Research of Anatomo-functional Biomarkers in Schizophrenia

Schizophrenia Clinical Trial

— CLOZAREST  

Official title:

Research of Anatomo-functional Biomarkers in Schizophrenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03996122
• Other study ID #: 2018-A03281-54
• Status: Recruiting
• Start date: April 4, 2019
• Est. completion date: October 4, 2021

Study information

• Verified date: June 2019
• Source: University Hospital, Caen
• Contact: Anaïs Vandevelde, MD
• Phone: 0231064422
• Email: vandevelde-a[@]chu-caen.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: October 4, 2021
• Est. primary completion date: April 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Other:
• fMRI
3 fMRI (TO, Month 2 and Month 6) 3 BDNF samples (TO, Month 2 and Month 6)

Locations

Country	Name	City	State
France	CHU CAEN Normandie	Caen	Normandie

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Caen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	functional resonance imaging: resting-state	Functional connectivity comparison between baseline, month 2 and month 6	baseline, Month 2 and Month 6
Secondary	BDNF samples	BDNF concentration comparison between baseline, month 2 and month 6	baseline, Month 2 and Month 6
Secondary	functional resonance imaging: ASL	Cerebral perfusion comparison between baseline, month 2 and month 6	baseline, Month 2 and Month 6
Secondary	anatomical resonance imaging: DTI	Anatomical connectivity comparison between baseline, month 2 and month 6	baseline, Month 2 and Month 6
Secondary	anatomical resonance imaging: T1	White and gray matter volumetric comparison between baseline, month 2 and month 6	baseline, Month 2 and Month 6

External Links

•   Abnormalities of fronto-subcortical pathways in schizophrenia and the differential impacts of antipsychotic treatment: a DTI-based tractography study
•   Functional network dysconnectivity as a biomarker of treatment resistance in schizophrenia