An Extension Protocol for Patients Who Previously Completed the TMS Pilot Study

NCT05526833 | Terminated Results FDA Device

• 2 other identifiers: 8249K23MH119318
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia and Related Disorders

Keywords

Hallucinations; Auditory Verbal Hallucinations

Outcome Measures

Primary Outcomes (3)

• Total Number of rTMS Sessions Completed

  The total number of rTMS sessions completed for non responders and partial responders. A session is defined as 20 minutes of rTMS.

  2 weeks.

• Total Number of Follow-up Clinical Assessments Completed

  The total number of follow-up clinical assessments completed for complete responders. A clinical assessment refers to answering questions about psychiatric symptoms to assess the sustainability of the patient's improvement from the previous study.

  8 weeks

• Total Number of Treatment Emergent Adverse Events

  The total number of treatment emergent adverse events for non responders and partial responders. An emergent adverse event is defined as any rTMS risk induced incident in research such as headache and seizure.

  2 weeks.

Secondary Outcomes (7)

• Change in Auditory Hallucination Rating Scale (AHRS)

  Up to 4/8 weeks.

• Change in Psychotic Symptom Rating Scale (PSYRATS)

  Up to 4/8 weeks.

• Change in Scale for the Assessment of Positive Symptoms (SAPS)

  Up to 4/8 weeks.

• Change in Positive and Negative Syndrome Scale (PANSS)

  Up to 4/8 weeks.

• Change in Cardiff Anomalous Perceptions Scale (CAPS)

  Up to 4/8 weeks.

Study Arms (3)

Non-responders undergo rTMS of the right superior temporal sulcus (STS)

EXPERIMENTAL

Non-responders to protocol #8116 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 be administered 10 days (10 sessions) of MRI-guided 1 Hz rTMS delivered to the right superior temporal sulcus (STS). 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.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Partial responders undergo rTMS of the left temporo-parietal junction (TPJ)

EXPERIMENTAL

Partial responders to protocol #8116 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 be administered 10 days (10 sessions) of MRI-guided 1 Hz rTMS delivered to the original left temporo-parietal junction (TPJ) target. 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.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Complete responders undergo four follow-up clinical assessments

NO INTERVENTION

Complete responders to protocol #8116 will be offered followup clinical assessments at 1, 2, 4, and 8 weeks to assess sustainability of their response.

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

During the rTMS session, an electromagnetic coil is placed on the scalp of the subject's head. The electromagnet painlessly delivers a magnetic pulse that stimulates nerve cells in the region of the brain involved in speech perception.

Non-responders undergo rTMS of the right superior temporal sulcus (STS); Partial responders undergo rTMS of the left temporo-parietal junction (TPJ)

Eligibility Criteria

• Age: 22 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Columbia University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Schizophrenia; Hallucinations

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Limitations and Caveats

The study ended prematurely, resulting in a sample size that did not meet our expectations.

Results Point of Contact

• Title: Michael Avissar
• Organization: New York State Psychiatric Institute

MichaelAvissarMDPhD@gmail.com

(646) 774-5431

Study Officials

• Michael Avissar, MD, PhD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 31, 2022
• First Posted: September 2, 2022
• Study Start: September 12, 2022
• Primary Completion: January 24, 2023
• Study Completion: January 26, 2023
• Last Updated: February 16, 2024
• Results First Posted: February 16, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)