Clinical trial NCT05526833: An Extension Protocol for Patients Who Previously Completed the TMS Pilot Study
Official title: An Open-label Extension Trial of Individualized Repetitive Transcranial Magnetic Stimulation in Patients With Auditory Verbal Hallucinations Who Completed Protocol #8116
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: 2022-09-02
Enrollment: 3
Sex: ALL
Minimum age (years): 22
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Schizophrenia patients with AVH who have completed protocol #8116 will be recruited, and allocated to one of three arms based on their treatment responsiveness from protocol #8116 which included 10 low-frequency TMS treatment sessions using the TPJ target. Their treatment responsiveness is assessed by the Auditory Hallucination Rating Scale (AHRS) at pre- and post-TMS session. Non-responders will be offered 10 daily sessions of 1-Hz rTMS delivered to the rSTS region instead. Partial responders will be offered 10 additional daily sessions of 1-Hz rTMS delivered to the same original left TPJ target used in protocol #8116. Full responders will be offered followup clinical assessments at 1,2,4, and 8 weeks to assess sustainability of their response.
Primary purpose: TREATMENT

Brief summary: This is an open-label extension study to continue to evaluate the safety, tolerability and efficacy of the Repetitive Transcranial Magnetic Stimulation (rTMS) in subjects with schizophrenia or schizoaffective disorder who previously completed the treatment study of the protocol #8116 (NCT05319080). Protocol #8116 investigates the clinical efficacy of open-label individualized MRI-guided TMS applied to the left temporoparietal junction (TPJ) in schizophrenia patients. Participating patients who have completed the 4-week project #8116 can be screened for eligibility for this extension study in which they will continue treatment/assessment. They will be divided into three groups (non-responders, partial responders, or full responders) based on a reduction in the Auditory Hallucination Rating Scale (AHRS) scores from the study #8116.

Detailed description: The optimal neuroanatomical treatment targets remain unclear, though current neuroscience evidence suggests several brain areas such as the left temporo-parietal junction area (TPJ) or the right posterior superior temporal sulcus (rSTS) may be involved in the generation and development of AVH. During this extension study, non-responders to protocol #8116 will be administered 10 days (10 sessions) of MRI-guided 1 Hz rTMS delivered to the rSTS instead of the original target in TPJ. Partial responders will receive 10 additional low-frequency rTMS over the original left TPJ target. Like the protocol #8116, the investigators will use the MRI-guided targeting approach during rTMS treatment sessions to achieve greater precision as it can account for individual differences in anatomy. Complete responders will instead be followed for sustainability of response. Their clinical ratings will be repeated at one week, two week, four week and eight week follow-ups. Non-responders are defined as patients showing a reduction of AHRS less than 20% of the initial score. A partial response is defined as a reduction in a range of between 20% and 50% of the initial AHRS score. A complete response is defined as a reduction by at least 50% of the initial AHRS score.The combined outcome of protocol #8116 and the currently proposed protocol will help guide TMS targeting and the number of treatment sessions for a future larger randomized, double-blinded, shame-controlled clinical trial.

Eligibility criteria: For non responders and partial responders:

Inclusion Criteria:

* Completion of the study #8116 (NCT05319080)
* The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder
* A reduction of AHRS less than 50% of the initial score
* Capacity and willingness to provide informed consent
* 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
* Severe adverse events of TMS
* 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)

For complete responders:

Inclusion Criteria:

* Completion of the study #8116 (NCT05319080)
* The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder
* A reduction by at least 50% of the initial AHRS score
* 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
* 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
* Presence or positive history of unstable significant medical or neurological illness

Primary outcomes:
measure: Total Number of rTMS Sessions Completed
timeFrame: 2 weeks.
measure: Total Number of Follow-up Clinical Assessments Completed
timeFrame: 8 weeks
measure: Total Number of Treatment Emergent Adverse Events
timeFrame: 2 weeks.
Secondary outcomes:
measure: Change in Auditory Hallucination Rating Scale (AHRS)
timeFrame: Up to 4/8 weeks.
measure: Change in Psychotic Symptom Rating Scale (PSYRATS)
timeFrame: Up to 4/8 weeks.
measure: Change in Scale for the Assessment of Positive Symptoms (SAPS)
timeFrame: Up to 4/8 weeks.
measure: Change in Positive and Negative Syndrome Scale (PANSS)
timeFrame: Up to 4/8 weeks.
measure: Change in Cardiff Anomalous Perceptions Scale (CAPS)
timeFrame: Up to 4/8 weeks.
measure: Change in Clinical Global Impression Improvement (CGI-I) Scale
timeFrame: 2 weeks
measure: Change in Clinical Global Impression Severity (CGI-S) Scale
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: