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Status unknownNCT03314155InflaDepUpdated Mar 30, 2023

Cerebral Neuroinflammation During Major Depressive Episode

An interventional study of Cerebral neuroinflammation evaluation in Depressive Disorder, sponsored by University Hospital, Toulouse. Status unknown at 4 sites in France. Open to participants aged 25 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-03-30.

Sponsored by University Hospital, Toulouse · Not applicable, Interventional, and Diagnostic

The sponsor has not verified this record recently (last verified Mar 2023), so the status shown — last known as Recruiting — may be out of date.
Phase
Not applicable
Study type
Interventional
Enrollment
60
Allocation
Not applicable
Ages
25 Years to 55 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Depressive Disorder

Keywords

  • Depressive disorder
  • Treatment Resistant Depression
  • [18 F ] DPA- 714
  • PET
  • MRI
  • Inflammation
03

Who can participate

Ages eligible
25 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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)
04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
60 participants (estimated)

Study arms

  • Experimental
    Cerebral neuroinflammation evaluation

    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

  • Diagnostic testCerebral 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.

05

What researchers measure

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).

    Time frame: Day 7

Secondary outcomes

  1. distribution pattern of neuroinflammation in PET data across all groups

    Across all groups (i.e. experimental group, pathological control group and control group).

    Time frame: Day 7

  2. 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).

    Time frame: Day 7

  3. 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).

    Time frame: Day 7

  4. 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).

    Time frame: Day 7

06

Study locations

3 of 4 sites recruiting
  • Hôpital de Psychiatrie
    Toulouse, Midi-Pyrénées 31059, France
    • Antoine Yrondi, PhD · Contact · yrondi.a@chu-toulouse.fr · 5 34 55 75 37
    • Antoine Yrondi, MD PhD · Principal investigator
    • Christophe Arbus, MD · Sub investigator
    • Marie Sporer, PhD · Sub investigator
    • Laurent Schmitt, MD · Sub investigator
    • Claire Thalamas, MD · Sub investigator
    • Fabienne Calvas, MD · Sub investigator
    • Monique Galitski, MD · Sub investigator
    • Pierre Payoux, MD · Sub investigator
    Recruiting
  • CHU Bordeaux
    Bordeaux, Nouvelle Aquitaine 33076, France
    • Bruno Aouizerate, PhD · Contact · bruno.aouizerate@u-bordeaux.fr · 5 56 56 17 98
    • Bruno Aouizerate, PhD · Principal investigator
    • Philippe Fernandez, PhD · Sub investigator
    • Marie Meyer, PhD · Sub investigator
    • Vincent Dousset, Pr · Sub investigator
    Not yet recruiting
  • CHRU Lapeyronie
    Montpellier, Occitanie 34295, France
    • Fanny Molière, PhD · Contact · moliere@chu-montpellier.fr · 4 67 33 67 33
    • Fanny Molière, PhD · Principal investigator
    • Sébastien Guillaume, PhD · Sub investigator
    • Philippe Courtet, PhD · Sub investigator
    • Florence Galtier, PhD · Sub investigator
    • Denis Mariano-Goulard, Pr · Sub investigator
    • Nicolas Menjot De Champfleur, PhD · Sub investigator
    Recruiting
  • Clinique Psychiatrique Universitaire CHRU Tours
    Tours, Val-De-Loire 37540, France
    • Wissam El-Hage, PhD · Contact · wissam.elhage@univ-tours.fr · 2 47 47 80 43
    • Wissam El-Hage, PhD · Principal investigator
    • Vincent Camus, Pr · Sub investigator
    • Valérie Gissot, PhD · Sub investigator
    • Thomas Desmidt, PhD · Sub investigator
    • Mathieu Lemaire, PhD · Sub investigator
    • Maria-Joao Santiago-Ribeiro, PhD · Sub investigator
    • Jean-Philippe Cottier, PhD · Sub investigator
    Recruiting
07

References and documents

Publications

  • Sartorius N. The economic and social burden of depression. J Clin Psychiatry. 2001;62 Suppl 15:8-11. PubMed 11444765 ↗
  • Bakish D. New standard of depression treatment: remission and full recovery. J Clin Psychiatry. 2001;62 Suppl 26:5-9. PubMed 11775091 ↗
  • 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. PubMed 14757297 ↗
  • 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. PubMed 4383104 ↗
  • 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. PubMed 25806550 ↗
  • 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. PubMed 17283286 ↗
  • 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. PubMed 21498461 ↗
  • 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. PubMed 11775046 ↗
  • 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. PubMed 14662552 ↗
  • 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. PubMed 12459219 ↗
  • 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. PubMed 30087626 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03314155
Lead sponsor
University Hospital, Toulouse
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
Responsible party
Sponsor
First posted
Oct 19, 2017
Start date
Dec 7, 2018
Primary completion
Jan 2024 (estimated)
Completion
Jan 2024 (estimated)
Last update
Mar 30, 2023

Study contacts

Antoine Yrondi, MD PhD
Contact
yrondi.a@chu-toulouse.fr
5 34 55 75 37 ext. 33
Antoine Yrondi, MD PhD
principal investigator · University Hospital, Toulouse

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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