Treating Social Cognition With Theta Burst Stimulation; a Pilot Sudy (PilotTMS-COG)

Treating Social Cognition Impairments in Patients With Schizophrenia With Repetitive Transcranial Magnetic Stimulation (Theta-Burst; TBS); a Pilot Study

The purpose of the study is to test a new treatment of social cognition deficits in patients with schizophrenia or schizoaffective disorder by transcranial magnetic stimulation (theta-burst). The study will also identify clinical variables, cognitive and psychomotor most sensitive to treatment, to estimate the most sensitive treatment target, assess tolerance, to assess the impact of repetitive Transcranial Magnetic Stimulation (rTMS) on the brain a multimodal imaging study and compare the imaging variables (resting network, Diffusion Tensor Imaging, magnetic resonance spectroscopic imaging; MRSI) between patients before treatment and healthy subjects.

Study Overview

• Status: Unknown
• Conditions: Social Cognition in Patients With Schizophrenia
• Intervention / Treatment: Device: Active TBS; Device: Sham TBS

Detailed Description

The language understanding of other people is based on linguistic decoding mechanisms (phonological, semantic, syntactic ...) but also more on subtle mechanisms for the recognition of emotions and intentions. Interact with another one requires understanding its language but also to infer emotions and intentions. There are patients with schizophrenia suffering from social cognition disorders that impair social interactions; These patients often have difficulty in extracting the non-verbal emotional content of language and have difficulty inferring the thoughts and intentions of others. Recently, we have suggested a link between such deficits and the hypofunction of the medial prefrontal cortex.

Transcranial magnetic stimulation is a noninvasive neuromodulation technique that increases or decreases the focal cortical excitability depending on stimulation parameters. This technique is now commonly used as a therapeutic tool. It has been tried with some success in patients with schizophrenia in some indications:

• To reduce the auditory verbal hallucinations stimulating the temporal cortex
• More rarely, to reduce the negative symptoms stimulating the dorsolateral prefrontal cortex So far, the medial prefrontal cortex was not considered as a possible target as the scalp to cortex distance prevent from using conventional stimulation coils. Recently new coils have been developed that permit stimulation of deeper cortical regions.

We hypothesize that the use of transcranial magnetic stimulation with a theta burst intermittent protocol known to increase the cortical excitability and aiming the medial prefrontal cortex with a special antenna will improve social interaction capabilities of schizophrenic patients.

This ambitious and innovative assumption shall be first supported by a study of feasibility which is the subject of this trial.

Moreover, changes in the anatomical and functional connectivity, in brain metabolism and in cortical excitability will be observed after stimulation thanks to a multimodal imaging and the study of P50 wave.

In this pilot study, involving 20 patients, we plan to assess the social cognition deficits before and after 10 sessions of magnetic stimulation (2 sessions per day for 5 consecutive days) using a neuronavigation system and Magstim® stimulator. In order to assess the feasibility and specificity of the stimulation of medial prefrontal cortex (MPC), the effects of this treatment will be compared to the effects of the same treatment aiming the dorsolateral prefrontal cortex (DLPFC), also involved in aspects of negative symptoms of schizophrenia, and placebo effects induced by sham stimulation (using a sham coil). The recording of the P50 wave will be just before and after the 1st session and just after the last stimulation session. An MRI anatomical, functional and spectroscopic be performed before and 30 days after the treatment. A control group of twenty healthy subjects will perform the same MRI acquisitions.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Clement Nathou, MD; Phone Number: +33 (0)231065018; Email: nathou@chu-caen.fr
• Study Contact Backup: Name: Sonia Dollfus, MD, PhD; Phone Number: +33 (0)231065018; Email: dollfus@chu-caen.fr

Study Locations

• France
  • Caen, France, 14033
    • Recruiting
    • CHU de Caen - Centre Esquirol
    • Contact: Clément Nathou, Dr.; Phone Number: +33231065018; Email: nathou-c@chu-caen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• with a diagnosis of schizophrenia or schizoaffective disorder (DSM-IV MINI R)
• less than 20 years of disease duration
• Having signed a written informed consent
• LIS score > 15 or negative PANSS score > 15

Exclusion Criteria:

• Any change in psychotropic drugs (antidepressants, antipsychotics or mood stabilizers) during the two months preceding the inclusion
• Pregnant or breastfeeding women
• Subjects with a neurological condition or with epilepsy
• Subjects with a counter-indication to MRI or Transcranial stimulation (electronic or metal implants)
• Subjects that refuse to wear earplugs during MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Healthy subjects; Multimodal imaging data acquisitions Clinical data acquisitions
Experimental: TBS-MPC; Intervention with active TBS aiming Medial Prefrontal Cortex in 6 patients with schizophrenia; Baseline: Multimodal imaging data acquisitions; Clinical data acquisitions; P50 acquisition; Endpoint: Multimodal imaging data acquisitions; Clinical data acquisitions; P50 acquisition; Continuous actimetry acquisition	Device: Active TBS; Non-invasive transcranial magnetic stimulation inducing changes in cortical excitability depending on the cortical target (except for sham stimulation)
Active Comparator: TBS-CPDLF; Intervention with active TBS aiming Dorsolateral Prefrontal Cortex in 6 patients with schizophrenia; Baseline: Multimodal imaging data acquisitions; Clinical data acquisitions; P50 acquisition; Endpoint: Multimodal imaging data acquisitions; Clinical data acquisitions; P50 acquisition; Continuous actimetry acquisition	Device: Active TBS; Non-invasive transcranial magnetic stimulation inducing changes in cortical excitability depending on the cortical target (except for sham stimulation)
Sham Comparator: TBS-Sham; Intervention with Sham TBS in 8 patients with schizophrenia; Baseline: Multimodal imaging data acquisitions; Clinical data acquisitions; P50 acquisition; Endpoint: Multimodal imaging data acquisitions; Clinical data acquisitions; P50 acquisition; Continuous actimetry acquisition	Device: Sham TBS; Sham stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
V-LIS total score	change from baseline in V-LIS total score compared to 30 days after the end of the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GLX ratio	GLX (= Glutamine + Glutamate) ratio are measured in the DLPFC and in the MPC	change in baseline GLX ratio measured in MRSI compared to 30 days after the end of the treatment
P50 wave amplitude		change in baseline P50 amplitude compared to immediately after the end of the treatment
Motor activity		change in baseline motor activity measured with an actimeter compared to 30 days after the end of the treatment

Collaborators and Investigators

• Sponsor: University Hospital, Caen
• Investigators: Principal Investigator: Clément Nathou, MD, University Hospital, Caen

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: May 4, 2015
• First Submitted That Met QC Criteria: May 7, 2015
• First Posted (Estimate): May 12, 2015

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 19, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Schizophrenia; Social Cognition; transcranial magnetic stimulation; MRSI; theta burst stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 2014-A00839-38