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"Manual Dexterity and Oculomotor Control in Schizophrenia" (MADOCS)

C

Centre Hospitalier St Anne

Status

Unknown

Conditions

Schizophrenia

Treatments

Other: Neuropsychological evaluations
Device: TMS coupled to EMG recording
Other: Psychopathological evaluations
Device: Oculomotor movements
Device: Manual dexterity

Study type

Interventional

Funder types

Other

Identifiers

NCT02826629
D16-P01

Details and patient eligibility

About

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.

Full 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.

Enrollment

105 estimated patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

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:

    1. 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:

    1. 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)

Trial design

Primary purpose

Basic Science

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

105 participants in 4 patient groups

Schizophrenia
Other group
Description:
40 patients with diagnosis of schizophrenia (25 medicated - 15 non-medicated)
Treatment:
Device: TMS coupled to EMG recording
Other: Neuropsychological evaluations
Device: Oculomotor movements
Device: Manual dexterity
Other: Psychopathological evaluations
Healthy sibling
Other group
Description:
25 healthy siblings
Treatment:
Device: TMS coupled to EMG recording
Other: Neuropsychological evaluations
Device: Oculomotor movements
Device: Manual dexterity
Other: Psychopathological evaluations
Ultra high risk for developing Schizophrenia
Other group
Description:
15 patients with ultra high risk for developing Schizophrenia
Treatment:
Device: TMS coupled to EMG recording
Other: Neuropsychological evaluations
Device: Oculomotor movements
Device: Manual dexterity
Other: Psychopathological evaluations
Controls
Other group
Description:
-25 age and gender-matched healthy controls
Treatment:
Device: TMS coupled to EMG recording
Other: Neuropsychological evaluations
Device: Oculomotor movements
Device: Manual dexterity
Other: Psychopathological evaluations

Trial contacts and locations

2

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Central trial contact

Isabelle Amado, Dr; Marie GODARD

Data sourced from clinicaltrials.gov

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