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

Overview

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.

Interventions

• Device iTBS
  Intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses for up to 8 sessions daily for 5 days

Primary outcome measures

• 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. [Time frame: at 12 weeks]

Secondary outcome measures (12)

• Positive and Negative Symptoms Scale (PANSS) positive and negative subscores at follow-up [Time frame: at 1 week]
• Positive and Negative Symptoms Scale (PANSS) positive and negative subscores at follow-up [Time frame: at 6 weeks]
• Positive and Negative Symptoms Scale (PANSS) positive and negative subscores at follow-up [Time frame: at 12 weeks]
• Self reported Negative Scale SNS scores and its sub-scales at follow-up [Time frame: at 1 week]
• Self reported Negative Scale SNS scores and its sub-scales at follow-up [Time frame: at 6 weeks]
• Self reported Negative Scale SNS scores and its sub-scales at follow-up [Time frame: at 12 weeks]
• Brief neurocognitive assessment (BNA) scores at follow-up [Time frame: at 6 weeks]
• Auditory Hallucinations Rating Scale (AHRS) scores at follow-up [Time frame: at 6 weeks]
• Calgary Depression Scale (CDSS) scores at follow-up [Time frame: at 6 weeks]
• Young Mania Rating Scale (YMRS) scores at follow-up [Time frame: at 6 weeks]
• Personal and social performance scale (PSP) scores at follow-up [Time frame: at 12 weeks]
• Deep-phenotyping outcome - sEBR (spontaneous eye blink) [Time frame: at 6 weeks]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Switzerland · 2 centers

• Campus Biotech — Geneva
• Indrit Bègue — Geneva

Identifiers

NCT: NCT06341517 · BASEC-ID:2023-D0117

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗