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Cerebral Neuroinflammation During Major Depressive Episode (InflaDep)

Primary Purpose

Depressive Disorder

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Cerebral neuroinflammation evaluation
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Depressive Disorder focused on measuring Depressive disorder, Treatment Resistant Depression, [18 F ] DPA- 714, PET, MRI, Inflammation

Eligibility Criteria

25 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

  • 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)

Sites / Locations

  • Hôpital de PsychiatrieRecruiting
  • CHU Bordeaux
  • CHRU LapeyronieRecruiting
  • Clinique Psychiatrique Universitaire CHRU ToursRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cerebral neuroinflammation evaluation

Arm Description

The density of TSPO (which is an inflammation maker) is evaluated by the tracer's brain distribution volume ([18F] DPA-714).

Outcomes

Primary Outcome Measures

distribution pattern of neuroinflammation in Positron Emission Tomography (PET) data
Assessed 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).

Secondary Outcome Measures

distribution pattern of neuroinflammation in PET data across all groups
Across all groups (i.e. experimental group, pathological control group and control group).
patients with depressive symptoms and neuroinflammation (i.e. PET data).
Depressive symptoms are assessed by the Montgomery and Asberg Depression Scale (MADRS) and the Columbia-Suicide severity rating scale (CSSRS). Correlation across all groups (experimental group, pathological control group and control group).
patients with neuroinflammation (i.e. PET analysis) and MRI parameters for functional and structural integrities.
Correlation across all groups (experimental group, pathological control group and control group).
patients with neuroinflammation (i.e. PET analysis) and biological markers of neuroinflammation (i.e. cytokines).
Correlation across all groups (experimental group, pathological control group and control group).

Full Information

First Posted
August 21, 2017
Last Updated
March 29, 2023
Sponsor
University Hospital, Toulouse
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
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1. Study Identification

Unique Protocol Identification Number
NCT03314155
Brief Title
Cerebral Neuroinflammation During Major Depressive Episode
Acronym
InflaDep
Official Title
Cerebral Neuroinflammation During Major Depressive Episode: Multicentric Comparative Study.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 7, 2018 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder
Keywords
Depressive disorder, Treatment Resistant Depression, [18 F ] DPA- 714, PET, MRI, Inflammation

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
Images' analysis will be done by an INSERM engineer without the knowledge of the group to which the subjects belong.
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cerebral neuroinflammation evaluation
Arm Type
Experimental
Arm Description
The density of TSPO (which is an inflammation maker) is evaluated by the tracer's brain distribution volume ([18F] DPA-714).
Intervention Type
Diagnostic Test
Intervention Name(s)
Cerebral neuroinflammation evaluation
Intervention Description
Pet scan following an injection of the radiotracer ([18F]DPA-714), to evaluate the neuroinflammation. MRI to evaluate functional and structural integrities. Blood test to analyze various inflammation marker (IL-6, Tumor Necrosis Factor (TNF) alpha, CRPus, and TSPO). And psychological scales to assess the depressive symptoms.
Primary Outcome Measure Information:
Title
distribution pattern of neuroinflammation in Positron Emission Tomography (PET) data
Description
Assessed 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).
Time Frame
Day 7
Secondary Outcome Measure Information:
Title
distribution pattern of neuroinflammation in PET data across all groups
Description
Across all groups (i.e. experimental group, pathological control group and control group).
Time Frame
Day 7
Title
patients with depressive symptoms and neuroinflammation (i.e. PET data).
Description
Depressive symptoms are assessed by the Montgomery and Asberg Depression Scale (MADRS) and the Columbia-Suicide severity rating scale (CSSRS). Correlation across all groups (experimental group, pathological control group and control group).
Time Frame
Day 7
Title
patients with neuroinflammation (i.e. PET analysis) and MRI parameters for functional and structural integrities.
Description
Correlation across all groups (experimental group, pathological control group and control group).
Time Frame
Day 7
Title
patients with neuroinflammation (i.e. PET analysis) and biological markers of neuroinflammation (i.e. cytokines).
Description
Correlation across all groups (experimental group, pathological control group and control group).
Time Frame
Day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antoine Yrondi, MD PhD
Phone
5 34 55 75 37
Ext
33
Email
yrondi.a@chu-toulouse.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antoine Yrondi, MD PhD
Organizational Affiliation
University Hospital, Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital de Psychiatrie
City
Toulouse
State/Province
Midi-Pyrénées
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine Yrondi, PhD
Phone
5 34 55 75 37
Ext
33
Email
yrondi.a@chu-toulouse.fr
First Name & Middle Initial & Last Name & Degree
Antoine Yrondi, MD PhD
First Name & Middle Initial & Last Name & Degree
Christophe Arbus, MD
First Name & Middle Initial & Last Name & Degree
Marie Sporer, PhD
First Name & Middle Initial & Last Name & Degree
Laurent Schmitt, MD
First Name & Middle Initial & Last Name & Degree
Claire Thalamas, MD
First Name & Middle Initial & Last Name & Degree
Fabienne Calvas, MD
First Name & Middle Initial & Last Name & Degree
Monique Galitski, MD
First Name & Middle Initial & Last Name & Degree
Pierre Payoux, MD
Facility Name
CHU Bordeaux
City
Bordeaux
State/Province
Nouvelle Aquitaine
ZIP/Postal Code
33076
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bruno Aouizerate, PhD
Phone
5 56 56 17 98
Ext
33
Email
bruno.aouizerate@u-bordeaux.fr
First Name & Middle Initial & Last Name & Degree
Bruno Aouizerate, PhD
First Name & Middle Initial & Last Name & Degree
Philippe Fernandez, PhD
First Name & Middle Initial & Last Name & Degree
Marie Meyer, PhD
First Name & Middle Initial & Last Name & Degree
Vincent Dousset, Pr
Facility Name
CHRU Lapeyronie
City
Montpellier
State/Province
Occitanie
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fanny Molière, PhD
Phone
4 67 33 67 33
Ext
33
Email
moliere@chu-montpellier.fr
First Name & Middle Initial & Last Name & Degree
Fanny Molière, PhD
First Name & Middle Initial & Last Name & Degree
Sébastien Guillaume, PhD
First Name & Middle Initial & Last Name & Degree
Philippe Courtet, PhD
First Name & Middle Initial & Last Name & Degree
Florence Galtier, PhD
First Name & Middle Initial & Last Name & Degree
Denis Mariano-Goulard, Pr
First Name & Middle Initial & Last Name & Degree
Nicolas Menjot De Champfleur, PhD
Facility Name
Clinique Psychiatrique Universitaire CHRU Tours
City
Tours
State/Province
Val-De-Loire
ZIP/Postal Code
37540
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wissam El-Hage, PhD
Phone
2 47 47 80 43
Ext
33
Email
wissam.elhage@univ-tours.fr
First Name & Middle Initial & Last Name & Degree
Wissam El-Hage, PhD
First Name & Middle Initial & Last Name & Degree
Vincent Camus, Pr
First Name & Middle Initial & Last Name & Degree
Valérie Gissot, PhD
First Name & Middle Initial & Last Name & Degree
Thomas Desmidt, PhD
First Name & Middle Initial & Last Name & Degree
Mathieu Lemaire, PhD
First Name & Middle Initial & Last Name & Degree
Maria-Joao Santiago-Ribeiro, PhD
First Name & Middle Initial & Last Name & Degree
Jean-Philippe Cottier, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
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derived

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Cerebral Neuroinflammation During Major Depressive Episode

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