A Pilot Open-label Trial of Individualized Repetitive Transcranial Magnetic Stimulation for Patients With Auditory Verbal Hallucinations
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Schizophrenia and Related Disorders
- Sponsor
- Columbia University
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- Total Number of Treatment Emergent Adverse Events
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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.
Investigators
Michael Avissar
Assistant Professor of Psychiatry
Columbia University
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
Outcomes
Primary Outcomes
Total Number of Treatment Emergent Adverse Events
Time Frame: 2 weeks.
The total number of treatment emergent adverse events. An emergent adverse event is defined as any rTMS risk induced incident in research such as headache and seizure.
Total Number of rTMS Sessions Completed
Time Frame: 2 weeks.
The total number of rTMS sessions completed. A session is defined as 20 minutes of rTMS. The outcome measure data comprises the cumulative count of all completed TMS sessions.
Secondary Outcomes
- Change in Psychotic Symptom Rating Scale (PSYRATS) - Delusion Symptoms(Baseline and 4 weeks)
- Change in Scale for the Assessment of Positive Symptoms (SAPS)- Delusions(Baseline and 4 weeks)
- Change in Positive and Negative Syndrome Scale (PANSS)- Negative Symptoms(Baseline and 4 weeks)
- Change in Psychotic Symptom Rating Scale (PSYRATS)- Auditory Hallucinations(Baseline and 4 weeks)
- Change in Scale for the Assessment of Positive Symptoms (SAPS)- Hallucinations(Baseline and 4 weeks)
- Change in Cardiff Anomalous Perceptions Scale (CAPS)(Baseline and 4 weeks)
- Change in Auditory Hallucination Rating Scale (AHRS)(Baseline and 4 weeks)
- Change in Positive and Negative Syndrome Scale (PANSS)- General Psychopathology(Baseline and 4 weeks)
- Change in Positive and Negative Syndrome Scale (PANSS)- Positive Symptoms(Baseline and 4 weeks)
- Number of Participants Withdrawn Resulting From a Change in Clinical Global Impression Improvement (CGI-I) Scale Score(Baseline and 2 weeks)
- Number of Participants Withdrawn Resulting From the Clinical Global Impression Severity (CGI-S) Scale Score(2 weeks)