"Manual Dexterity and Oculomotor Control in Schizophrenia"

Schizophrenia Clinical Trial

— MADOCS  

Official title:

"MADOCS: Manual Dexterity and Oculomotor Control as Vulnerability Markers in Schizophrenia"

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02826629
• Other study ID #: D16-P01
• Status: Recruiting
• Phase: N/A
• First received: May 20, 2016
• Last updated: October 18, 2017
• Start date: July 26, 2016
• Est. completion date: January 2019

Study information

• Verified date: October 2017
• Source: Centre Hospitalier St Anne
• Contact: Isabelle Amado, Dr
• Phone: 00 33 1 45 65 81 79
• Email: i.amado[@]ch-sainte-anne.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators recently showed that visuomotor integration was significantly altered in schizophrenic patients during: (i) a grip force task (Teremetz et al., 2014), and (ii) a saccadic paradigm (oculomotor task)(Amado et al., 2008). Given this findings, the investigators propose a combined study of oculomotor and grip force control to better characterize the sensorimotor integration deficit. This approach may allow for identification of behavioural biomarkers of vulnerability to develop schizophrenia.

Description:

1 - Scientific background and rational Use of sensory cues is essential for execution and correction of voluntary movements. The motor areas and their regulation is of special interest in patients with schizophrenia as there is clear evidence of motor abnormalities independent of the effects of antipsychotic medication, even before the onset of the disorder. Sensorimotor abnormalities have been proposed as a valid endophenotype in schizophrenia. Our global objective is to study and provide vulnerability markers for schizophrenia.

1. Control of manual dexterity will be assessed by a force sensor (Power Grip Manipulandum, PGM)

2. Oculomotor movements during behavioral task will be recorded using a video-oculography device

3. The involvement of cortical inhibition in this volitional inhibition task will be studied by neuronavigation guided TMS coupled to EMG recording

2 - Description of the project methodology There is strong evidence for schizophrenia being a neuro-developmental disorder (Rapoport et al., 2005). It has been shown, for many years, that patients with schizophrenia exhibit abnormal patterns of sensorimotor integration (Manschreck et al., 1982), which is the capacity to integrate different sensory stimuli into appropriate motor actions. It is clinically relevant, in terms of early diagnosis and prevention, whether deficient sensorimotor integration is present in the prodromal phase of schizophrenia, and whether this constitutes a vulnerability marker for the disease.

Our global objective is to study the interactions and related substratum of oculomotor movements during force control task.

The secondary objectives:

(i) To show that increased motor noise is indeed present in schizophrenia. (ii) To show by TMS that cortical excitability in the primary motor cortex (M1) is task-modulated and decreased in schizophrenia.

(iii) Assess the role of deficient cortical inhibition in these behavioral deficits To this end, three different groups of subjects will be studied: schizophrenic patients, non-affected siblings, ultra high risk patients, non-treated schizophrenic patients and healthy control subjects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: January 2019
• Est. primary completion date: September 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• All groups:

1. 18>yrs<50

2. Medical visit completed

3. Visual acuity (9/10 for each eye or corrected)

4. Provided written informed consent

• Group of patient suffering from schizophrenia:

4. DSM-IV-TR diagnostic criteria for schizophrenia 5. Treatment: stable atypical anti-psychotic medication for >3 months prior to the study

• Group of UHR patient:

6. 18>yrs<30 7. Fulfill at risk criteria of CAARMS diagnostic tool

Exclusion Criteria:

• All groups:

1. IQ<70,

2. Contraindications for TMS protocol: no previous history of neurosurgery or seizures or 1st degree relative with history of seizures, heart disease, drug abuse or addiction in the last 12 months, medications that lower seizure threshold including clozapine, bupropion, méthadone or theophylline.

3. Metallic implant in head (except dental fillings)

4. Pacemaker, or other electronic implanted devices

5. Central neurological disease: parkinsonism, x

6. Severe heart attack

7. Instable clinical state (e.g. stroke)

8. Previous history of drug abuse lasting more than 5 years or during the last year

9. Life event with a moderate to severe impact

10. Caffeine intake in the last two hours preceding visuomotor assessment

• Groups of Siblings and Healthy controls:

11. No previous history of psychiatric disease, psychotic spectrum disorder (according to DIGS 3.0)

12. No previous history of antipsychotic medication (entire life)

• Groups of UHR patient:

13. Chlorpromazine dose >100mg over more than 12 weeks

14. No previous history of autism spectrum disorder, bipolar disorder or diagnozed schizophrenia (according to DSM-IV-TR criteria), isolated anxiety disorders (e.g. social phobia, agoraphobia)

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Device:
• Manual dexterity
Control of manual dexterity will be assessed by a force sensor (Power Grip Manipulandum, PGM)
• Oculomotor movements
Oculomotor movements during behavioral task will be recorded using a video-oculography device
• TMS coupled to EMG recording
The involvement of cortical inhibition in this volitional inhibition task will be studied by neuronavigation guided TMS coupled to EMG recording

Other:
• Psychopathological evaluations

• Neuropsychological evaluations

Locations

Country	Name	City	State
France	Centre de Recherche Clinique (CRC) - CHSA	Paris
France	Service Hospitalo-Universitaire (SHU) - CHSA	Paris

Sponsors (3)

Lead Sponsor	Collaborator
Centre Hospitalier St Anne	Institut National de la Santé Et de la Recherche Médicale, France, University of Paris 5 - Rene Descartes

Country where clinical trial is conducted

France, 

References & Publications (2)

Amado I, Landgraf S, Bourdel MC, Leonardi S, Krebs MO. Predictive saccades are impaired in biological nonpsychotic siblings of schizophrenia patients. J Psychiatry Neurosci. 2008 Jan;33(1):17-22. — View Citation

Teremetz M, Amado I, Bendjemaa N, Krebs MO, Lindberg PG, Maier MA. Deficient grip force control in schizophrenia: behavioral and modeling evidence for altered motor inhibition and motor noise. PLoS One. 2014 Nov 4;9(11):e111853. doi: 10.1371/journal.pone.0111853. eCollection 2014. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Behavioural assessment	Index reflecting motor performance during visuomotor task (including force and oculomotor control)	BASELINE
Secondary	Clinical scale : PANSS	Positive and Negative Syndrome Scale: Assess positive and negative symptoms	BASELINE
Secondary	Clinical scale : DIGS III	Diagnostic Interview for Genetic Studies 3.0: Overview of clinical state	BASELINE
Secondary	Clinical scale : BPRS	Brief Psychiatric Rating Scale: Assess schizophrenic symptoms	BASELINE
Secondary	Clinical scale : SAS	Simpson Angus Extra-Pyramidal Scale: Asses extra-pyramidal signs	BASELINE
Secondary	Clinical scale : AIMS	Abnormal Involuntary Movements Scale: Assess abnormal involuntary movements	BASELINE
Secondary	Clinical scale : TAP	Test battery for Attentional Performance: Assess attentional capacity (e.g. working memory)	BASELINE
Secondary	Clinical scale : Stroop	Stroop color naming test: Assess selective attention or inhibition.	BASELINE
Secondary	Clinical scale : WASI	Wechsler Abbreviated Scale of Intelligence: Assess intelligence quotient	BASELINE
Secondary	Tracking performance (motor task): RMS Error	RMS Error (Root Mean Square)	BASELINE
Secondary	Tracking performance (motor task): Coefficient of variability	Coefficient of variability	BASELINE
Secondary	Tracking performance (motor task): Timing	Timing/inhibition	BASELINE
Secondary	Ocolomotor performance (eye tracker) : Saccade	Saccade error (back up/ catch up saccades) during smooth pursuit and fixation	BASELINE
Secondary	Ocolomotor performance (eye tracker): Gain	Gain (target velocity/gaze velocity), Reaction time	BASELINE
Secondary	Ocolomotor performance (eye tracker): Amplitude of eye movements	Amplitude (°) and velocity (°/s) of saccadic movements	BASELINE
Secondary	Motor noise	Variability of EMG response during visuomotor task	BASELINE
Secondary	Cortical excitability (MEP; TMS)	Motor evoked potential (MEP) during visuomotor task (single pulse TMS)	BASELINE
Secondary	Cortical inhibition (SICI; TMS)	Cortical inhibition measured during visuomotor task (paired-pulse TMS; MEP)	BASELINE