Cerebral Neuroinflammation During Major Depressive Episode

Depressive Disorder Clinical Trial

— InflaDep  

Official title:

Cerebral Neuroinflammation During Major Depressive Episode: Multicentric Comparative Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03314155
• Other study ID #: RC31/16/8918
• Secondary ID: 2017-001478-40
• Status: Recruiting
• Phase: N/A
• Start date: December 7, 2018
• Est. completion date: January 2024

Study information

• Verified date: March 2023
• Source: University Hospital, Toulouse
• Contact: Antoine Yrondi, MD PhD
• Phone: 5 34 55 75 37
• Email: yrondi.a[@]chu-toulouse.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 55 Years

Eligibility

• 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)

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

Diagnostic Test:
• 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.

Locations

Country	Name	City	State
France	CHU Bordeaux	Bordeaux	Nouvelle Aquitaine
France	CHRU Lapeyronie	Montpellier	Occitanie
France	Hôpital de Psychiatrie	Toulouse	Midi-Pyrénées
France	Clinique Psychiatrique Universitaire CHRU Tours	Tours	Val-De-Loire

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Toulouse	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (10)

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	distribution pattern of neuroinflammation in PET data across all groups	Across all groups (i.e. experimental group, pathological control group and control group).	Day 7
Secondary	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).	Day 7
Secondary	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).	Day 7
Secondary	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).	Day 7