Cerebral neuroinflammation during major depressive episode: multicentric comparative study (InflaDep)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients, Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03], Psychiatry and Psychology [F] - Psychological Phenomena [F02]

Trial duration

7 Dec 2018 → 18 Dec 2025

Decision date (initial)

2024-12-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518405-18-00

EudraCT number

2017-001478-40

ClinicalTrials.gov

NCT03314155

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

The primary outcome is to compare TEP data (i.e. distribution pattern of neuroinflammation) 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 objectives 6

1. • Compare TEP data (i.e. distribution pattern of neuroinflammation) accross groups (experimental group, pathological control group and control group)
2. • Correlate depressive symptoms (assessed by Montgomery and Asberg Depression Scale – MADRS and Columbia-Suicide severity rating scale - CSSRS) with neuroinflammation (evaluated in TEP scan) across groups (experimental group, pathological control group and control group)
3. • Correlate neuroinflammation (i.e. TEP analysis) and MRI parameters for functional and structural integrities across groups
4. • Correlate neuroinflammation (i.e. TEP analysis) and biological markers of neuroinflammation (i.e. cytokines) across groups
5. Compare the proteomic markers between the three groups of subjects
6. Measure the correlation between the volume of distribution of TSPO assessed by PET, MRI markers, biological markers of peripheral inflammation and proteomic markers in the three groups of subjects.

Conditions and MedDRA coding

Depressive disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Male or female / age between 18 and 60 years
2. Written agreement for participation
3. Able to understand instructions and information data
4. for the experimental group: Responding to MDD criteria (DSM-5)
5. for the experimental group: MADRS score> 20
6. for the experimental group: Antidepressant medication considered ineffective and before the introduction of a new treatment according to the recommendations (unchanged dosage for at least 2 week and plasma levels above the lower end of the therapeutic range done after one week more with unchanged dosage).
7. for the pathological control group : Having met MDD criteria (DSM-5)
8. for the pathological control group : In remission for 8 weeks according to the DSM-5
9. for the pathological control group : MADRS score <10
10. for the pathological control group : Treated with antidepressants (unchanged dosage for at least week)
11. for the control group : Without any neurological or psychiatric previous disorder
12. for the control group : CRPus < 5mg/L

Exclusion criteria 18

1. Patients without public insurance regime.
2. Patients with chronic inflammatory pathology.
3. Patients treated with anti-inflammatory and/or immunosuppressive, and/or antipsychotics, and/or benzodiazepine
4. Diabetics
5. History of documented head trauma
6. for control group: No significant psychiatric or somatic history.
7. for control group: No psychotropic treatment
8. for control group: Suicidal risk (C-SSRS)
9. for control group: Anxiety Disorders (MINI)
10. Specific contraindication to the use of MRI (metallic material) or PET (specific allergy related to the ligand).
11. Pregnant and breastfeeding women
12. Persons deprived of liberty by judicial or administrative decision
13. People hospitalized without consent, or subject to legal protection
14. Persons unable to consent
15. Patients with a neurodegenerative disease, bipolar disease, chronic psychotic disorder, addictive disorder, Obsessive Compulsive Disorder, Post-Traumatic Stress disorder, known system pathology
16. Patients with a history of stroke
17. Patients with an acute infectious disease
18. Persons with a phenotype of low affinity to the TSPO tracer

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. TSPO density assessed by the cerebral distribution volume of the tracer [18F]DPA-714 in the experimental group versus the control group.

Secondary endpoints 5

1. the density of the TSPO evaluated by the cerebral distribution volume of the tracer [18F]DPA-714 in the 3 groups (experimental, control and pathological control).
2. psychometric scales making it possible to assess the clinical state of subjects: o Depression scale (MADRS) o Anhedonia Scale (SHAPS) o Psychomotor slowing scale (Widlocher scale) o Suicide Risk Rating Scale (CSSRS) o BAS Anxiety Rating Scale (Brief Scale for Anxiety)
3. imagery markers o by structural MRI (i.e. the cortical thickness allowing the quantification of cortical atrophy) o diffusion (i.e. the average diffusivity allowing microstructural integrity to be measured) o T2* relaxometry (i.e. R2* to measure intracerebral iron content) o Resting functional MRI (i.e. connectivity strength of the default mode network)
4. concentrations of biological markers of peripheral inflammation (TNF alpha and IL6)
5. Proteomics: identification of plasma proteins and relative quantification of their abundances

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Dr Antoine YRONDI

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Amandine PAUZE

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications