Assessment of microglial activation in patients with schizophrenia stratified for C4 complement by PET using [18F]DPA-714

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut National De La Sante Et De La Recherche Medicale

Participant type

Healthy volunteers, Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03], Diseases [C] - Pathological Conditions, Signs and Symptoms [C23], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

Trial duration

17 Nov 2025 → ongoing

Decision date (initial)

2023-05-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To assess the correlation between cortical neuro-inflammation quantified by Positrons Emission Tomography (PET) using [18F]DPA-714, and genetic determinants of C4 expression in patients with schizophrenia and healthy volunteers.

Secondary objectives 3

1. To assess the correlation between cortical and subcortical markers in Magnetic Resonance Imagery (MRI), PET using [18F]DPA-714 neuro-inflammation markers and genetic determinants of C4 expression in patients with schizophrenia and healthy volunteers.
2. To assess the correlation between cortical neuro-inflammation and peripheric inflammation biomarkers (cytokine levels, C-reactive protein (CRP), lipid anomalies…)
3. To assess the correlation between cortical neuro-inflammation and clinical determinants of inflammation.

Conditions and MedDRA coding

pathology studied is schizophrenia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or Female, aged from 18 to 55, patients with schizophrenia diagnostic according to DSM-5 and presenting HLA 8.1 AH haplotype (8.1 AH+) or presenting no HLA 8.1 AH haplotype ( (8.1 AH-)
2. Male or Female healthy controls aged from 18 to 55 matched regarding age, sex, HLA/C4 according to patients (8.1 AH+ or 8.1 AH-).
3. Having Efficient Contraception for women of reproductive age ( contraception will be considered effective from the moment the patient declares the use of an oral contraceptive, the presence of an IUD other than copper ones, a diaphragm or a contraceptive implant, or the completion of a tubal ligation or sterilization by Essure process)
4. Be able to understand research objectives and procedures
5. Be affiliated with or be a beneficiary of a social security scheme
6. Genetic criterion: TSPO genotype allowing tracer fixation (90% of subjects)
7. Have signed a free and informed consent

Exclusion criteria 11

1. Progressive chronic inflammatory disease (rheumatic, digestive, autoimmune)
2. Known hypersensitivity to radiopharmaceutical ([18F]DPA-714 or one of the excipients)
3. History of severe renal or liver failure
4. Contraindication to MRI : pacemaker or neurosensory pacemaker or implantable defibrillator; clip on an aneurysm or clip on a vascular malformation of the brain; ferromagnetic intraocular or cerebral foreign body; prosthesis or ferro-metallic objects or fragments mobilizable magnetic; cochlear implants; peripheral stimulator; ventriculoperitoneal neurosurgical bypass valves; permanent eye or lip makeup. Automatic injection device type insulin pump, blood glucose sensor
5. Claustrophobia
6. Current pregnancy, breastfeeding
7. Person refusing to be informed of a significant health finding discovered in the research
8. Participation in research or management of a pathology with ionizing radiation exposure as part of a nuclear medicine examination (PET, SPECT, NM) in the year prior to or during the exclusion period of another research
9. Person deprived of liberty by administrative or judicial decision
10. Adult subject to legal protection (guardianship of a tutor, or safeguard of justice)
11. For healthy volunteers only : Pathology or history of Axis 1 psychiatric pathology investigated by the validated French version of the MINI (Mini International Neuropsychiatric Interview) questionnaire

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main evaluation criterion is the level of microglial activation measured in PET with [ 18F]-DPA714 in the brain, which will be compared between groups according to the genotype of C4 weighted by the ancestral haplotype that carries it

Secondary endpoints 3

1. - Regional cortical thicknesses as determined on anatomical MRI
2. Parameters of subcortical brain connectivity (variables derived from diffusion MRI such as fractional anisotropy and resting functional MRI such as functional connectivity) which will be compared between groups according to the C4 genotype.
3. Lipid abnormalities (cholesterol, serum triglycerides), blood glucose, peripheral markers of inflammation (CRP, cytokines) and clinical parameters (abdominal tension, abdominal girth) will also be correlated to the level of microglial activation measured in PET

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut National De La Sante Et De La Recherche Medicale

Sponsor organisation

Institut National De La Sante Et De La Recherche Medicale

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Institut National De La Sante Et De La Recherche Medicale

Contact name

Corentin LE-MARGUERESSE

Public contact point

Organisation

Institut National De La Sante Et De La Recherche Medicale

Contact name

Marion LEBOYER

Third parties 3

Locations

1 EU/EEA country · 2 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 29 files

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

Application history

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