Back to resultsIndividualized Repetitive Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations
Primary Purpose
Schizophrenia and Related Disorders
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Repetitive Transcranial Magnetic Stimulation (rTMS)
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia and Related Disorders focused on measuring Hallucinations, Auditory Verbal Hallucinations
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 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
Sites / Locations
- New York State Psychiatric Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Individualized magnetic resonance imaging (MRI) guided rTMS
Arm Description
Participants will receive a type of TMS called repetitive TMS (rTMS) wherein the magnetic pulses delivered will be close together in a rapid sequence. They will receive a 20-min once-daily rTMS sessions over a period of 2 weeks (weekends off), and therefore accrue a total of 10 rTMS stimulation sessions. The rTMS parameters that will be used are a frequency of 1 Hz (1 pulse per second) at an intensity of 90% of the motor threshold (MT). Therefore, the investigators will deliver 1200 continuous pulses per session/day which adds up to 12,000 pulses in total for the whole treatment.
Outcomes
Primary Outcome Measures
Total number of rTMS sessions completed
The total number of rTMS sessions completed. A session is defined as 20 minutes of rTMS.
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.
Secondary Outcome Measures
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.
Change in Psychotic Symptom Rating Scale (PSYRATS)
The PSYRATS consists of 17 items on delusions and auditory hallucinations, with each item being rated from 0 (absent) to 4 (severe).
Change in Scale for the Assessment of Positive Symptoms (SAPS)
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).
Change in Positive and Negative Syndrome Scale (PANSS)
The PANSS rates the presence and severity of positive and negative symptoms, as well as general psychopathology associated with schizophrenia. Each item is rated from 1 to 7 (range=30-210). Higher scores indicate more severe symptoms.
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, scores range from 0 (low) to 32 (high).
Change in Clinical Global Impression Improvement (CGI-I) Scale
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).
Change in Clinical Global Impression Severity (CGI-S) Scale
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05319080
Brief Title
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
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
August 1, 2022 (Actual)
Primary Completion Date
March 31, 2023 (Actual)
Study Completion Date
April 7, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Columbia University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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 temperoparietal 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia and Related Disorders
Keywords
Hallucinations, Auditory Verbal Hallucinations
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
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 temperoparietal junction (TPJ).
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Individualized magnetic resonance imaging (MRI) guided rTMS
Arm Type
Experimental
Arm Description
Participants will receive a type of TMS called repetitive TMS (rTMS) wherein the magnetic pulses delivered will be close together in a rapid sequence. They will receive a 20-min once-daily rTMS sessions over a period of 2 weeks (weekends off), and therefore accrue a total of 10 rTMS stimulation sessions. The rTMS parameters that will be used are a frequency of 1 Hz (1 pulse per second) at an intensity of 90% of the motor threshold (MT). Therefore, the investigators will deliver 1200 continuous pulses per session/day which adds up to 12,000 pulses in total for the whole treatment.
Intervention Type
Device
Intervention Name(s)
Repetitive Transcranial Magnetic Stimulation (rTMS)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Total number of rTMS sessions completed
Description
The total number of rTMS sessions completed. A session is defined as 20 minutes of rTMS.
Time Frame
2 weeks.
Title
Total number of treatment emergent adverse events
Description
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.
Time Frame
2 weeks.
Secondary Outcome Measure Information:
Title
Change in Auditory Hallucination Rating Scale (AHRS)
Description
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.
Time Frame
Up to 4 weeks.
Title
Change in Psychotic Symptom Rating Scale (PSYRATS)
Description
The PSYRATS consists of 17 items on delusions and auditory hallucinations, with each item being rated from 0 (absent) to 4 (severe).
Time Frame
Up to 4 weeks.
Title
Change in Scale for the Assessment of Positive Symptoms (SAPS)
Description
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).
Time Frame
Up to 4 weeks.
Title
Change in Positive and Negative Syndrome Scale (PANSS)
Description
The PANSS rates the presence and severity of positive and negative symptoms, as well as general psychopathology associated with schizophrenia. Each item is rated from 1 to 7 (range=30-210). Higher scores indicate more severe symptoms.
Time Frame
Up to 4 weeks.
Title
Change in Cardiff Anomalous Perceptions Scale (CAPS)
Description
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, scores range from 0 (low) to 32 (high).
Time Frame
Up to 4 weeks.
Title
Change in Clinical Global Impression Improvement (CGI-I) Scale
Description
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).
Time Frame
2 weeks
Title
Change in Clinical Global Impression Severity (CGI-S) Scale
Description
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).
Time Frame
2 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
22 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Avissar, MD, PhD
Organizational Affiliation
New York State Psychiatric Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York State Psychiatric Institute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Individualized Repetitive Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations
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