Cerebral Neuroinflammation During Major Depressive Episode

NCT03314155 | Unknown

• 2 other identifiers: RC31/16/89182017-001478-40
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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.

Conditions

Depressive Disorder

Keywords

Depressive disorder; Treatment Resistant Depression; [18 F ] DPA- 714; PET; MRI; Inflammation

Outcome Measures

Primary Outcomes (1)

• 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).

  Day 7

Secondary Outcomes (4)

• distribution pattern of neuroinflammation in PET data across all groups

  Day 7

• patients with depressive symptoms and neuroinflammation (i.e. PET data).

  Day 7

• patients with neuroinflammation (i.e. PET analysis) and MRI parameters for functional and structural integrities.

  Day 7

• patients with neuroinflammation (i.e. PET analysis) and biological markers of neuroinflammation (i.e. cytokines).

  Day 7

Study Arms (1)

Cerebral neuroinflammation evaluation

EXPERIMENTAL

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

Diagnostic Test: Cerebral neuroinflammation evaluation

Interventions

Cerebral neuroinflammation evaluation DIAGNOSTIC_TEST

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.

Cerebral neuroinflammation evaluation

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written agreement for participation
• Able to understand instructions and information data
• 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)
• 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)
• Without any neurological or psychiatric previous disorder
• CRPus \< 5mg/L

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Toulouse: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (4)

Hôpital de Psychiatrie

Toulouse, Midi-Pyrénées, 31059, France

RECRUITING

CHU Bordeaux

Bordeaux, Nouvelle-Aquitaine, 33076, France

NOT YET RECRUITING

CHRU Lapeyronie

Montpellier, Occitanie, 34295, France

RECRUITING

Clinique Psychiatrique Universitaire CHRU Tours

Tours, Val-De-Loire, 37540, France

RECRUITING

Related Publications (11)

• Sartorius N. The economic and social burden of depression. J Clin Psychiatry. 2001;62 Suppl 15:8-11.

  PMID: 11444765 BACKGROUND

• Bakish D. New standard of depression treatment: remission and full recovery. J Clin Psychiatry. 2001;62 Suppl 26:5-9.

  PMID: 11775091 BACKGROUND

• Papakostas GI, Petersen T, Mahal Y, Mischoulon D, Nierenberg AA, Fava M. Quality of life assessments in major depressive disorder: a review of the literature. Gen Hosp Psychiatry. 2004 Jan-Feb;26(1):13-7. doi: 10.1016/j.genhosppsych.2003.07.004.

  PMID: 14757297 BACKGROUND

• Schildkraut JJ, Schanberg SM, Breese GR, Kopin IJ. Norepinephrine metabolism and drugs used in the affective disorders: a possible mechanism of action. Am J Psychiatry. 1967 Nov;124(5):600-8. doi: 10.1176/ajp.124.5.600. No abstract available.

  PMID: 4383104 BACKGROUND

• Maes M, Noto C, Brietzke E. Omics-based depression and inflammation research. Braz J Psychiatry. 2015 Jan-Mar;37(1):1-2. doi: 10.1590/1516-4446-2015-3609. No abstract available.

  PMID: 25806550 BACKGROUND

• Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 2007 Feb;64(2):193-200. doi: 10.1001/archpsyc.64.2.193.

  PMID: 17283286 BACKGROUND

• Deschwanden A, Karolewicz B, Feyissa AM, Treyer V, Ametamey SM, Johayem A, Burger C, Auberson YP, Sovago J, Stockmeier CA, Buck A, Hasler G. Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study. Am J Psychiatry. 2011 Jul;168(7):727-34. doi: 10.1176/appi.ajp.2011.09111607. Epub 2011 Apr 15.

  PMID: 21498461 BACKGROUND

• Entsuah AR, Huang H, Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry. 2001 Nov;62(11):869-77. doi: 10.4088/jcp.v62n1106.

  PMID: 11775046 BACKGROUND

• Blumberg HP, Kaufman J, Martin A, Whiteman R, Zhang JH, Gore JC, Charney DS, Krystal JH, Peterson BS. Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry. 2003 Dec;60(12):1201-8. doi: 10.1001/archpsyc.60.12.1201.

  PMID: 14662552 BACKGROUND

• Stone VE, Baron-Cohen S, Calder A, Keane J, Young A. Acquired theory of mind impairments in individuals with bilateral amygdala lesions. Neuropsychologia. 2003;41(2):209-20. doi: 10.1016/s0028-3932(02)00151-3.

  PMID: 12459219 BACKGROUND

• 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.

  PMID: 30087626 DERIVED

MeSH Terms

Conditions

Depressive Disorder; Depressive Disorder, Treatment-Resistant; Inflammation

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Antoine Yrondi, MD PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antoine Yrondi, MD PhD

CONTACT

5 34 55 75 37; yrondi.a@chu-toulouse.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Images' analysis will be done by an INSERM engineer without the knowledge of the group to which the subjects belong.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: October 19, 2017
• Study Start: December 7, 2018
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: March 30, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)