Cerebral neuroinflammation during major depressive episode: multicentric comparative study (InflaDep)

Phase 4

Recruiting

Conditions: Depressive disorder

Registration Number: 2024-518405-18-00

Lead Sponsor: Centre Hospitalier Universitaire De Toulouse

Brief Summary: The primary outcome is to compare TEP data (i.e. distribution pattern of neuroinflammation) between patients with MDD (experimental group), patients who have had a MDD and being in remission for at least 8 weeks, still treated with antidepressants, matched in age and gender with the experimental group (pathological control group) and control subjects, matched in gender and age with both patients’ groups (control group).

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.

Recruitment & Eligibility

Status: Authorised, recruiting

Sex: Not specified

Target Recruitment: 60

Inclusion Criteria

Male or female / age between 18 and 60 years

for the pathological control group : Treated with antidepressants (unchanged dosage for at least week)

for the control group : Without any neurological or psychiatric previous disorder

for the control group : CRPus < 5mg/L

Written agreement for participation

Able to understand instructions and information data

for the experimental group: Responding to MDD criteria (DSM-5)

for the experimental group: MADRS score> 20

for the experimental group: Antidepressant medication considered ineffective and before the introduction of a new treatment according to the recommendations (unchanged dosage for at least 2 week and plasma levels above the lower end of the therapeutic range done after one week more with unchanged dosage).

for the pathological control group : Having met MDD criteria (DSM-5)

for the pathological control group : In remission for 8 weeks according to the DSM-5

for the pathological control group : MADRS score <10

Exclusion Criteria

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, known system pathology

Patients with a history of stroke

Patients with an acute infectious disease

Persons with a phenotype of low affinity to the TSPO tracer

Patients with chronic inflammatory pathology.

Patients treated with anti-inflammatory and/or immunosuppressive, and/or antipsychotics, and/or benzodiazepine

Diabetics

History of documented head trauma

for control group: No significant psychiatric or somatic history.

for control group: No psychotropic treatment

for control group: Suicidal risk (C-SSRS)

for control group: Anxiety Disorders (MINI)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
TSPO density assessed by the cerebral distribution volume of the tracer [18F]DPA-714 in the experimental group versus the control group.		TSPO density assessed by the cerebral distribution volume of the tracer [18F]DPA-714 in the experimental group versus the control group.

Secondary Outcome Measures

Name	Time	Method
the density of the TSPO evaluated by the cerebral distribution volume of the tracer [18F]DPA-714 in the 3 groups (experimental, control and pathological control).		the density of the TSPO evaluated by the cerebral distribution volume of the tracer [18F]DPA-714 in the 3 groups (experimental, control and pathological control).
psychometric scales making it possible to assess the clinical state of subjects: o Depression scale (MADRS) o Anhedonia Scale (SHAPS) o Psychomotor slowing scale (Widlocher scale) o Suicide Risk Rating Scale (CSSRS) o BAS Anxiety Rating Scale (Brief Scale for Anxiety)		psychometric scales making it possible to assess the clinical state of subjects: o Depression scale (MADRS) o Anhedonia Scale (SHAPS) o Psychomotor slowing scale (Widlocher scale) o Suicide Risk Rating Scale (CSSRS) o BAS Anxiety Rating Scale (Brief Scale for Anxiety)
imagery markers o by structural MRI (i.e. the cortical thickness allowing the quantification of cortical atrophy) o diffusion (i.e. the average diffusivity allowing microstructural integrity to be measured) o T2* relaxometry (i.e. R2* to measure intracerebral iron content) o Resting functional MRI (i.e. connectivity strength of the default mode network)		imagery markers o by structural MRI (i.e. the cortical thickness allowing the quantification of cortical atrophy) o diffusion (i.e. the average diffusivity allowing microstructural integrity to be measured) o T2* relaxometry (i.e. R2* to measure intracerebral iron content) o Resting functional MRI (i.e. connectivity strength of the default mode network)
concentrations of biological markers of peripheral inflammation (TNF alpha and IL6)		concentrations of biological markers of peripheral inflammation (TNF alpha and IL6)
Proteomics: identification of plasma proteins and relative quantification of their abundances		Proteomics: identification of plasma proteins and relative quantification of their abundances

Trial Locations

Locations (4): Centre Hospitalier Charles Perrens
🇫🇷
Bordeaux, France
Centre Hospitalier Universitaire De Bordeaux
🇫🇷
Bordeaux, France
Centre Hospitalier Universitaire De Toulouse
🇫🇷
Toulouse Cedex 9, France
Centre Hospitalier Regional Universitaire De Tours
🇫🇷
Saint-Cyr-Sur-Loire, France
Centre Hospitalier Charles Perrens
🇫🇷Bordeaux, France
Bruno Aouizerate
Site contact
0556561798
bruno.aouizerate@u-bordeaux.fr