Research of Anatomo-functional Biomarkers in Schizophrenia

• Conditions: Schizophrenia
• Interventions: Other: fMRI

• Registration Number: NCT03996122
• Lead Sponsor: University Hospital, Caen

Brief Summary

To objectify UR biomarkers, we propose a longitudinal follow-up of resistant patients with schizophrenia, starting before the onset of clozapine and including a multimodal brain imaging assessment (T1 and T2 weighted sequences, DTI, ASL-Perfusion, fMRI- Rest) associated with clinical and biological monitoring. In order to correct the MRI signal of clozapine hemodynamic effects, we will develop a new MRI methodology based on the concomitant collection of physiological parameters (blood pressure, electrocardiogram and respiration).

Detailed Description

The identification of biomarkers of ultra-resistance (UR) to treatment in schizophrenia would allow earlier, better adapted and more effective personalized management of these patients, which would improve their functional prognosis.

An early decrease in functional connectivity (FC) between some rest networks has recently been proposed as an UR biomarker by McNabb et al. Nevertheless, clozapine has, among its side effects, a direct cardiac action that profoundly modifies patient's hemodynamics. However, functional brain imaging techniques are based on BOLD effect which is dependent on these hemodynamic parameters. It is therefore not possible to say whether these differences in FC are inherent to the pathology or whether they are related to clozapine instauration which causes hemodynamic changes that may disturb BOLD signal.

To objectify UR biomarkers, investigators propose a longitudinal follow-up of resistant patients, starting before clozapine instauration and including a multimodal brain imaging assessment (T1 and T2 weighted sequences, DTI, ASL-Perfusion, fMRI- Rest) associated with clinical and biological monitoring. In order to correct the MRI signal of clozapine hemodynamic effects, investigators will develop a new MRI methodology based on the concomitant collection of physiological parameters (blood pressure, electrocardiogram and respiration).

Study Timeline

• Study Start: 2019-04-04
• Study First Submitted: 2019-05-23
• Status Verified: 2019-06
• Study First Submitted QC: 2019-06-21
• Last Update Submitted: 2019-06-21
• Study First Posted: 2019-06-24
• Last Update Posted: 2019-06-24
• Primary Completion: 2021-04-04
• Study Completion: 2021-10-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• schizophrenia or schizoaffective disorder (DSM 5)
• drug resistance
• written patient approval
• social security number in France
• curator or tutor approval if needed

Exclusion Criteria

• pregnancy
• other research participation
• neurological evolution disorder
• no MRI contraindication

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
resistant patients with schizophrenia	fMRI	Age 18 - 60 years No MRI contraindication

Primary Outcome Measures

Name	Time	Method
functional resonance imaging: resting-state	baseline, Month 2 and Month 6	Functional connectivity comparison between baseline, month 2 and month 6

Secondary Outcome Measures

Name	Time	Method
BDNF samples	baseline, Month 2 and Month 6	BDNF concentration comparison between baseline, month 2 and month 6
functional resonance imaging: ASL	baseline, Month 2 and Month 6	Cerebral perfusion comparison between baseline, month 2 and month 6
anatomical resonance imaging: T1	baseline, Month 2 and Month 6	White and gray matter volumetric comparison between baseline, month 2 and month 6
anatomical resonance imaging: DTI	baseline, Month 2 and Month 6	Anatomical connectivity comparison between baseline, month 2 and month 6

Trial Locations

Locations (1)

CHU CAEN Normandie; 🇫🇷 Caen, Normandie, France