Clinical trial NCT03483909: Transcranial Magnetic Stimulation to Improve Gesture Control
Official title: Repetitive Transcranial Magnetic Stimulation (rTMS) to Improve Gesture Control in Schizophrenia: A Randomised, Placebo-controlled, Double-blind Crossover Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Schizophrenia and Related Disorders
Keywords: gesture
rTMS
nonverbal communication
schizophrenia
psychosis
Lead sponsor: University of Bern
Sponsor class: OTHER
First posted: 2018-03-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: randomized, double-blind, cross-over trial of 3 rTMS protocols
Primary purpose: TREATMENT

Brief summary: The majority of schizophrenia patients is impaired in hand gesture performance, which contributes to poor functional outcome and poor communication skills. The left inferior frontal gyrus (IFG) and the left inferior parietal lobe (IPL) are key nodes of the gesture network, which is less active in patients with schizophrenia. Here, the investigators test single sessions of rTMS/TBS known to either enhance or inhibit local brain activity for app. 1 hour. The investigators aim to determine, which protocol may improve gesture performance in patients and healthy controls. This is a randomized, double-blind, cross-over, placebo-controlled single-center trial in 20 patients with schizophrenia spectrum disorders and 20 healthy controls. Gesture performance will be tested immediately after each TMS session, which are separated by 48 hours. Results of this study will inform larger interventional trials comparing 2 TMS protocols with repeated administration.

Detailed description: Schizophrenia is associated with poor social functioning, which is perturbed by deficits in social interaction including nonverbal communication. The use of hand gestures is critical for nonverbal communication, but the majority of schizophrenia patients has severe gesture impairments. Today no intervention may ameliorate gesture impairments. Patients with gesture impairments have altered structure and function of the gesture network, particularly the left inferior frontal gyrus (IFG) and also the left inferior parietal lobe (IPL). Noninvasive brain stimulation techniques may alter local brain function. Repetitive transcranial magnetic stimulation (rTMS) and particularly theta burst stimulation (TBS) for a few mins is a very safe method to alter brain states locally for approximately 1 hour. Indeed, facilitatory stimulation of the left frontal cortex by transcranial direct current stimulation (tDCS) demonstrated improved gesture perception and interpretation in healthy subjects. In addition, inhibitory stimulation with continuous theta burst stimulation (cTBS) over left IFG may perturb gesture performance in healthy subjects. Thus, the investigators hypothesize that local changes of brain activity within the gesture network would change gesture performance. Particularly, facilitatory intermittent theta burst stimulation (iTBS) of the left IFG would improve gesture performance. The investigators will test single sessions of rTMS in healthy subjects and schizophrenia patients. If one of the protocols proves to have superior effects, this result will help to plan interventional trials targeting social interaction deficits in schizophrenia. The aim of the study is to determine the effect of one session of iTBS over the left IFG on gesture performance compared to cTBS over the right IPL (active comparator) and one placebo rTMS sessions. This is a randomized, double-blind, cross-over, placebo-controlled single-center trial in 20 patients with schizophrenia spectrum disorders and 20 healthy controls. After baseline assessment of gesture performance, participants will receive one rTMS protocol at each time point, immediately followed by assessments of gesture performance and dexterity. rTMS sessions will be separated by 48 hours. Gesture performance will be measured with video recorded Test of Upper Limb Apraxia, which is rated blindly according to a manual.

Eligibility criteria: Inclusion Criteria:

* Right handed according to the Edinburgh Handedness Inventory
* Ability and willingness to participate in the study
* Ability to provide written informed consent
* Informed Consent as documented by signature (Appendix Informed Consent Form)
* Spent majority of childhood/adolescence in Switzerland
* Patients: schizophrenia spectrum disorder according to Diagnostic and Statistical Manual version 5 (DSM-5)

Exclusion Criteria:

* Women who are pregnant or breast feeding
* Metal objects on or in the body (e.g. grenade splinter, cardiac pacemaker, vessel clips, metal prostheses, contraceptive coil, cochlear implants, hearing aid, tooth implant)
* History of neurosurgery, any severe head wounds, history of neurologic disorders impacting gesture, e.g. Parkinson's disease, stroke, multiple sclerosis sclerosis and epilepsy, convulsion or seizure
* History of any hearing problems or ringing in the ears.
* Active drug addiction except nicotine
* Controls: first-degree relatives with schizophrenia spectrum disorders

Primary outcomes:
measure: Test of Upper Limb Apraxia
timeFrame: 10 mins after baseline assessment
measure: Test of Upper Limb Apraxia
timeFrame: 10 mins after left IFG iTBS
measure: Test of Upper Limb Apraxia
timeFrame: 10 mins after right IPL cTBS
measure: Test of Upper Limb Apraxia
timeFrame: 10 min after placebo stimulation
Secondary outcomes:
measure: Coin rotation
timeFrame: 20 min after baseline assessment
measure: Coin rotation
timeFrame: 20 min after left IFG iTBS
measure: Coin rotation
timeFrame: 20 min after right IPL cTBS
measure: Coin rotation
timeFrame: 20 min after placebo stimulation
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: University Hospital of Psychiatry
Study officials:
affiliation: University of Bern, University Hospital of Psychiatry
name: Sebastian Walther, MD
role: PRINCIPAL_INVESTIGATOR
References: