Cerebral Neuroinflammation During Major Depressive Episode

NCT ID: NCT03314155

Last Updated: 2023-03-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-07
• Study Completion Date: 2024-01-31

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.

Conditions

Depressive Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Cerebral neuroinflammation evaluation

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

Group Type: EXPERIMENTAL

Cerebral neuroinflammation evaluation

Intervention Type: 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.

Interventions

Cerebral neuroinflammation evaluation

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• 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

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 (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)

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antoine Yrondi, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

Hôpital de Psychiatrie

Toulouse, Midi-Pyrénées, France

Site Status: RECRUITING

CHU Bordeaux

Bordeaux, Nouvelle-Aquitaine, France

Site Status: NOT_YET_RECRUITING

CHRU Lapeyronie

Montpellier, Occitanie, France

Site Status: RECRUITING

Clinique Psychiatrique Universitaire CHRU Tours

Tours, Val-De-Loire, France

Site Status: RECRUITING

Countries

France

Central Contacts

Antoine Yrondi, MD PhD

Role: CONTACT

yrondi.a@chu-toulouse.fr

5 34 55 75 37 ext. 33

Facility Contacts

Antoine Yrondi, PhD

Role: primary

yrondi.a@chu-toulouse.fr

5 34 55 75 37 ext. 33

Bruno Aouizerate, PhD

Role: primary

bruno.aouizerate@u-bordeaux.fr

5 56 56 17 98 ext. 33

Fanny Molière, PhD

Role: primary

moliere@chu-montpellier.fr

4 67 33 67 33 ext. 33

Wissam El-Hage, PhD

Role: primary

wissam.elhage@univ-tours.fr

2 47 47 80 43 ext. 33

References

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

Reference Type: BACKGROUND

PMID: 11444765 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 11775091 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14757297 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 4383104 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25806550 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17283286 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21498461 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11775046 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14662552 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12459219 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30087626 (View on PubMed)

Other Identifiers

2017-001478-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RC31/16/8918

Identifier Type: -

Identifier Source: org_study_id