Clinical trial NCT03314155: Cerebral Neuroinflammation During Major Depressive Episode
Official title: Cerebral Neuroinflammation During Major Depressive Episode: Multicentric Comparative Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Depressive Disorder
Keywords: Depressive disorder
Treatment Resistant Depression
[18 F ] DPA- 714
PET
MRI
Inflammation
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2017-10-19
Enrollment: 60
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: the investigators make the following assumptions: 1) neuroinflammation in MDD can be measured by the \[18 F \] DPA- 714 ; 2) it is accompanied by anatomical and functional changes in the frontal subcortical loops, strongly involved in MDD ; 3) neuroinflammation in patients might be a biomarker related to resistance to treatment in patients with MDD. If this assumptions are validated, then this study will enable a better understanding of the neuroinflammatory processes. This breakthrough could have a long term therapeutic impact, helping to target more specifically antidepressant drugs with anti-inflammatory action and / or drugs targeting neuroinflammation.

Detailed description: The most widespread pathophysiological hypothesis in major depressive disorder (MDD), is the hypothesis of monoamine deficit. The most used antidepressants in everyday clinical practice act by inhibiting the reuptake of monoamines. However, meta-analyzes evaluating the efficacy of antidepressants suggest that they are ineffective in 30 to 40% of patients. Inflammatory mechanisms might be related to the deficiency of monoamines, compromising the effectiveness of conventional antidepressants. Newly developed specific radiotracers allow the use of positron emission tomography (PET) imaging techniques to evaluate neuroinflammation. It has recently demonstrated the relevance of the \[18F\] DPA- 714 as a biomarker of neuroinflammation in humans in several neurological diseases.

Eligibility criteria: * Inclusion criteria for all groups:

  * Written agreement for participation
  * Able to understand instructions and information data
* Inclusion criteria for the experimental group:

  * Responding to MDD criteria (DSM-5)
  * MADRS score\> 20
  * Antidepressant medication considered ineffective and before the introduction of a new treatment according to the recommendations (unchanged dosage for at least a week and plasma levels within the therapeutic range)
* Inclusion criteria for the pathological control group :

  * Having met MDD criteria (DSM-5)
  * In remission for 8 weeks according to the DSM-5
  * MADRS score \<10
  * Treated with antidepressants (unchanged dosage for at least week)
* Inclusion criteria for the control group :

  * Without any neurological or psychiatric previous disorder
  * CRPus \< 5mg/L
* Exclusion criteria for all groups:

  * Patients without public insurance regime.
  * Specific contraindication to the use of MRI (metallic material) or PET (specific allergy related to the ligand).
  * Pregnant and breastfeeding women
  * Persons deprived of liberty by judicial or administrative decision
  * People hospitalized without consent, or subject to legal protection
  * Persons unable to consent
  * Patients with a neurodegenerative disease, bipolar disease, chronic psychotic disorder, addictive disorder, Obsessive Compulsive Disorder, Post-Traumatic Stress disorder (PCL-S\> ou =45), known system pathology
  * Patients with a history of stroke
  * Patients with an acute infectious disease
  * Patients with chronic inflammatory pathology.
  * Patients treated with anti-inflammatory and/or immunosuppressive, and/or antipsychotics, and/or diazepam
* Exclusion criteria for control group:

  * No significant psychiatric or somatic history.
  * No psychotropic treatment
  * Suicidal risk (C-SSRS)
  * Anxiety Disorders (MINI)

Primary outcomes:
measure: distribution pattern of neuroinflammation in Positron Emission Tomography (PET) data
timeFrame: Day 7
Secondary outcomes:
measure: distribution pattern of neuroinflammation in PET data across all groups
timeFrame: Day 7
measure: patients with depressive symptoms and neuroinflammation (i.e. PET data).
timeFrame: Day 7
measure: patients with neuroinflammation (i.e. PET analysis) and MRI parameters for functional and structural integrities.
timeFrame: Day 7
measure: patients with neuroinflammation (i.e. PET analysis) and biological markers of neuroinflammation (i.e. cytokines).
timeFrame: Day 7
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Hôpital de Psychiatrie
state: Midi-Pyrénées
city: Bordeaux
country: France
facility: CHU Bordeaux
state: Nouvelle Aquitaine
city: Montpellier
country: France
facility: CHRU Lapeyronie
state: Occitanie
city: Tours
country: France
facility: Clinique Psychiatrique Universitaire CHRU Tours
state: Val-De-Loire
Study officials:
affiliation: University Hospital, Toulouse
name: Antoine Yrondi, MD PhD
role: PRINCIPAL_INVESTIGATOR
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citation: Yrondi A, Aouizerate B, El-Hage W, Moliere F, Thalamas C, Delcourt N, Sporer M, Taib S, Schmitt L, Arlicot N, Meligne D, Sommet A, Salabert AS, Guillaume S, Courtet P, Galtier F, Mariano-Goulart D, Champfleur NM, Bars EL, Desmidt T, Lemaire M, Camus V, Santiago-Ribeiro MJ, Cottier JP, Fernandez P, Meyer M, Dousset V, Doumy O, Delhaye D, Capuron L, Leboyer M, Haffen E, Peran P, Payoux P, Arbus C. Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study). Front Psychiatry. 2018 Jul 24;9:326. doi: 10.3389/fpsyt.2018.00326. eCollection 2018.