Clinical trial NCT05280015: Microbiotherapy in Characterized Depressive Disorder
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Depression
Depressive Disorder
Depressive Disorder, Major
Keywords: depression
microbiotherapy
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
Collaborators: name: Fondation FondaMental
name: GYNOV
First posted: 2022-03-15
Enrollment: 92
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.
* 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

Primary outcomes:
measure: Change from Baseline Quick Inventory of Depressive Symptomatology (QIDS-C16) at 12 weeks
timeFrame: baseline (Day 0), Week 12 (W12) post-treatment
Secondary outcomes:
measure: Change from Severity of depressive symptoms evaluated by the clinician
timeFrame: baseline (Day 0), at the end of therapy (week 12 (W12)
measure: Change from Severity of depressive symptoms evaluated by the patient
timeFrame: baseline (Day 0), at the end of therapy (week 12 (W12)
measure: Evaluation of treatment observance
timeFrame: baseline (Day 0), at the end of therapy (week 12 (W12)
measure: Change from Health related Quality of Life (HrQoL)
timeFrame: baseline (Day 0), at the end of therapy (week 12 (W12)
measure: Change from anxiety
timeFrame: baseline (Day 0), at the end ot therapy (week 12 (W12)
measure: Change from digestive health
timeFrame: baseline (Day 0), at the end ot therapy (week 12 (W12)
measure: Change from serum Inflammatory biological markers
timeFrame: baseline (Day 0), at the end ot therapy (week 12 (W12)
measure: Change from Biological markers of intestinal dysbiosis
timeFrame: baseline (Day 0), at the end ot therapy (week 12 (W12)
measure: Change from Metagenomic shotgun sequencing of gut microbiota
timeFrame: baseline (Day 0), at the end ot therapy (week 12 (W12)
Other outcomes:
Locations:
city: Besançon
country: France
facility: Emmanuel HAFFEN
city: Bordeaux
country: France
facility: Centre Hospitalier Spécialisé Charles Perrens
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Créteil
country: France
facility: Hôpital Henri Mondor / APHP
Study officials:
affiliation: CHU de Besançon
name: Emmanuel HAFFEN, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: