Clinical trial NCT02826629: "Manual Dexterity and Oculomotor Control in Schizophrenia"
Official title: "MADOCS: Manual Dexterity and Oculomotor Control as Vulnerability Markers in Schizophrenia"
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Schizophrenia
Keywords: Sensorimotor Integration
Schizophrenia
TMS
Oculomotor
Motor Control
Lead sponsor: Centre Hospitalier St Anne
Sponsor class: OTHER
Collaborators: name: University of Paris 5 - Rene Descartes
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2016-07-11
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Behavioural assessment
timeFrame: BASELINE
Secondary outcomes:
measure: Clinical scale : PANSS
timeFrame: BASELINE
measure: Clinical scale : DIGS III
timeFrame: BASELINE
measure: Clinical scale : BPRS
timeFrame: BASELINE
measure: Clinical scale : SAS
timeFrame: BASELINE
measure: Clinical scale : AIMS
timeFrame: BASELINE
measure: Clinical scale : TAP
timeFrame: BASELINE
measure: Clinical scale : Stroop
timeFrame: BASELINE
measure: Clinical scale : WASI
timeFrame: BASELINE
measure: Tracking performance (motor task): RMS Error
timeFrame: BASELINE
measure: Tracking performance (motor task): Coefficient of variability
timeFrame: BASELINE
measure: Tracking performance (motor task): Timing
timeFrame: BASELINE
measure: Ocolomotor performance (eye tracker) : Saccade
timeFrame: BASELINE
measure: Ocolomotor performance (eye tracker): Gain
timeFrame: BASELINE
measure: Ocolomotor performance (eye tracker): Amplitude of eye movements
timeFrame: BASELINE
measure: Motor noise
timeFrame: BASELINE
measure: Cortical excitability (MEP; TMS)
timeFrame: BASELINE
measure: Cortical inhibition (SICI; TMS)
timeFrame: BASELINE
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre de Recherche Clinique (CRC) - CHSA
city: Paris
country: France
facility: Service Hospitalo-Universitaire (SHU) - CHSA
Study officials:
affiliation: CHSA
name: Isabelle Amado, Dr
role: STUDY_DIRECTOR
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Pavel Lindberg, PhD
role: STUDY_DIRECTOR
References:
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.
citation: 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.