Research of Anatomo-functional Biomarkers in Schizophrenia (CLOZAREST)

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).

Study Overview

• Status: Unknown
• Conditions: Schizophrenia
• Intervention / Treatment: Other: fMRI

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 Type: Observational
• Enrollment (Anticipated): 15

Contacts and Locations

• Study Contact: Name: Anaïs Vandevelde, MD; Phone Number: +33 0231064422; Email: vandevelde-a@chu-caen.fr
• Study Contact Backup: Name: Olivier Etard, MD; Phone Number: +33 0231470200; Email: etard-o@chu-caen.fr

Study Locations

• France
  • Normandie
    • Caen, Normandie, France, 14000
      • Recruiting
      • CHU Caen Normandie
      • Contact: Anaïs Vandevelde, MD; Phone Number: +33 231065062; Email: vandevelde-a@chu-caen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

resistant schizophrenia or schizoaffective disorder patients

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
resistant patients with schizophrenia; Age 18 - 60 years No MRI contraindication	Other: fMRI; 3 fMRI (TO, Month 2 and Month 6) 3 BDNF samples (TO, Month 2 and Month 6); Other Names: BDNF samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
functional resonance imaging: resting-state	Functional connectivity comparison between baseline, month 2 and month 6	baseline, Month 2 and Month 6

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital, Caen
• Investigators: Principal Investigator: Anaïs Vandevelde, MD, CHU of Caen, Esquirol

Publications and helpful links

Helpful 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

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 4, 2019
• Primary Completion (ANTICIPATED): April 4, 2021
• Study Completion (ANTICIPATED): October 4, 2021

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: June 21, 2019
• First Posted (ACTUAL): June 24, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 24, 2019
• Last Update Submitted That Met QC Criteria: June 21, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: biomarker; fMRI; clozapine; schizo-affective disorder; utra-resistance
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 2018-A03281-54

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No