Clinical trial NCT06341517: Brain Circuitry Therapeutics for Schizophrenia
Official title: Brain Circuitry Therapeutics for Schizophrenia - A Cross-species Longitudinal Randomized Controlled Clinical Study to Treat Negative Symptoms of Schizophrenia Using Non-invasive Stimulation of the Cerebellum
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia; Psychosis
Lead sponsor: University of Geneva, Switzerland
Sponsor class: OTHER
Collaborators: name: University of Geneva, Switzerland
First posted: 2024-04-02
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This project is a double blind randomized clinical trials that examines the efficacy of cerebellar non invasive stimulation for apathy improvement in patients with schizophrenia

Detailed description: This double-blind RCT aims to explore the efficacy of intensiveTranscranial Magnetic Stimulation (TMS) in schizophrenia spectrum disorders. Previous studies in various disorders suggest that intensive TMS is efficacious and safe.

Participants will undergo neuronavigated intermittent theta burst TMS, targeted to individual network targets, at an accelerated protocol (multiple sessions a day), The primary goal is to determine the efficacy of this protocol in alleviating negative symptoms of schizophrenia.

Additionally, the study will measure the impact of accelerated TMS on a range of clinical and cognitive outcomes, along with neuroimaging markers indicative of symptom response.

Eligibility criteria: Inclusion Criteria:

* Inclusion criteria

  * Capable of giving informed consent as evaluated by the treating psychiatrist
  * Informed Consent signed by the subject
  * Patients aged 18 - 65 years diagnosed with a schizophrenia spectrum disorder (including schizophrenia, schizoaffective or non-organic psychosis, psychotic disorder NOS) according to DSM-5 criteria
  * Clinically stable condition judged by their treating psychiatrist
  * Background antipsychotic medication treatments have remained unchanged for at least 4 weeks
  * No hospitalization in acute psychiatry ward at least 3 months prior to study entry

Specific exclusion criteria related to psychopathology

* Comorbid and clinically active current major depressive episode determined by the treating psychiatrist.
* Active psychotic symptoms. In particular, patients that at Baseline have a PANSS scores of more than 4 in any of the following PANSS items: delusions, suspiciousness/persecution and hallucinatory behaviour will be considered not stable enough to participate.
* Significant extrapyramidal side-effects quantified by total score of mSAS \> 12.
* Increased sedation due to use of medication (slowing, drowsiness, slurred speech etc.)
* Active daily use of substances (i.e. cocaine), including for therapeutically medical purposes (e.g., methadone substitution)

Exclusion criteria related to MRI or TMS

* History of fainting spells of unknown or undetermined aetiology that might constitute seizures
* History of multiple seizures or diagnosis of epilepsy
* Any progressive (e.g., neurodegenerative) neurological disorder such as multiple sclerosis or Parkinson's disease
* Chronic uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
* Metallic objects/implants (excluding dental fillings) unless cleared to be MRI compatible (i.e. MRI compatible joint replacement)
* Any implants controlled by physiological signs in/near the head

  * Pacemaker
  * Implanted medication pump
  * Vagal nerve stimulator
  * Deep brain stimulator or TENS unit
  * Ventriculo-peritoneal shunt
  * Cochlear implant
* Impaired ability to sense heat/pain, open wounds etc.
* Increased intracranial pressure
* Intracranial lesion, from a known genetic disorder or from acquired neurologic disease (e.g. stroke, tumor, cerebral palsy, severe head injury, or significant dysmorphology).
* History of head injury resulting in prolonged loss of consciousness (\>15minutes) or neurological sequelae
* Ongoing pregnancy and breastfeeding. All participants capable of becoming pregnant will be required to have active contraception; any participant who is pregnant or breastfeeding will not be enrolled in the study.

Other exclusion criteria

* Clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, cancer, pulmonary decompensation etc.)
* Inability to follow the procedures of the investigation, e.g. due to language problems, psychological disorders, intellectual retardation, dementia, etc. of the subject
* Having legal obligation for psychiatric treatment.
* Participation in another investigation with an investigational drug or another MD within the 30 days preceding and during the present investigation.
* Previous enrolment into the current investigation
* Enrolment of the PI, his/her family members, employees and other dependent persons.

Primary outcomes:
measure: Brief Negative Symptoms Scale - apathy subscale (BNSS-Apathy) at follow-up (FU) at T3. The primary endpoint will be assessed at baseline and all follow-up visits at week 1, 6 and 12.
timeFrame: at 12 weeks
Secondary outcomes:
measure: Positive and Negative Symptoms Scale (PANSS) positive and negative subscores at follow-up
timeFrame: at 1 week
measure: Positive and Negative Symptoms Scale (PANSS) positive and negative subscores at follow-up
timeFrame: at 6 weeks
measure: Positive and Negative Symptoms Scale (PANSS) positive and negative subscores at follow-up
timeFrame: at 12 weeks
measure: Self reported Negative Scale SNS scores and its sub-scales at follow-up
timeFrame: at 1 week
measure: Self reported Negative Scale SNS scores and its sub-scales at follow-up
timeFrame: at 6 weeks
measure: Self reported Negative Scale SNS scores and its sub-scales at follow-up
timeFrame: at 12 weeks
measure: Brief neurocognitive assessment (BNA) scores at follow-up
timeFrame: at 6 weeks
measure: Auditory Hallucinations Rating Scale (AHRS) scores at follow-up
timeFrame: at 6 weeks
measure: Calgary Depression Scale (CDSS) scores at follow-up
timeFrame: at 6 weeks
measure: Young Mania Rating Scale (YMRS) scores at follow-up
timeFrame: at 6 weeks
measure: Personal and social performance scale (PSP) scores at follow-up
timeFrame: at 12 weeks
measure: Deep-phenotyping outcome - sEBR (spontaneous eye blink)
timeFrame: at 6 weeks
measure: Deep-phenotyping outcome - facial expressions
timeFrame: at 6 weeks
measure: Deep-phenotyping outcome - accelerometer
timeFrame: at 6 weeks
measure: Cerebellar-cortical functional connectivity
timeFrame: at 1 week
measure: Cerebellar-cortical structural connectivity
timeFrame: at 6 weeks
measure: Cerebellar-cortical structural connectivity
timeFrame: at 12 weeks
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Campus Biotech
city: Geneva
country: Switzerland
facility: Indrit Bègue
Study officials:
References: