmune diseases requiring long-term anti-inflammatory treatment (including corticosteroid therapy) or immunosuppressant.
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 |
|---|---|---|
| microbiotherapy (GynMDD)multi-target microbiotherapy add-on venlafaxine | Dietary supplement | Microbiotherapy in addition of venlafaxin |
| placeboplacebo add-on venlafaxine | Other | calibration arm |
Primary outcome
Change from Baseline Quick Inventory of Depressive Symptomatology (QIDS-C16) at 12 weeks
Time frame: baseline (Day 0), Week 12 (W12) post-treatment
The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores >/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.
9 secondary outcomes
Change from Severity of depressive symptoms evaluated by the clinician
Time frame: baseline (Day 0), at the end of therapy (week 12 (W12)
Change from Severity of depressive symptoms evaluated by the patient
Time frame: baseline (Day 0), at the end of therapy (week 12 (W12)
Evaluation of treatment observance
Time frame: baseline (Day 0), at the end of therapy (week 12 (W12)
Change from Health related Quality of Life (HrQoL)
Time frame: baseline (Day 0), at the end of therapy (week 12 (W12)
Change from anxiety
Time frame: baseline (Day 0), at the end ot therapy (week 12 (W12)
Change from digestive health
Time frame: baseline (Day 0), at the end ot therapy (week 12 (W12)
Change from serum Inflammatory biological markers
Time frame: baseline (Day 0), at the end ot therapy (week 12 (W12)
Change from Biological markers of intestinal dysbiosis
Time frame: baseline (Day 0), at the end ot therapy (week 12 (W12)
Change from Metagenomic shotgun sequencing of gut microbiota
Time frame: baseline (Day 0), at the end ot therapy (week 12 (W12)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2022.
- 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.
Emmanuel HAFFEN, MD PhD principal investigator
CHU de Besançon
4 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 microbiotherapy (GynMDD) in people with Depression and Depressive Disorder, run by Centre Hospitalier Universitaire de Besancon at 4 sites in France.
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 14 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 9 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. 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 Emmanuel HAFFEN, PhD (0033 3 81 21 90 07, emmanuel.haffen@univ-fcomte.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline Quick Inventory of Depressive Symptomatology (QIDS-C16) at 12 weeks (time frame: baseline (Day 0), Week 12 (W12) post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Sep 2022.