Comparison of the Effects of Aripiprazole and Risperidone on the Pattern of Brain Activation in Schizophrenic Patients

Comparison of the Effects of Aripiprazole and Risperidone on the Pattern of Brain Activation in Schizophrenic Patients During Emotional Tasks and With Reference to Controls

After an initial screening visit, including an assessment of psychiatric disorders, patients stabilized on antipsychotic medication (aripiprazole or risperidone) for at least 6 weeks and control subjects will undergo an assessment using functional magnetic resonance imaging (fMRI) of the differences of patterns of brain activation during an emotional task

Study Overview

• Status: Completed
• Conditions: Schizophrenia, Undifferentiated Type
• Intervention / Treatment: Other: Imagery; Genetic: pharmacogenetic sampling

Detailed Description

This study is: interventional, comparative, open label, multi center, without experimental treatment.

Main objective: To evaluate the effect of aripiprazole and risperidone on brain activation during an emotional task of matching patients with schizophrenia, and in reference to control subjects.

Secondary Objective: Comparison of emotional subjective and physiological perception in patients with schizophrenia in relation with their treatment. Comparison of brain activation in patients during the emotional induction task based on symptomatic dimensions, personality traits and performance on cognitive and attentional tests, and for insight capacity . Comparison of transcript level of candidate genes in blood mononuclear cells between the study groups and study the interactions between the observed differences in brain imaging and different levels of transcription of these genes.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13009
    • Sainte-Marguerite Hospital - Psychiatric service -Service du Pr Azorin - 270 boulevard de Sainte Marguerite
  • Marseille cedex 5, France, 13385
    • Hôpital de la Conception - Service du Pr Dassa -147, boulevard Baille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For patients

  1. Men and women, right handed, 18 to 45 years;
  2. Having given their written informed consent;
  3. Presenting a diagnosis of schizophrenia made by DMS IV, hospitalized or followed regularly in a hospital proper, and whose symptoms are stable for at least 6 weeks, at the discretion of the psychiatrist;
  4. Receiving antipsychotic treatment (risperidone or aripiprazole) monotherapy stable (treatment and dose) for at least than 6 weeks;
  5. Showing no contra-indication for fMRI;
  6. Patients whose physical examination is unremarkable clinically significant;
  7. Patients without serious somatic pathology;
  8. Affiliated to a social security system.
  9. For women of childbearing potential, an appropriate contraception is mandatory and an negative pregnancy test

• For controls

  1. Men and women, right handed, aged 18 to 45 years of age, sex and socio-educational level comparable to patients included;
  2. Having given their written informed consent;
  3. Do not present a diagnosis of schizophrenia according to DSM IV set;
  4. Do not present psychiatric history, and free of any psychotropic medication;
  5. Including the physical examination is unremarkable clinically significant;
  6. Having no professional musical practice;
  7. Affiliated with a social security system.

Exclusion Criteria:

• For patients

  1. Patients in menstruation without effective contraception (oral, intramuscular hormonal, intrauterine device, or surgical);
  2. Patients who are pregnant or breastfeeding;
  3. Patients not meeting criteria for schizophrenia according to DSM IV criteria or those with resistant schizophrenia (Kane criteria);
  4. Introducing a somatic disease or serious neurological, particularly Parkinson's disease, epilepsy, tardive dyskinesia and disabling cardiovascular disease, liver or kidney disease;
  5. Presenting a contra-indication to MRI;
  6. Having a history of alcoholism or drug addiction during the past year;
  7. Participating in another clinical trial or are in a period of exclusion from a previous protocol;

  8. Patients likely to have behavioral self aggression from the trial investigators

     During the study:

  1. The investigator considers, for safety reasons, it is in the interest of the patient to be excluded from the study (Hospital readmission due to psychotic symptoms, clinical or psychiatric reasons)
  2. Consentment withdrawal
  3. The patient does not longer correspond to the inclusion criteria or protocol requirements

• For controls

  1. Women of childbearing potential without effective contraception (oral, intramuscular hormonal, intrauterine device, or surgical);
  2. Pregnant or breastfeeding;
  3. Presenting a somatic, psychiatric or neurological disorder;
  4. Presenting a history of alcohol or substance abuse during the past year;
  5. Participating in another clinical trial or are in a period of exclusion from a previous protocol;
  6. Presenting a contra-indication to MRI.

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: aripiprazole; Imagery: A fMRI session is conducted on schizophrenic patients under aripiprazole (medication taken and stabilized for at least six weeks before inclusion, no intervention on the medication is scheduled during the study). Genetic: pharmacogenetic sampling. One sample was collected for each subject.	Other: Imagery; All the subject will be submitted to an functional magnetic resonance imaging (fMRI) examination.; Genetic: pharmacogenetic sampling; A pharmacogenetic sample will be done with an additional consentment.
Active Comparator: risperidone; Imagery: A fMRI session is conducted on schizophrenic patients under rsiperidone (medication taken and stabilized for at least six weeks before inclusion, no intervention on the medication is scheduled during the study). Genetic: pharmacogenetic sampling. One sample was collected for each subject.	Other: Imagery; All the subject will be submitted to an functional magnetic resonance imaging (fMRI) examination.; Genetic: pharmacogenetic sampling; A pharmacogenetic sample will be done with an additional consentment.
Other: control; Imagery: A fMRI session is conducted on healthy volunteers. Genetic: pharmacogenetic sampling. One sample was collected for each subject.	Other: Imagery; All the subject will be submitted to an functional magnetic resonance imaging (fMRI) examination.; Genetic: pharmacogenetic sampling; A pharmacogenetic sample will be done with an additional consentment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of Brain Circuits Involved in a Task of Emotional Congruence (With fMRI)	During the fMRI session, the activation of each brain circuits is measured by a "Bold signal" (an arbitrary measure of contrast: numbers of voxels highlighted/activated in the region of interest). The emotional task is composed by congruent and incongruent images. Three effects were caused by the task: congruence, attention and valence effects. Each of them affect, involve and activate the regions of interests differentially within the differents arms. The region of interests who were mainly observed are: Anterior Cingulate Cortex (ACC), Prefrontal dorso-lateral Cortex (PFdlC) and the Amygdala (A).	3 days after the decision of inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of Emotional Reactivity	3 days after the decision of inclusion
Assessment of Cognitive and Attentional Abilities	3 days after the decision of inclusion
Assessment of Personality Traits	3 days after the decision of inclusion
Investigate the Level of Expression of Candidate Genes	one blood sample

Collaborators and Investigators

• Sponsor: Qualissima
• Investigators: Study Director: Olivier Blin, professor, study coordinator

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: April 21, 2010
• First Submitted That Met QC Criteria: April 22, 2010
• First Posted (Estimate): April 23, 2010

Study Record Updates

• Last Update Posted (Estimate): April 9, 2014
• Last Update Submitted That Met QC Criteria: March 3, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Schizophrenia; Affect; Schizophrenic Disorders; Emotional Blunting
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 2009-017673-38