Clinical trial NCT05319080: Individualized Repetitive Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations
Official title: A Pilot Open-label Trial of Individualized Repetitive Transcranial Magnetic Stimulation for Patients With Auditory Verbal Hallucinations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Schizophrenia and Related Disorders
Keywords: Hallucinations
Auditory Verbal Hallucinations
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2022-04-08
Enrollment: 11
Sex: ALL
Minimum age (years): 22
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label study for participants with a diagnosis of either schizophrenia or schizoaffective disorder with persistent auditory verbal hallucinations (AVH) that are eligible to have repetitive transcranial magnetic stimulation (rTMS) targeting the left temporoparietal junction (TPJ).
Primary purpose: TREATMENT

Brief summary: The Repetitive Transcranial Magnetic Stimulation (rTMS) is a type of brain stimulation that uses a magnet to change activity in the brain. rTMS uses magnetic pulses to induce an electrical current in the brain to alter brain activity and function in specific areas. For example, stimulating the part of the brain controlling movement will cause parts of the foot or leg to twitch. TMS is proposed as a novel treatment for people with schizophrenia. The investigators want to see if low frequency rTMS can lessen some of the symptoms of schizophrenia, specifically auditory verbal hallucinations. Auditory verbal hallucinations describe the experience of hearing voices that are not really there.

Detailed description: The large majority of patients with schizophrenia (Sz) experience auditory verbal hallucinations (AVH) as a core feature of their disorder. Treatment-resistant auditory verbal hallucinations (AVH) affect a third of patients with schizophrenia and can cause increased aggression, distress, suicide, and social dysfunction. The current standard of care is antipsychotic medication which can cause metabolic syndrome, sedation, orthostatic hypotension, extrapyramidal symptoms, and tardive dyskinesia among other adverse effects. Transcranial magnetic stimulation (TMS) emits a rapidly changing magnetic field over the scalp which induces current flow in underling brain tissue, either enhancing or disrupting function depending on the frequency of stimulation. It is generally well tolerated and repetitive TMS (rTMS) is currently FDA approved for treatment of depression. rTMS carries potential as an alternative treatment for schizophrenia patients with AVH who either do not respond to or do not tolerate medication. Inhibitory (1-Hz) standard TMS approaches, which use scalp-based targeting of speech perception areas such as left temporoparietal junction (TPJ) have yielded mixed results in reducing AVH, possibly due to variability of underlying brain anatomy between individual subjects. The influence of anatomical variability could be eliminated by individually positioning the TMS coil according to each patient's structural brain MRI. The proposed pilot project will investigate the clinical efficacy of open-label individualized MRI-guided TMS applied to the left TPJ in ten patients with schizophrenia or schizoaffective disorder. If the results of the pilot study show promising reductions in AVH, it will set up the foundation for a larger sham-controlled clinical trial.

Eligibility criteria: Inclusion Criteria:

* The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder
* Capacity and willingness to provide informed consent
* Mean Auditory Hallucination Rating Scale (AHRS) item score of greater or equal to 2
* If female and not infertile, must agree to use one of the following forms of contraception for the duration of study participation: systemic hormonal treatment, an intrauterine device (IUD) which was implanted at least 2 months prior to screening, or "double-barrier" contraception. Women of child bearing potential must have a negative pregnancy test at screening
* Right handed
* Normal hearing
* Taking an antipsychotic medication at a stable dose for at least 4 weeks. All oral and depot antipsychotics are allowable.

Exclusion Criteria:

* Substance use disorder (excluding nicotine) within last 90 days, or positive toxicology screen for any substance of abuse
* Pregnancy
* Participation in study of investigational medication/device within 4 weeks
* History of seizure, epilepsy and neurologic conditions with structural cerebral damage, including stroke, multiple sclerosis, traumatic brain injury, Alzheimer's and other neurodegenerative diseases, meningoencephalitis or intracerebral abscess, parenchymal or leptomeningeal cancers, dementia, developmental disability, cerebrovascular disease, increased intracranial pressure, or central nervous system (CNS) tumors, brain surgery, head injury with loss of consciousness \>1 hour or clear cognitive sequelae, intracranial metal implants, known structural brain lesion
* Subjects with devices that may be affected by TMS (pacemaker, cardioverter defibrillator, medication pump, intracardiac line, cochlear implant, implanted brain stimulator/neurostimulator)
* Subjects with suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the Suicidal Ideation section of the baseline C-SSRS) in the 6 months prior to screening or subjects who represent a significant risk of suicide in the opinion of the investigator
* Frequent and persistent migraines
* Clinically significant skin disease
* Presence of unstable medical disorders, including those that are previously undiagnosed, untreated, inadequately treated, or active to an extent which might make participation hazardous. For example, hypertension, previous stroke, brain lesions, or heart disease
* History of prior clinically significant, adverse response to neurostimulation
* Current treatment with ototoxic medications (amino-glycosides, cisplatin)
* MRI incompatible implants
* Claustrophobia

Primary outcomes:
measure: Total Number of rTMS Sessions Completed
timeFrame: 2 weeks.
measure: Total Number of Treatment Emergent Adverse Events
timeFrame: 2 weeks.
Secondary outcomes:
measure: Change in Auditory Hallucination Rating Scale (AHRS)
timeFrame: Baseline and 4 weeks
measure: Change in Psychotic Symptom Rating Scale (PSYRATS)- Auditory Hallucinations
timeFrame: Baseline and 4 weeks
measure: Change in Psychotic Symptom Rating Scale (PSYRATS) - Delusion Symptoms
timeFrame: Baseline and 4 weeks
measure: Change in Scale for the Assessment of Positive Symptoms (SAPS)- Hallucinations
timeFrame: Baseline and 4 weeks
measure: Change in Scale for the Assessment of Positive Symptoms (SAPS)- Delusions
timeFrame: Baseline and 4 weeks
measure: Change in Positive and Negative Syndrome Scale (PANSS)- General Psychopathology
timeFrame: Baseline and 4 weeks
measure: Change in Positive and Negative Syndrome Scale (PANSS)- Positive Symptoms
timeFrame: Baseline and 4 weeks
measure: Change in Positive and Negative Syndrome Scale (PANSS)- Negative Symptoms
timeFrame: Baseline and 4 weeks
measure: Change in Cardiff Anomalous Perceptions Scale (CAPS)
timeFrame: Baseline and 4 weeks
measure: Number of Participants Withdrawn Resulting From a Change in Clinical Global Impression Improvement (CGI-I) Scale Score
timeFrame: Baseline and 2 weeks
measure: Number of Participants Withdrawn Resulting From the Clinical Global Impression Severity (CGI-S) Scale Score
timeFrame: 2 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
Study officials:
affiliation: New York State Psychiatric Institute
name: Michael Avissar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: