Individualized Repetitive Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations

Schizophrenia and Related Disorders Clinical Trial

Official title:

A Pilot Open-label Trial of Individualized Repetitive Transcranial Magnetic Stimulation for Patients With Auditory Verbal Hallucinations

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05319080
• Other study ID #: 8116
• Secondary ID: K23MH119318
• Status: Terminated
• Phase: N/A
• Start date: August 1, 2022
• Est. completion date: April 7, 2023

Study information

• Verified date: March 2024
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: April 7, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Hallucinations
• Schizophrenia
• Schizophrenia and Related Disorders

Intervention

Device:
• Repetitive Transcranial Magnetic Stimulation (rTMS)
During the rTMS session, an electromagnetic coil is placed against the subjects scalp on the left side of the head. The electromagnet painlessly delivers a magnetic pulse that stimulates nerve cells in the region of the brain involved in speech perception.

Locations

Country	Name	City	State
United States	New York State Psychiatric Institute	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Number of rTMS Sessions Completed	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.	2 weeks.
Primary	Total Number of Treatment Emergent Adverse Events	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.	2 weeks.
Secondary	Change in Auditory Hallucination Rating Scale (AHRS)	The AHRS is an investigator-administered scale assessing multiple characteristics of auditory verbal hallucinations. The total score ranges from 2 to 41, with higher scores indicating more severe symptoms.	Baseline and 4 weeks
Secondary	Change in Psychotic Symptom Rating Scale (PSYRATS)- Auditory Hallucinations	The PSYRATS consists of 17 items on delusions and auditory hallucinations subscales, with each item being rated from 0 (absent) to 4 (severe). The score range for the auditory hallucinations subscale is 0-44 with a higher score indicating more severe auditory hallucinations.	Baseline and 4 weeks
Secondary	Change in Psychotic Symptom Rating Scale (PSYRATS) - Delusion Symptoms	The PSYRATS consists of 17 items on delusions and auditory hallucinations, with each item being rated from 0 (absent) to 4 (severe). The score range for the delusion subscale is 0-24 with a higher score indicating more delusion symptoms.	Baseline and 4 weeks
Secondary	Change in Scale for the Assessment of Positive Symptoms (SAPS)- Hallucinations	The SAPS includes 34 items that focus on the positive symptoms on schizophrenia. Each item is rated on a severity scale that ranges from 0 (none) to 5 (severe). The hallucination subscale scores range from 0-35 with a higher score indicating more severe hallucinations.	Baseline and 4 weeks
Secondary	Change in Scale for the Assessment of Positive Symptoms (SAPS)- Delusions	The SAPS includes 34 items that focus on the positive symptoms on schizophrenia. Each item is rated on a severity scale that ranges from 0 (none) to 5 (severe). The delusion subscale has a range from 0-65 with a higher score indicating more severe delusion symptoms.	Baseline and 4 weeks
Secondary	Change in Positive and Negative Syndrome Scale (PANSS)- General Psychopathology	The PANSS rates the presence and severity of positive and negative symptoms, as well as general psychopathology associated with schizophrenia. The general psychopathology subscale is a measure of deficits in cognition with scores ranging from 16-112. Higher scores indicate more severe symptoms.	Baseline and 4 weeks
Secondary	Change in Positive and Negative Syndrome Scale (PANSS)- Positive Symptoms	The PANSS rates the presence and severity of positive and negative symptoms, as well as general psychopathology associated with schizophrenia. Positive symptoms defined as a symptom of schizophrenia that represents an excess or distortion of normal function, as distinct from a deficiency in or lack of normal function (compare negative symptom). Positive symptoms include delusions or hallucinations, disorganized behavior, and manifest conceptual disorganization. Positive symptom subscale ranges from 7-49 with a higher score indicating more severe symptoms.	Baseline and 4 weeks
Secondary	Change in Positive and Negative Syndrome Scale (PANSS)- Negative Symptoms	The PANSS rates the presence and severity of positive and negative symptoms, as well as general psychopathology associated with schizophrenia. Negative symptoms defined as a deficit in the ability to perform the normal functions of living-for example, logical thinking, self-care, social interaction, and planning, initiating, and carrying out constructive actions-as shown in apathy, blunted affect, emotional withdrawal, poor rapport, and lack of spontaneity. The negative symptoms sub scale scores range from 7-49 with a higher score indicating more severe symptoms.	Baseline and 4 weeks
Secondary	Change in Cardiff Anomalous Perceptions Scale (CAPS)	The CAPS is a 32 item scale for measuring perceptual anomalies, that includes subscales for measuring distress, intrusiveness and frequency. A higher score indicates a higher number of perceptual anomalies, total scores range from 0 (low) to 32 (high).	Baseline and 4 weeks
Secondary	Number of Participants Withdrawn Resulting From a Change in Clinical Global Impression Improvement (CGI-I) Scale Score	The CGI-I is a clinician-rated scale to quantify overall clinician impression of improvements in level of illness.The CGI-I is rated on a 7-point scale, to assess illness improvement. CGI-I scores range from 1 (very much improved) through to 7 (very much worse). The scale is used as a safety stop in this study. A worsening in CGI-I score of 2 or greater from baseline for two consecutive days results in withdrawal of the participant from the study.	Baseline and 2 weeks
Secondary	Number of Participants Withdrawn Resulting From the Clinical Global Impression Severity (CGI-S) Scale Score	The CGI-S is a clinician-rated scale to quantify overall clinician impression of illness severity. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). The scale is used as a safety stop in this study. A score of 6 or 7 at the two week timepoint results in withdrawal of the participant from the study.	2 weeks